Douglas Alan Marchuk
Professor of Molecular Genetics and Microbiology
Vascular Morphogenesis: A Human Genetics Approach
Advances in our understanding of fundamental biological events can often be made by the analysis of defects manifested in inherited diseases. The genes responsible for these genetic syndromes often encode proteins that act at critical points of the pathways that control fundamental biological processes such as cell division, differentiation, and cell death. This approach has lead to the discovery of novel gene products and/or biochemical pathways involved in disease, genes that in turn play a fundamental role in normal biological processes.
My laboratory has taken this genetic approach for the study of angiogenesis, beginning with Mendelian disorders of vascular dysplasia and progressing to more complex vascular phenotypes. Our objectives are twofold: (1) to gain specific knowledge of the pathology observed in these disorders, and (2) to provide basic knowledge on the role of these genes and gene products in angiogenesis. The first step is to identify the genetic loci that underlie these syndromes. These mapping and positional cloning endeavors become the basis for future molecular biological studies on the role of the mutant gene products in the pathology of the disease, and the role of the normal proteins in vascular development. In order to investigate disease mechanism and pathogenesis, we then create an appropriate transgenic or knockout mouse as an animal model of the disease. The animal model serves both as a tool to further understand the pathophysiology of the disease, and a more tractable system to begin to identify other factors (genetic and environmental) that may alter the phenotype. Coming full circle, we can determine if the factors identified in the animal model also modify the clinical phenotype in the human disease. We currently have four projects that utilize this approach, and a new initiative that begins with a mouse model of hypertrophic cardiomyopathy.
Project 1. Molecular Genetics of Arterio-Venous Communication: Hereditary Hemorrhagic Telangiectasia: Hereditary Hemorrhagic Telangiectasia (HHT or Osler-Weber-Rendu disease) is an autosomal dominant disorder characterized by hemorrhagic stroke, gastrointestinal bleeding, and other vascular pathology. The clinical features result from the development of focal vascular malformations characterized by direct arteriovenous shunts with a loss of the capillary beds. The pathology of this disorder suggests a critical role for the HHT gene(s) in vascular development and angiogenesis of the capillary bed. However, until our work on this disorder, the nature of the molecular defect remained unknown. We have shown that HHT is actually a group of related disorders with overlapping but distinct phenotypes and genetic etiologies (McAllister et al., 1994a; Porteous et al., 1994; Berg et al., 1996). We established genetic linkage at two distinct loci for HHT, one on chromosome 9q33 (McDonald et al., 1994) and the other on 12q13 (Johnson DW, et al., 1995). We subsequently identified the gene for HHT 1 as endoglin (McAllister et al., 1994b), a transforming growth factor-ÿ(TGF-ÿÿ) binding protein of endothelial cells, and the HHT 2 locus as the activin-like kinase receptor, ALK-1, which has sequence homology to type I TGF-ÿÿ receptors (Johnson et al., 1996). Expression analyses of the mutant allele for endoglin (McAllister et al., 1995; Gallione et al., 1998) and for ALK-1 (Berg et al., 1997; Klaus et al., 1998) has shown that most alleles lead to unstable message or reduced levels of protein, suggesting inherited haploinsufficiency. These data suggest a critical role for the TGF-ÿÿ signal transduction pathway in the pathology of this disease, and more significantly, in the development and/or repair of blood vessels.
Our research has more recently involved a combination of genetic and molecular biological approaches to further study the role of ALK-1 and endoglin in cardiovascular disease and angiogenesis. We are investigating whether sequence polymorphisms in the endoglin and/or ALK-1 genes are risk factors for cerebrovascular disease in the general population with retrospective case-control association studies. We have already shown that one sequence polymorphism in endoglin is associated with increased risk for hemorrhagic stroke (Alberts et al., 1997), an observation which has now been replicated by others in the Japanese population (Takenaka et al., 1999). We are currently attempting to understand how this intronic polymorphism may affect RNA splicing or message stability. Three endoglin coding-polymorphisms are also under investigation, as the intronic polymorphism may be in linkage disequilibrium with one of these.
Although both endoglin and ALK-1 share sequence homology to the TGF-ÿ family of receptors, little is known about their precise role in signaling. Due to the lack of a signaling assay for ALK-1, there is no evidence other than sequence homology that ALK-1 is a TGF-ÿ receptor. We created a signaling assay for ALK-1 by constructing a chimeric receptor consisting of the extracellular ligand-binding domain of ALK-1 fused to the kinase domain of the TGF-ÿ receptor TÿRI, which can activate a reporter gene driven by the PAI-1 promoter. Using this chimera, we have demonstrated ligand specific activation for TGF-ÿ1, -ÿÿ3 (but not -ÿÿ2), and an additional uncharacterized ligand present in serum (Lux et al., 1999). Significantly, this ligand specificity for the TGF-ÿ isoforms parallels that of endoglin. We have also shown that ALK-1 and endoglin can be immunoprecipitated together in a receptor complex (Lux et al., 1999), suggesting that HHT is a result of altered signaling via an endothelial-specific TGF-ÿ receptor complex.
We have used this signaling assay to attempt to identify the novel ligand present in serum. Results with all available mammalian TGF-ÿ family members were negative (Lux et al., 1999). The Drosophila SAX gene encodes a receptor which may be the most similar in this species to mammalian ALK-1. We have now shown that the Drosophila SAX ligand screw (SCW) activates the ALK-1 chimera in our assay (Lux, Arora, and Marchuk, unpublished). The reciprocal experiment, performed in the laboratory of our collaborator Kavita Arora (UC, Irvine) suggests that mammalian ALK-1 can partially substitute for SCW in Drosophila development. The combined data suggest that ALK-1 signaling may involve a novel TGF-ÿ related ligand, and that a novel biochemical pathway involved in fundamental angiogenic processes awaits identification. Attempts to clone the mammalian homologue of the SCW ligand are in progress, using a variety of bioinformatic, molecular and biochemical approaches. Using our signaling assay, we are attempting to identify the downstream effectors of this pathway, as well as characterize the changes in gene expression due to signaling through these receptors.
We also wish to create animal models for HHT1 and 2. We now have ALK-1 and endoglin knockout mice. Although in both cases the mutant homozygotes show embryonic lethality, we have recently identified gastrointestinal vascular malformations (telangiectasias) in the ALK-1 heterozygotes (Yu, McLendon, and Marchuk, unpublished). The mice have become a critical resource for future studies on HHT, as will be outlined in the section on Future Directions.
Project 2. Molecular Genetics of Venous Angiogenesis: Familial Venous Malformations: Venous malformations are composed of large vascular lumens lined by a single-layered flat mature endothelium, which are thus prone to hemorrhage. The cutaneous and visceral lesions occur as single or multiple lesions with a nodular or tumor-like appearance. The presence of a few families exhibiting autosomal dominant inheritance of these vascular lesions suggested that genetic linkage analysis and positional cloning could be used to identify the responsible gene(s). We confirmed an earlier report by the laboratories of Bjorn Olsen and Matt Warman of linkage to chromosome 9p21 for autosomal dominant venous malformations (Gallione et al., 1995). We subsequently mapped the gene for the tie-2 receptor kinase to the candidate interval, and in collaboration with this group, identified an identical mutation in the kinase domain of tie-2 for two large kindreds (Vikkula et al., 1996). In our laboratory, we subsequently identified a second missense mutations in tie-2 which causes FVM, and have shown that both known mutations constitutively activate the receptor (Calvert et al., 1999). Although the tie-2/angiopoietin pathway has been implicated in vasculogenesis and embryonic angiogenesis from knockout studies in the mouse, our work suggests that this pathway has a role in the maintenance of proper vascular structure extending into adulthood. We speculate that this pathway is involved in endothelial-smooth muscle association based on the anatomy of the vascular lesion.
We are now creating a transgenic mouse model of this disorder, by expressing both tie-2 mutations under the control of its own promoter. This mouse model will be most useful for our understanding of the initiating event in lesion formation in these families, since although the phenotype is expressed in the heterozygous state, there appears to be no global vascular pathology outside of the vascular lesions themselves.
We have also identified 5 additional families with a clinical presentation similar to our tie-2 venous malformation families, but which exclude the tie-2 locus by linkage analysis. In some families the lesions were classified as glomangiomas, a benign tumor derived from the glomus cells (smooth muscle derivative) of the vasculature. We have recently shown that these families map to chromosome 1p (Calvert et al. submitted), and are actively searching for mutations in genes mapping to the critical region.
Project 3. Molecular Genetics of Cerebrovascular Angiogenesis: Cerebral Cavernous Malformations: Cerebral cavernous malformations (CCM) are congenital vascular anomalies of the brain comprising focal, thin-walled, grossly dilated vascular spaces. The lesions are responsible for significant neurologic disability, in particular, intractable migraine, seizures, and hemorrhagic stroke. Autosomal dominant forms of CCM have been described and we and others have shown that a gene for CCM (CCM1) maps to chromosome 7q (Marchuk et al., 1995). Taking advantage of a shared disease haplotype in Mexican-American families, we were able to narrow the critical region to under 500 kb (Johnson et al., 1995c; and unpublished data). We have now identified the CCM1 gene as KRIT1, a recently discovered binding partner of the Krev-1/rap1a tumor suppressor gene (Sahoo et al., in press). A common mutation in most Hispanic families (16 of 21 families analyzed) confirms the founder effect in this population. Other Hispanic and non-Hispanic families harbor different mutations, all of which appear to be null alleles. These data show the strength of this genetic approach to cardiovascular disease, as the Krev-1/rap1a signaling pathway, although implicated in cancer (e.g. Tuberous sclerosis), has not previously been shown to be required for angiogenesis, nor has it been previously implicated in any cardiovascular pathology. We are currently working to create a mouse model of CCM1, as well as to characterize the role of this biochemical pathway in the pathology of hemorrhagic stroke associated with CCM. Mutation analysis is already underway to determine the involvement of KRIT1 mutations/polymorphisms in common (non-hereditary) cerebral cavernous malformations.
Project 4. Molecular Genetics of Capillary Angiogenesis: Hemangiomas: Our work on the autosomal dominant vascular disorders has identified genes involved in the regulation of vascular growth. However, all of these germline mutations are compatible with normal vascular development. We also wish to identify novel genes that might be essential for vasculogenesis and embryonic angiogenesis. Such genes can in principle be identified using human phenotypes, by searching for somatic mutations underlying non-inherited vascular anomalies. We are using this approach to identify the gene(s) underlying the most common tumor (of any kind) in infancy - hemangiomas.
Hemangiomas are benign tumors consisting primarily of proliferating capillaries, which often occur as an elevated purple or red spot on the skin. Hemangiomas usually develop shortly after birth, but are self-limiting and go through a characteristic two-staged process of growth and regression. The rapid proliferation stage suggests an uncontrolled stage of angiogenesis. Our hypothesis is that hemangiomas arise from an early somatic mutation within a critical gene for capillary angiogenesis. Due to the localized nature of the tumor, our prediction is that the mutated gene products will be acting in a cell-autonomous nature, with the tumor resulting from a clonal expansion cell containing the original mutation. Using a clonality assay based on non-random X-chromosome inactivation, we have shown that most proliferative hemangiomas appear mono-clonal (Walter and Marchuk, in preparation). We have also shown significant loss of heterozygosity for markers on chromosome 5q (Berg et al., in press), in the same region that we have identified a genetic susceptibility locus (see below). We are currently searching for mutations in the genes involved in the vascular endothelial growth factor (VEGF) pathway.
Although the great majority of hemangiomas occur sporadically, we have identified a number of families displaying autosomal dominant segregation of childhood hemangiomas (Blei et al., 1998). Using these families to identify genetic loci that may predispose children to hemangioma development, we have found linkage to a region on distal chromosome 5q (Walter et al., 1999). We hope that these independent lines of analysis will converge as we discover that some of these genetic loci are involved in both familial and sporadic cases, the mutations being inherited in the familial cases and acquired somatically in the sporadic cases.
Project 5. Molecular Genetics of Hypertrophic Cardiomyopathy: A Mouse Model of Heart Failure: Heart failure is a common cause of mortality in the United States. It is the final outcome of a variety of conditions, both primary and secondary, that affect the heart. Myocardial hypertrophy and the progression to heart failure are highly heterogeneous and are the result of a combination of environmental and genetic factors. The genetic factors in particular have been recalcitrant to identification.
Mice with cardiac-specific over-expression of the calsequestrin (CSQ) gene develop a severe form of hypertrophic cardiomyopathy that serves as an appropriate mouse model of heart failure. Intriguingly, the extent of cardiomyopathy and the progression to heart failure are highly strain dependent, suggesting the existence of modifying genes in each strain. Using a backcross strategy and quantitative trait locus (QTL) mapping, we have identified three genetic loci that affect the progression of disease in this mouse model (Carlson, Suzuki, Marchuk and Rockman, in preparation). A gene on mouse chromosome 2 strongly affects the progression to heart failure, accounting for 37% of the phenotypic variation in the disease outcome. A locus on chromosome 4 shows a slightly lower effect on disease outcome. In addition, another locus on chromosome 3 strongly affects the extent of cardiomyopathy, as measured by % fractional shortening of the heart. We are in the process of refining the map positions of these three loci, with the goal of the identification of these genes affecting cardiomyopathy and heart failure in this mouse model. Polymorphic variants in these same genes in the human population may be the elusive genetic risk factors for heart failure. Once identified, these will be tested in case-control association studies with appropriate patient populations.
Advances in our understanding of fundamental biological events can often be made by the analysis of defects manifested in inherited diseases. The genes responsible for these genetic syndromes often encode proteins that act at critical points of the pathways that control fundamental biological processes such as cell division, differentiation, and cell death. This approach has lead to the discovery of novel gene products and/or biochemical pathways involved in disease, genes that in turn play a fundamental role in normal biological processes.
My laboratory has taken this genetic approach for the study of angiogenesis, beginning with Mendelian disorders of vascular dysplasia and progressing to more complex vascular phenotypes. Our objectives are twofold: (1) to gain specific knowledge of the pathology observed in these disorders, and (2) to provide basic knowledge on the role of these genes and gene products in angiogenesis. The first step is to identify the genetic loci that underlie these syndromes. These mapping and positional cloning endeavors become the basis for future molecular biological studies on the role of the mutant gene products in the pathology of the disease, and the role of the normal proteins in vascular development. In order to investigate disease mechanism and pathogenesis, we then create an appropriate transgenic or knockout mouse as an animal model of the disease. The animal model serves both as a tool to further understand the pathophysiology of the disease, and a more tractable system to begin to identify other factors (genetic and environmental) that may alter the phenotype. Coming full circle, we can determine if the factors identified in the animal model also modify the clinical phenotype in the human disease. We currently have four projects that utilize this approach, and a new initiative that begins with a mouse model of hypertrophic cardiomyopathy.
Project 1. Molecular Genetics of Arterio-Venous Communication: Hereditary Hemorrhagic Telangiectasia: Hereditary Hemorrhagic Telangiectasia (HHT or Osler-Weber-Rendu disease) is an autosomal dominant disorder characterized by hemorrhagic stroke, gastrointestinal bleeding, and other vascular pathology. The clinical features result from the development of focal vascular malformations characterized by direct arteriovenous shunts with a loss of the capillary beds. The pathology of this disorder suggests a critical role for the HHT gene(s) in vascular development and angiogenesis of the capillary bed. However, until our work on this disorder, the nature of the molecular defect remained unknown. We have shown that HHT is actually a group of related disorders with overlapping but distinct phenotypes and genetic etiologies (McAllister et al., 1994a; Porteous et al., 1994; Berg et al., 1996). We established genetic linkage at two distinct loci for HHT, one on chromosome 9q33 (McDonald et al., 1994) and the other on 12q13 (Johnson DW, et al., 1995). We subsequently identified the gene for HHT 1 as endoglin (McAllister et al., 1994b), a transforming growth factor-ÿ(TGF-ÿÿ) binding protein of endothelial cells, and the HHT 2 locus as the activin-like kinase receptor, ALK-1, which has sequence homology to type I TGF-ÿÿ receptors (Johnson et al., 1996). Expression analyses of the mutant allele for endoglin (McAllister et al., 1995; Gallione et al., 1998) and for ALK-1 (Berg et al., 1997; Klaus et al., 1998) has shown that most alleles lead to unstable message or reduced levels of protein, suggesting inherited haploinsufficiency. These data suggest a critical role for the TGF-ÿÿ signal transduction pathway in the pathology of this disease, and more significantly, in the development and/or repair of blood vessels.
Our research has more recently involved a combination of genetic and molecular biological approaches to further study the role of ALK-1 and endoglin in cardiovascular disease and angiogenesis. We are investigating whether sequence polymorphisms in the endoglin and/or ALK-1 genes are risk factors for cerebrovascular disease in the general population with retrospective case-control association studies. We have already shown that one sequence polymorphism in endoglin is associated with increased risk for hemorrhagic stroke (Alberts et al., 1997), an observation which has now been replicated by others in the Japanese population (Takenaka et al., 1999). We are currently attempting to understand how this intronic polymorphism may affect RNA splicing or message stability. Three endoglin coding-polymorphisms are also under investigation, as the intronic polymorphism may be in linkage disequilibrium with one of these.
Although both endoglin and ALK-1 share sequence homology to the TGF-ÿ family of receptors, little is known about their precise role in signaling. Due to the lack of a signaling assay for ALK-1, there is no evidence other than sequence homology that ALK-1 is a TGF-ÿ receptor. We created a signaling assay for ALK-1 by constructing a chimeric receptor consisting of the extracellular ligand-binding domain of ALK-1 fused to the kinase domain of the TGF-ÿ receptor TÿRI, which can activate a reporter gene driven by the PAI-1 promoter. Using this chimera, we have demonstrated ligand specific activation for TGF-ÿ1, -ÿÿ3 (but not -ÿÿ2), and an additional uncharacterized ligand present in serum (Lux et al., 1999). Significantly, this ligand specificity for the TGF-ÿ isoforms parallels that of endoglin. We have also shown that ALK-1 and endoglin can be immunoprecipitated together in a receptor complex (Lux et al., 1999), suggesting that HHT is a result of altered signaling via an endothelial-specific TGF-ÿ receptor complex.
We have used this signaling assay to attempt to identify the novel ligand present in serum. Results with all available mammalian TGF-ÿ family members were negative (Lux et al., 1999). The Drosophila SAX gene encodes a receptor which may be the most similar in this species to mammalian ALK-1. We have now shown that the Drosophila SAX ligand screw (SCW) activates the ALK-1 chimera in our assay (Lux, Arora, and Marchuk, unpublished). The reciprocal experiment, performed in the laboratory of our collaborator Kavita Arora (UC, Irvine) suggests that mammalian ALK-1 can partially substitute for SCW in Drosophila development. The combined data suggest that ALK-1 signaling may involve a novel TGF-ÿ related ligand, and that a novel biochemical pathway involved in fundamental angiogenic processes awaits identification. Attempts to clone the mammalian homologue of the SCW ligand are in progress, using a variety of bioinformatic, molecular and biochemical approaches. Using our signaling assay, we are attempting to identify the downstream effectors of this pathway, as well as characterize the changes in gene expression due to signaling through these receptors.
We also wish to create animal models for HHT1 and 2. We now have ALK-1 and endoglin knockout mice. Although in both cases the mutant homozygotes show embryonic lethality, we have recently identified gastrointestinal vascular malformations (telangiectasias) in the ALK-1 heterozygotes (Yu, McLendon, and Marchuk, unpublished). The mice have become a critical resource for future studies on HHT, as will be outlined in the section on Future Directions.
Project 2. Molecular Genetics of Venous Angiogenesis: Familial Venous Malformations: Venous malformations are composed of large vascular lumens lined by a single-layered flat mature endothelium, which are thus prone to hemorrhage. The cutaneous and visceral lesions occur as single or multiple lesions with a nodular or tumor-like appearance. The presence of a few families exhibiting autosomal dominant inheritance of these vascular lesions suggested that genetic linkage analysis and positional cloning could be used to identify the responsible gene(s). We confirmed an earlier report by the laboratories of Bjorn Olsen and Matt Warman of linkage to chromosome 9p21 for autosomal dominant venous malformations (Gallione et al., 1995). We subsequently mapped the gene for the tie-2 receptor kinase to the candidate interval, and in collaboration with this group, identified an identical mutation in the kinase domain of tie-2 for two large kindreds (Vikkula et al., 1996). In our laboratory, we subsequently identified a second missense mutations in tie-2 which causes FVM, and have shown that both known mutations constitutively activate the receptor (Calvert et al., 1999). Although the tie-2/angiopoietin pathway has been implicated in vasculogenesis and embryonic angiogenesis from knockout studies in the mouse, our work suggests that this pathway has a role in the maintenance of proper vascular structure extending into adulthood. We speculate that this pathway is involved in endothelial-smooth muscle association based on the anatomy of the vascular lesion.
We are now creating a transgenic mouse model of this disorder, by expressing both tie-2 mutations under the control of its own promoter. This mouse model will be most useful for our understanding of the initiating event in lesion formation in these families, since although the phenotype is expressed in the heterozygous state, there appears to be no global vascular pathology outside of the vascular lesions themselves.
We have also identified 5 additional families with a clinical presentation similar to our tie-2 venous malformation families, but which exclude the tie-2 locus by linkage analysis. In some families the lesions were classified as glomangiomas, a benign tumor derived from the glomus cells (smooth muscle derivative) of the vasculature. We have recently shown that these families map to chromosome 1p (Calvert et al. submitted), and are actively searching for mutations in genes mapping to the critical region.
Project 3. Molecular Genetics of Cerebrovascular Angiogenesis: Cerebral Cavernous Malformations: Cerebral cavernous malformations (CCM) are congenital vascular anomalies of the brain comprising focal, thin-walled, grossly dilated vascular spaces. The lesions are responsible for significant neurologic disability, in particular, intractable migraine, seizures, and hemorrhagic stroke. Autosomal dominant forms of CCM have been described and we and others have shown that a gene for CCM (CCM1) maps to chromosome 7q (Marchuk et al., 1995). Taking advantage of a shared disease haplotype in Mexican-American families, we were able to narrow the critical region to under 500 kb (Johnson et al., 1995c; and unpublished data). We have now identified the CCM1 gene as KRIT1, a recently discovered binding partner of the Krev-1/rap1a tumor suppressor gene (Sahoo et al., in press). A common mutation in most Hispanic families (16 of 21 families analyzed) confirms the founder effect in this population. Other Hispanic and non-Hispanic families harbor different mutations, all of which appear to be null alleles. These data show the strength of this genetic approach to cardiovascular disease, as the Krev-1/rap1a signaling pathway, although implicated in cancer (e.g. Tuberous sclerosis), has not previously been shown to be required for angiogenesis, nor has it been previously implicated in any cardiovascular pathology. We are currently working to create a mouse model of CCM1, as well as to characterize the role of this biochemical pathway in the pathology of hemorrhagic stroke associated with CCM. Mutation analysis is already underway to determine the involvement of KRIT1 mutations/polymorphisms in common (non-hereditary) cerebral cavernous malformations.
Project 4. Molecular Genetics of Capillary Angiogenesis: Hemangiomas: Our work on the autosomal dominant vascular disorders has identified genes involved in the regulation of vascular growth. However, all of these germline mutations are compatible with normal vascular development. We also wish to identify novel genes that might be essential for vasculogenesis and embryonic angiogenesis. Such genes can in principle be identified using human phenotypes, by searching for somatic mutations underlying non-inherited vascular anomalies. We are using this approach to identify the gene(s) underlying the most common tumor (of any kind) in infancy - hemangiomas.
Hemangiomas are benign tumors consisting primarily of proliferating capillaries, which often occur as an elevated purple or red spot on the skin. Hemangiomas usually develop shortly after birth, but are self-limiting and go through a characteristic two-staged process of growth and regression. The rapid proliferation stage suggests an uncontrolled stage of angiogenesis. Our hypothesis is that hemangiomas arise from an early somatic mutation within a critical gene for capillary angiogenesis. Due to the localized nature of the tumor, our prediction is that the mutated gene products will be acting in a cell-autonomous nature, with the tumor resulting from a clonal expansion cell containing the original mutation. Using a clonality assay based on non-random X-chromosome inactivation, we have shown that most proliferative hemangiomas appear mono-clonal (Walter and Marchuk, in preparation). We have also shown significant loss of heterozygosity for markers on chromosome 5q (Berg et al., in press), in the same region that we have identified a genetic susceptibility locus (see below). We are currently searching for mutations in the genes involved in the vascular endothelial growth factor (VEGF) pathway.
Although the great majority of hemangiomas occur sporadically, we have identified a number of families displaying autosomal dominant segregation of childhood hemangiomas (Blei et al., 1998). Using these families to identify genetic loci that may predispose children to hemangioma development, we have found linkage to a region on distal chromosome 5q (Walter et al., 1999). We hope that these independent lines of analysis will converge as we discover that some of these genetic loci are involved in both familial and sporadic cases, the mutations being inherited in the familial cases and acquired somatically in the sporadic cases.
Project 5. Molecular Genetics of Hypertrophic Cardiomyopathy: A Mouse Model of Heart Failure: Heart failure is a common cause of mortality in the United States. It is the final outcome of a variety of conditions, both primary and secondary, that affect the heart. Myocardial hypertrophy and the progression to heart failure are highly heterogeneous and are the result of a combination of environmental and genetic factors. The genetic factors in particular have been recalcitrant to identification.
Mice with cardiac-specific over-expression of the calsequestrin (CSQ) gene develop a severe form of hypertrophic cardiomyopathy that serves as an appropriate mouse model of heart failure. Intriguingly, the extent of cardiomyopathy and the progression to heart failure are highly strain dependent, suggesting the existence of modifying genes in each strain. Using a backcross strategy and quantitative trait locus (QTL) mapping, we have identified three genetic loci that affect the progression of disease in this mouse model (Carlson, Suzuki, Marchuk and Rockman, in preparation). A gene on mouse chromosome 2 strongly affects the progression to heart failure, accounting for 37% of the phenotypic variation in the disease outcome. A locus on chromosome 4 shows a slightly lower effect on disease outcome. In addition, another locus on chromosome 3 strongly affects the extent of cardiomyopathy, as measured by % fractional shortening of the heart. We are in the process of refining the map positions of these three loci, with the goal of the identification of these genes affecting cardiomyopathy and heart failure in this mouse model. Polymorphic variants in these same genes in the human population may be the elusive genetic risk factors for heart failure. Once identified, these will be tested in case-control association studies with appropriate patient populations.
Current Appointments & Affiliations
- Professor of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2005
- James B. Duke Distinguished Professor of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2014
- Director, Duke University Program in Genetics and Genomics, Molecular Genetics and Microbiology, Basic Science Departments 2009
- Director, Center for Experimental Genetics, Molecular Genetics and Microbiology, Basic Science Departments 2002
- Professor of Cell Biology, Cell Biology, Basic Science Departments 2022
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 1993
Contact Information
- 213 Research Dr, 265 Clinical and Research Labs, Durham, NC 27710
- Duke Box 3175, Durham, NC 27710
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douglas.marchuk@duke.edu
(919) 684-1945
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Marchuk Lab
- Background
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Education, Training, & Certifications
- Ph.D., The University of Chicago 1985
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Previous Appointments & Affiliations
- Vice Chair, Department of Molecular Genetics & Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2010 - 2016
- Associate Professor of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2000 - 2005
- Assistant Professor of Genetics, Molecular Genetics and Microbiology, Basic Science Departments 1993 - 2000
- Assistant Professor of Cell Biology, Cell Biology, Basic Science Departments 1994 - 1996
- Recognition
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Awards & Honors
- Research
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Selected Grants
- Medical Scientist Training Program awarded by National Institutes of Health 2022 - 2027
- Cell and Molecular Biology Training Program awarded by National Institutes of Health 2021 - 2026
- Genetic and Genomics Training Grant awarded by National Institutes of Health 2020 - 2025
- Signaling Aberrations and Cerebral Cavernous Malformation Pathogenesis awarded by National Institutes of Health 2015 - 2025
- A novel platform to determine RABEP2 function as a therapeutic target in human ischemic stroke awarded by American Heart Association 2022 - 2025
- ATTRACT: Arterial flow as attractor for endothelial cell migration - a new concept in vascular malformation and stroke regeneration awarded by Fondation Leducq 2018 - 2023
- Preparing Genetic Counselors for Genomic Medicine Research awarded by National Institutes of Health 2017 - 2023
- Brain Vasular Malformation Consortium: Predictors of clinical course awarded by The Regents of the University of California 2014 - 2023
- A consortium effort to translate therapies for neurological diseases via an immune-competent organotypic platform awarded by University of North Carolina - Chapel Hill 2021 - 2023
- Duke CTSA (TL1) Year 5 awarded by National Institutes of Health 2018 - 2023
- Multidisciplinary Heart and Vascular Diseases awarded by National Institutes of Health 1975 - 2023
- Identification of the precise developmental window and tissue bed for the somatic mutation causing Sturge Weber Syndrome awarded by Department of Defense 2021 - 2023
- Novel Targets for Stroke Intervention - Gene Discovery for Modulators of Infarction awarded by National Institutes of Health 2017 - 2022
- Pathogenesis of vascular malformations in hereditary hemorrhagic telangiectasia: from disease mechanism to new therapies awarded by Barrow Neurological Institute 2017 - 2022
- Medical Scientist Training Program awarded by National Institutes of Health 1997 - 2022
- Investigating the Role of Somatic Mutations in Arteriovenous Malformations awarded by National Institutes of Health 2020 - 2022
- Gene Replacement Therapy for a mouse model of Cerebral Cavernous Malformations awarded by StrideBio LLC 2021 - 2022
- Effect of Low Dose Oral Propranolol on Hemorrhage and Disease Progression in a Chronic Ccm3 Model of Cerebral Cavernous Malformations awarded by Be Brave for Life 2020 - 2021
- Endothelial Cell Lineage Studies in Cerebral Cavernous Malformations awarded by National Institutes of Health 2019 - 2021
- Characterizing lesion development in a mouse model of Sturge-Weber Syndrome awarded by Sturge-Weber Foundation 2020
- Genetics Training Grant awarded by National Institutes of Health 1979 - 2020
- Organization and Function of Cellular Structure awarded by National Institutes of Health 1975 - 2020
- to test whether propranolol will reduce lesion burden and/ or hemorrhage in a mouse model of Cerebral Cavernous malformations awarded by Barrow Neurological Institute 2018 - 2019
- Vascular malformation genesis vs. maintenance and progression: identifying the molecular pathways necessary for cerebral cavernous malformation (CCM) maintenance and progression through therapeutic studies with a novel CCM mouse phenotype awarded by American Heart Association 2018
- Development of BA-1049 for treatment of cerebral cavernous malformations awarded by BioAxone Biosciences, Inc. 2016 - 2018
- Functional Characterization of the GNAQ somatic mutation causing Sturge Weber syndrome awarded by National Institutes of Health 2015 - 2018
- Rock Inhibition as Therapy for Cerebral Cavernous Malformation awarded by University of Chicago 2016 - 2017
- Institutional Training Grant in Pediatric Cardiology awarded by National Institutes of Health 2009 - 2015
- Project 2: Innovative approaches to gauge progression of Sturge-Weber syndrome awarded by University of California - San Francisco 2009 - 2014
- Natural genetic variation regulating infarct volume awarded by National Institutes of Health 2009 - 2014
- Peripheral endothelial and muscle cell pathology in cardiovascular disease awarded by National Institutes of Health 2010 - 2013
- Studying Early-Stage Lesions in Mouse Models of Cerebral Cavernous Malformations awarded by National Institutes of Health 2011 - 2013
- Genesis and Progression of Cerebral Cavernous Malformations awarded by National Institutes of Health 2009 - 2013
- Genetic modifiers of dilated cardiomyopathy in adult Drosophila awarded by National Institutes of Health 2007 - 2012
- Identification of genetics modifiers of heart disease awarded by National Institutes of Health 2007 - 2011
- Genes That Regulate Progression of Kidney Disease and Its Cardiovascular Effects awarded by National Institutes of Health 2007 - 2009
- Investigation of the two-hit hypothesis for Cerebral Cavernous Malformations awarded by National Institutes of Health 2008 - 2009
- Duke PREP: Minority Recruitment into Biomedical Sciences awarded by National Institutes of Health 2003 - 2008
- Identification of Modifier Genes in Heart Disease awarded by National Institutes of Health 2005 - 2008
- Gene Discovery for Cerebral Cavernous Malformations awarded by National Institutes of Health 2002 - 2008
- Identifying the CCM3 Gene: Understanding Familial Stroke awarded by National Institutes of Health 2005 - 2007
- Modifier Genes in Heart Failure awarded by National Institutes of Health 2001 - 2007
- Mitochondrial DNA Stability and Mutagenesis awarded by Army Research Office 2004 - 2007
- Genes that Regulate Target Organ Damage in Hypertension awarded by National Institutes of Health 2001 - 2006
- Genetics of Hereditary Hemorrhagic Telangiectasia awarded by National Institutes of Health 1993 - 2006
- Investigating the function of the Mcgl Family awarded by Army Research Office 2001 - 2005
- Characterization of the role of Din7 in mitochondrial DNA replication and genome integrity in the yeast Saccharomyces cerevisiae awarded by Army Research Office 2002 - 2004
- A Mouse Model of Cerebral Cavernous Malformations awarded by National Institutes of Health 2000 - 2003
- The Genetics Of Hereditary Hemorrhagic Telangiectasia awarded by National Institutes of Health 1993 - 1999
- Diversity Of Tgf Beta Receptor Mutations In Hht Syndrome awarded by National Institutes of Health 1995 - 1998
- Cloning The Hereditary Hemorrhagic Telangiectasia Gene awarded by National Institutes of Health 1995 - 1996
- Cloning Of Hereditary Hemorrhagic Telangiectasia Gene awarded by National Institutes of Health 1994 - 1996
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External Relationships
- Angioma Alliance
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Reuter, Sean P., Mark H. Soonpaa, Dorothy Field, Ed Simpson, Michael Rubart-von der Lohe, Han Kyu Lee, Arthi Sridhar, et al. “Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.” Circulation 147, no. 2 (January 10, 2023): 142–53. https://doi.org/10.1161/CIRCULATIONAHA.122.061130.Full Text Link to Item
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Thompson, K. P., J. Sykes, P. Chandakkar, P. Marambaud, N. T. Vozoris, D. A. Marchuk, and M. E. Faughnan. “Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia.” Orphanet J Rare Dis 17, no. 1 (November 7, 2022): 405. https://doi.org/10.1186/s13023-022-02539-8.Full Text Link to Item
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Galeffi, F., D. A. Snellings, S. E. Wetzel-Strong, N. Kastelic, J. Bullock, C. J. Gallione, P. E. North, and D. A. Marchuk. “A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis.” Angiogenesis 25, no. 4 (November 2022): 493–502. https://doi.org/10.1007/s10456-022-09841-w.Full Text Link to Item
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Gallione, Carol J., Matthew R. Detter, Adrienne Sheline, Henrietta M. Christmas, Cornelia Lee, and Douglas A. Marchuk. “Genetic genealogy uncovers a founder deletion mutation in the cerebral cavernous malformations 2 gene.” Hum Genet 141, no. 11 (November 2022): 1761–69. https://doi.org/10.1007/s00439-022-02458-5.Full Text Link to Item
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Lee, Han Kyu, Do Hoon Kwon, David L. Aylor, and Douglas A. Marchuk. “A cross-species approach using an in vivo evaluation platform in mice demonstrates that sequence variation in human RABEP2 modulates ischemic stroke outcomes.” Am J Hum Genet 109, no. 10 (October 6, 2022): 1814–27. https://doi.org/10.1016/j.ajhg.2022.09.003.Full Text Open Access Copy Link to Item
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Romanos, Sharbel G., Abhinav Srinath, Ying Li, Bingqing Xie, Chang Chen, Yan Li, Thomas Moore, et al. “Circulating Plasma miRNA Homologs in Mice and Humans Reflect Familial Cerebral Cavernous Malformation Disease.” Transl Stroke Res, June 17, 2022. https://doi.org/10.1007/s12975-022-01050-3.Full Text Link to Item
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Hagan, Matthew J., Robert Shenkar, Abhinav Srinath, Sharbel G. Romanos, Agnieszka Stadnik, Mark L. Kahn, Douglas A. Marchuk, Romuald Girard, and Issam A. Awad. “Rapamycin in Cerebral Cavernous Malformations: What Doses to Test in Mice and Humans.” Acs Pharmacol Transl Sci 5, no. 5 (May 13, 2022): 266–77. https://doi.org/10.1021/acsptsci.2c00006.Full Text Link to Item
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Shenkar, Robert, Thomas Moore, Christian Benavides, Rhonda Lightle, Matthew R. Detter, Nicholas Hobson, Romuald Girard, et al. “Propranolol as therapy for cerebral cavernous malformations: a cautionary note.” J Transl Med 20, no. 1 (April 5, 2022): 160. https://doi.org/10.1186/s12967-022-03360-4.Full Text Link to Item
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Snellings, Daniel A., Romuald Girard, Rhonda Lightle, Abhinav Srinath, Sharbel Romanos, Ying Li, Chang Chen, et al. “Developmental venous anomalies are a genetic primer for cerebral cavernous malformations.” Nat Cardiovasc Res 1 (March 2022): 246–52. https://doi.org/10.1038/s44161-022-00035-7.Full Text Link to Item
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Cardinell, Jillian L., Joel M. Ramjist, Chaoliang Chen, Weisong Shi, Nhu Q. Nguyen, Tiffany Yeretsian, Matthew Choi, et al. “Quantification metrics for telangiectasia using optical coherence tomography.” Sci Rep 12, no. 1 (February 2, 2022): 1805. https://doi.org/10.1038/s41598-022-05272-1.Full Text Link to Item
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Li, Wenqing, Robert Shenkar, Mathew R. Detter, Thomas Moore, Christian Benavides, Rhonda Lightle, Romuald Girard, et al. “Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models.” J Clin Invest 131, no. 19 (October 1, 2021). https://doi.org/10.1172/JCI154909.Full Text Link to Item
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Thompson, K. P., J. Nelson, H. Kim, S. M. Weinsheimer, D. A. Marchuk, M. T. Lawton, T. Krings, M. E. Faughnan, and M. E. Brain Vascular Malformation Consortium HHT Investigator Group. “Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia.” Orphanet J Rare Dis 16, no. 1 (September 19, 2021): 390. https://doi.org/10.1186/s13023-021-02012-y.Full Text Link to Item
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Wetzel-Strong, Sarah E., Shantel Weinsheimer, Jeffrey Nelson, Ludmila Pawlikowska, Dewi Clark, Mark D. Starr, Yingmiao Liu, et al. “Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations.” Orphanet J Rare Dis 16, no. 1 (September 3, 2021): 372. https://doi.org/10.1186/s13023-021-02009-7.Full Text Link to Item
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Keränen, Sara, Santeri Suutarinen, Rahul Mallick, Johanna P. Laakkonen, Diana Guo, Ludmila Pawlikowska, Behnam Rezai Jahromi, et al. “Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation.” Acta Neurochir (Wien) 163, no. 9 (September 2021): 2503–14. https://doi.org/10.1007/s00701-021-04895-z.Full Text Link to Item
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Snellings, Daniel A., Courtney C. Hong, Aileen A. Ren, Miguel A. Lopez-Ramirez, Romuald Girard, Abhinav Srinath, Douglas A. Marchuk, Mark H. Ginsberg, Issam A. Awad, and Mark L. Kahn. “Cerebral Cavernous Malformation: From Mechanism to Therapy.” Circ Res 129, no. 1 (June 25, 2021): 195–215. https://doi.org/10.1161/CIRCRESAHA.121.318174.Full Text Link to Item
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Ren, Aileen A., Daniel A. Snellings, Yourong S. Su, Courtney C. Hong, Marco Castro, Alan T. Tang, Matthew R. Detter, et al. “PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism.” Nature 594, no. 7862 (June 2021): 271–76. https://doi.org/10.1038/s41586-021-03562-8.Full Text Link to Item
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Smegal, Lindsay F., Alison J. Sebold, Adrienne M. Hammill, Csaba Juhász, Warren D. Lo, Daniel K. Miles, Angus A. Wilfong, et al. “Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome.” Pediatr Neurol 119 (June 2021): 3–10. https://doi.org/10.1016/j.pediatrneurol.2021.02.006.Full Text Link to Item
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Li, Wenqing, Robert Shenkar, Mathew R. Detter, Thomas Moore, Christian Benavides, Rhonda Lightle, Romuald Girard, et al. “Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models.” J Clin Invest 131, no. 3 (February 1, 2021). https://doi.org/10.1172/JCI144893.Full Text Link to Item
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Thompson, K. P., J. Nelson, H. Kim, L. Pawlikowska, D. A. Marchuk, M. T. Lawton, Marie E. Faughnan, and Marie E. Brain Vascular Malformation Consortium HHT Investigator Group. “Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.” Orphanet J Rare Dis 16, no. 1 (January 6, 2021): 12. https://doi.org/10.1186/s13023-020-01579-2.Full Text Link to Item
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Lee, Han Kyu, Sarah E. Wetzel-Strong, David L. Aylor, and Douglas A. Marchuk. “A Neuroprotective Locus Modulates Ischemic Stroke Infarction Independent of Collateral Vessel Anatomy.” Front Neurosci 15 (2021): 705160. https://doi.org/10.3389/fnins.2021.705160.Full Text Open Access Copy Link to Item
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Detter, Matthew R., Robert Shenkar, Christian R. Benavides, Catherine A. Neilson, Thomas Moore, Rhonda Lightle, Nicholas Hobson, et al. “Novel Murine Models of Cerebral Cavernous Malformations.” Angiogenesis 23, no. 4 (November 2020): 651–66. https://doi.org/10.1007/s10456-020-09736-8.Full Text Link to Item
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Hong, Courtney C., Alan T. Tang, Matthew R. Detter, Jaesung P. Choi, Rui Wang, Xi Yang, Andrea A. Guerrero, et al. “Cerebral cavernous malformations are driven by ADAMTS5 proteolysis of versican.” J Exp Med 217, no. 10 (October 5, 2020). https://doi.org/10.1084/jem.20200140.Full Text Link to Item
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Kilian, Alexandra, Giuseppe A. Latino, Andrew J. White, Dewi Clark, Murali M. Chakinala, Felix Ratjen, Jamie McDonald, et al. “Genotype-Phenotype Correlations in Children with HHT.” J Clin Med 9, no. 9 (August 22, 2020). https://doi.org/10.3390/jcm9092714.Full Text Link to Item
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McKerracher, Lisa, Robert Shenkar, Matthew Abbinanti, Ying Cao, Amy Peiper, James K. Liao, Rhonda Lightle, et al. “A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease.” Transl Stroke Res 11, no. 3 (June 2020): 365–76. https://doi.org/10.1007/s12975-019-00725-8.Full Text Link to Item
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Harmon, Kelly A., Alyssa M. Day, Adrienne M. Hammill, Anna L. Pinto, Charles E. McCulloch, Anne M. Comi, and Anne M. National Institutes of Health Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. “Quality of Life in Children With Sturge-Weber Syndrome.” Pediatr Neurol 101 (December 2019): 26–32. https://doi.org/10.1016/j.pediatrneurol.2019.04.004.Full Text Link to Item
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Tang, Alan T., Katie R. Sullivan, Courtney C. Hong, Lauren M. Goddard, Aparna Mahadevan, Aileen Ren, Heidy Pardo, et al. “Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation.” Sci Transl Med 11, no. 520 (November 27, 2019). https://doi.org/10.1126/scitranslmed.aaw3521.Full Text Link to Item
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Snellings, Daniel A., Carol J. Gallione, Dewi S. Clark, Nicholas T. Vozoris, Marie E. Faughnan, and Douglas A. Marchuk. “Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Bi-allelic Loss of ENG or ACVRL1.” Am J Hum Genet 105, no. 5 (November 7, 2019): 894–906. https://doi.org/10.1016/j.ajhg.2019.09.010.Full Text Link to Item
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Lee, Han Kyu, Samuel J. Widmayer, Min-Nung Huang, David L. Aylor, and Douglas A. Marchuk. “Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains.” Genetics 213, no. 3 (November 2019): 1079–92. https://doi.org/10.1534/genetics.119.302555.Full Text Open Access Copy Link to Item
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Koskimäki, Janne, Dongdong Zhang, Yan Li, Laleh Saadat, Thomas Moore, Rhonda Lightle, Sean P. Polster, et al. “Transcriptome clarifies mechanisms of lesion genesis versus progression in models of Ccm3 cerebral cavernous malformations.” Acta Neuropathol Commun 7, no. 1 (August 19, 2019): 132. https://doi.org/10.1186/s40478-019-0789-0.Full Text Link to Item
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Georgieva, Petya B., Douglas A. Marchuk, Holger Gerhardt, and Holger Leducq ATTRACT Consortium*. “ATTRACT.” Circ Res 125, no. 3 (July 19, 2019): 262–64. https://doi.org/10.1161/CIRCRESAHA.119.315198.Full Text Link to Item
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Day, Alyssa M., Charles E. McCulloch, Adrienne M. Hammill, Csaba Juhász, Warren D. Lo, Anna L. Pinto, Daniel K. Miles, et al. “Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome.” Pediatr Neurol 96 (July 2019): 30–36. https://doi.org/10.1016/j.pediatrneurol.2018.12.002.Full Text Link to Item
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Lyne, Seán B., Romuald Girard, Janne Koskimäki, Hussein A. Zeineddine, Dongdong Zhang, Ying Cao, Yan Li, et al. “Biomarkers of cavernous angioma with symptomatic hemorrhage.” Jci Insight 4, no. 12 (June 20, 2019). https://doi.org/10.1172/jci.insight.128577.Full Text Link to Item
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Shenkar, Robert, Amy Peiper, Heidy Pardo, Thomas Moore, Rhonda Lightle, Romuald Girard, Nicholas Hobson, et al. “Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease.” Stroke 50, no. 3 (March 2019): 738–44. https://doi.org/10.1161/STROKEAHA.118.024058.Full Text Link to Item
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Zeineddine, Hussein A., Romuald Girard, Laleh Saadat, Le Shen, Rhonda Lightle, Thomas Moore, Ying Cao, et al. “Phenotypic characterization of murine models of cerebral cavernous malformations.” Lab Invest 99, no. 3 (March 2019): 319–30. https://doi.org/10.1038/s41374-018-0030-y.Full Text Link to Item
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Koskimäki, Janne, Romuald Girard, Yan Li, Laleh Saadat, Hussein A. Zeineddine, Rhonda Lightle, Thomas Moore, et al. “Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes.” Jci Insight 4, no. 3 (February 7, 2019). https://doi.org/10.1172/jci.insight.126167.Full Text Link to Item
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Wellman, Rebecca J., Su Bin Cho, Pratibha Singh, Miriya Tune, Carlos A. Pardo, Anne M. Comi, and Anne M. BVMC Sturge–Weber syndrome Project Workgroup. “Gαq and hyper-phosphorylated ERK expression in Sturge-Weber syndrome leptomeningeal blood vessel endothelial cells.” Vasc Med 24, no. 1 (February 2019): 72–75. https://doi.org/10.1177/1358863X18786068.Full Text Link to Item
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Day, Alyssa M., Adrienne M. Hammill, Csaba Juhász, Anna L. Pinto, E Steve Roach, Charles E. McCulloch, Anne M. Comi, and Anne M. National Institutes of Health Sponsor: Rare Diseases Clinical Research Network (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. “Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset.” Pediatr Neurol 90 (January 2019): 8–12. https://doi.org/10.1016/j.pediatrneurol.2018.04.009.Full Text Link to Item
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Detter, Matthew R., Daniel A. Snellings, and Douglas A. Marchuk. “Cerebral Cavernous Malformations Develop Through Clonal Expansion of Mutant Endothelial Cells.” Circ Res 123, no. 10 (October 26, 2018): 1143–51. https://doi.org/10.1161/CIRCRESAHA.118.313970.Full Text Link to Item
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Lee, Han Kyu, Sehwon Koh, Donald C. Lo, and Douglas A. Marchuk. “Neuronal IL-4Rα modulates neuronal apoptosis and cell viability during the acute phases of cerebral ischemia.” Febs J 285, no. 15 (August 2018): 2785–98. https://doi.org/10.1111/febs.14498.Full Text Open Access Copy Link to Item
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Pawlikowska, Ludmila, Jeffrey Nelson, Diana E. Guo, Charles E. McCulloch, Michael T. Lawton, Helen Kim, Marie E. Faughnan, and Marie E. Brain Vascular Malformation Consortium HHT Investigator Group. “Association of common candidate variants with vascular malformations and intracranial hemorrhage in hereditary hemorrhagic telangiectasia.” Mol Genet Genomic Med 6, no. 3 (May 2018): 350–56. https://doi.org/10.1002/mgg3.377.Full Text Link to Item
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Offermann, Elizabeth A., Aditya Sreenivasan, M Robert DeJong, Doris D. M. Lin, Charles E. McCulloch, Melissa G. Chung, Anne M. Comi, et al. “Reliability and Clinical Correlation of Transcranial Doppler Ultrasound in Sturge-Weber Syndrome.” Pediatr Neurol 74 (September 2017): 15-23.e5. https://doi.org/10.1016/j.pediatrneurol.2017.04.026.Full Text Link to Item
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McClung, Joseph M., Timothy J. McCord, Terence E. Ryan, Cameron A. Schmidt, Tom D. Green, Kevin W. Southerland, Jessica L. Reinardy, et al. “BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.” Circulation 136, no. 3 (July 18, 2017): 281–96. https://doi.org/10.1161/CIRCULATIONAHA.116.024873.Full Text Link to Item
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Shenkar, Robert, Changbin Shi, Cecilia Austin, Thomas Moore, Rhonda Lightle, Ying Cao, Lingjiao Zhang, et al. “RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of Cerebral Cavernous Malformations.” Stroke 48, no. 1 (January 2017): 187–94. https://doi.org/10.1161/STROKEAHA.116.015013.Full Text Link to Item
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Wetzel-Strong, Sarah E., Matthew R. Detter, and Douglas A. Marchuk. “The pathobiology of vascular malformations: insights from human and model organism genetics.” J Pathol 241, no. 2 (January 2017): 281–93. https://doi.org/10.1002/path.4844.Full Text Link to Item
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Girard, Romuald, Hussein A. Zeineddine, Courtney Orsbon, Huan Tan, Thomas Moore, Nick Hobson, Robert Shenkar, et al. “Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease.” J Neurosci Methods 271 (September 15, 2016): 14–24. https://doi.org/10.1016/j.jneumeth.2016.06.021.Full Text Link to Item
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Lee, Han Kyu, Sehoon Keum, Huaxin Sheng, David S. Warner, Donald C. Lo, and Douglas A. Marchuk. “Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume.” J Clin Invest 126, no. 8 (August 1, 2016): 2827–38. https://doi.org/10.1172/JCI84491.Full Text Open Access Copy Link to Item
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Shi, Changbin, Robert Shenkar, Hussein A. Zeineddine, Romuald Girard, Maged D. Fam, Cecilia Austin, Thomas Moore, et al. “B-Cell Depletion Reduces the Maturation of Cerebral Cavernous Malformations in Murine Models.” J Neuroimmune Pharmacol 11, no. 2 (June 2016): 369–77. https://doi.org/10.1007/s11481-016-9670-0.Full Text Link to Item
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Comi, Anne M., Mustafa Sahin, Adrienne Hammill, Emma H. Kaplan, Csaba Juhász, Paula North, Karen L. Ball, et al. “Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research.” Pediatr Neurol 58 (May 2016): 12–24. https://doi.org/10.1016/j.pediatrneurol.2015.11.009.Full Text Link to Item
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Dokun, Ayotunde O., Lingdan Chen, Mitsuharu Okutsu, Charles R. Farber, Surovi Hazarika, W Schuyler Jones, Damian Craig, et al. “ADAM12: a genetic modifier of preclinical peripheral arterial disease.” Am J Physiol Heart Circ Physiol 309, no. 5 (September 2015): H790–803. https://doi.org/10.1152/ajpheart.00803.2014.Full Text Link to Item
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Shenkar, Robert, Changbin Shi, Tania Rebeiz, Rebecca A. Stockton, David A. McDonald, Abdul Ghani Mikati, Lingjiao Zhang, et al. “Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.” Genet Med 17, no. 3 (March 2015): 188–96. https://doi.org/10.1038/gim.2014.97.Full Text Link to Item
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McDonald, David A., Changbin Shi, Robert Shenkar, Carol J. Gallione, Amy L. Akers, Stephanie Li, Nicholas De Castro, et al. “Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis.” Hum Mol Genet 23, no. 16 (August 15, 2014): 4357–70. https://doi.org/10.1093/hmg/ddu153.Full Text Link to Item
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Shen, Fanxia, Vincent Degos, Pei-Lun Chu, Zhenying Han, Erick M. Westbroek, Eun-Jung Choi, Douglas Marchuk, et al. “Endoglin deficiency impairs stroke recovery.” Stroke 45, no. 7 (July 2014): 2101–6. https://doi.org/10.1161/STROKEAHA.114.005115.Full Text Link to Item
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Abraham, Dennis M., and Douglas A. Marchuk. “Inhibition of the cardiomyocyte-specific troponin I-interacting kinase limits oxidative stress, injury, and adverse remodeling due to ischemic heart disease.” Circ Res 114, no. 6 (March 14, 2014): 938–40. https://doi.org/10.1161/CIRCRESAHA.113.303238.Full Text Link to Item
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Poe, Jonathan C., Evgueni I. Kountikov, Jacquelyn M. Lykken, Abirami Natarajan, Douglas A. Marchuk, and Thomas F. Tedder. “EndoU is a novel regulator of AICD during peripheral B cell selection.” J Exp Med 211, no. 1 (January 13, 2014): 57–69. https://doi.org/10.1084/jem.20130648.Full Text Link to Item
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Comi, Anne M., Douglas A. Marchuk, and Jonathan Pevsner. “A needle in a haystack: Sturge-Weber syndrome gene discovery.” Pediatr Neurol 49, no. 6 (December 2013): 391–92. https://doi.org/10.1016/j.pediatrneurol.2013.07.009.Full Text Link to Item
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Chu, Pei-Lun, Sehoon Keum, and Douglas A. Marchuk. “A novel genetic locus modulates infarct volume independently of the extent of collateral circulation.” Physiol Genomics 45, no. 17 (September 3, 2013): 751–63. https://doi.org/10.1152/physiolgenomics.00063.2013.Full Text Link to Item
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Guttmacher, A. E., D. A. Marchuk, S. O. Trerotola, and R. E. Pyeritz. “Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome),” August 29, 2013, 1–18. https://doi.org/10.1016/B978-0-12-383834-6.00055-0.Full Text
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Shirley, Matthew D., Hao Tang, Carol J. Gallione, Joseph D. Baugher, Laurence P. Frelin, Bernard Cohen, Paula E. North, Douglas A. Marchuk, Anne M. Comi, and Jonathan Pevsner. “Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ.” N Engl J Med 368, no. 21 (May 23, 2013): 1971–79. https://doi.org/10.1056/NEJMoa1213507.Full Text Link to Item
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Akers, Amy L., Karen L. Ball, Marianne Clancy, Anne M. Comi, Marie E. Faughnan, Rashmi Gopal-Srivastava, Thomas P. Jacobs, et al. “Brain Vascular Malformation Consortium: Overview, Progress and Future Directions.” J Rare Disord 1, no. 1 (April 1, 2013): 5.Link to Item
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Keum, Sehoon, Han Kyu Lee, Pei-Lun Chu, Matthew J. Kan, Min-Nung Huang, Carol J. Gallione, Michael D. Gunn, Donald C. Lo, and Douglas A. Marchuk. “Natural genetic variation of integrin alpha L (Itgal) modulates ischemic brain injury in stroke.” Plos Genet 9, no. 10 (2013): e1003807. https://doi.org/10.1371/journal.pgen.1003807.Full Text Open Access Copy Link to Item
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Tang, Hao, Kunhong Xiao, Lan Mao, Howard A. Rockman, and Douglas A. Marchuk. “Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunction.” J Mol Cell Cardiol 54 (January 2013): 101–11. https://doi.org/10.1016/j.yjmcc.2012.10.004.Full Text Link to Item
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McClung, Joseph M., Timothy J. McCord, Sehoon Keum, Soraya Johnson, Brian H. Annex, Douglas A. Marchuk, and Christopher D. Kontos. “Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice.” Am J Pathol 180, no. 5 (May 2012): 2156–69. https://doi.org/10.1016/j.ajpath.2012.01.032.Full Text Link to Item
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Lo, Warren, Douglas A. Marchuk, Karen L. Ball, Csaba Juhász, Lori C. Jordan, Joshua B. Ewen, Anne Comi, and Anne Brain Vascular Malformation Consortium National Sturge-Weber Syndrome Workgroup. “Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement.” Dev Med Child Neurol 54, no. 3 (March 2012): 214–23. https://doi.org/10.1111/j.1469-8749.2011.04169.x.Full Text Link to Item
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McDonald, David A., Changbin Shi, Robert Shenkar, Rebecca A. Stockton, Feifei Liu, Mark H. Ginsberg, Douglas A. Marchuk, and Issam A. Awad. “Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease.” Stroke 43, no. 2 (February 2012): 571–74. https://doi.org/10.1161/STROKEAHA.111.625467.Full Text Link to Item
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Lodder, Elisabeth M., Brendon P. Scicluna, Annalisa Milano, Albert Y. Sun, Hao Tang, Carol Ann Remme, Perry D. Moerland, et al. “Dissection of a quantitative trait locus for PR interval duration identifies Tnni3k as a novel modulator of cardiac conduction.” Plos Genet 8, no. 12 (2012): e1003113. https://doi.org/10.1371/journal.pgen.1003113.Full Text Link to Item
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Gallione, Carol J., Ann Solatycki, Issam A. Awad, James L. Weber, and Douglas A. Marchuk. “A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations.” Genet Med 13, no. 7 (July 2011): 662–66. https://doi.org/10.1097/GIM.0b013e318211ff8b.Full Text Link to Item
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McDonald, David A., Robert Shenkar, Changbin Shi, Rebecca A. Stockton, Amy L. Akers, Melanie H. Kucherlapati, Raju Kucherlapati, et al. “A novel mouse model of cerebral cavernous malformations based on the two-hit mutation hypothesis recapitulates the human disease.” Hum Mol Genet 20, no. 2 (January 15, 2011): 211–22. https://doi.org/10.1093/hmg/ddq433.Full Text Link to Item
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Ahn, Sun-Hee, Hitesh Deshmukh, Nicole Johnson, Lindsay G. Cowell, Thomas H. Rude, William K. Scott, Charlotte L. Nelson, et al. “Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.” Plos Pathog 6, no. 9 (September 2, 2010): e1001088. https://doi.org/10.1371/journal.ppat.1001088.Full Text Open Access Copy Link to Item
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Du, Fang, Emily F. Ozdowski, Ingrid K. Kotowski, Douglas A. Marchuk, and Nina Tang Sherwood. “Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia.” Hum Mol Genet 19, no. 10 (May 15, 2010): 1883–96. https://doi.org/10.1093/hmg/ddq064.Full Text Link to Item
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Gallione, Carol, Arthur S. Aylsworth, Jill Beis, Terri Berk, Barbara Bernhardt, Robin D. Clark, Carol Clericuzio, et al. “Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.” Am J Med Genet A 152A, no. 2 (February 2010): 333–39. https://doi.org/10.1002/ajmg.a.33206.Full Text Link to Item
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Keum, Sehoon, and Douglas A. Marchuk. “A locus mapping to mouse chromosome 7 determines infarct volume in a mouse model of ischemic stroke.” Circ Cardiovasc Genet 2, no. 6 (December 2009): 591–98. https://doi.org/10.1161/CIRCGENETICS.109.883231.Full Text Link to Item
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Wheeler, Ferrin C., Hao Tang, Odessa A. Marks, Tracy N. Hadnott, Pei-Lun Chu, Lan Mao, Howard A. Rockman, and Douglas A. Marchuk. “Tnni3k modifies disease progression in murine models of cardiomyopathy.” Plos Genet 5, no. 9 (September 2009): e1000647. https://doi.org/10.1371/journal.pgen.1000647.Full Text Link to Item
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Fernandez, Liliana, Douglas A. Marchuk, Jennifer L. Moran, David R. Beier, and Howard A. Rockman. “An N-ethyl-N-nitrosourea mutagenesis recessive screen identifies two candidate regions for murine cardiomyopathy that map to chromosomes 1 and 15.” Mamm Genome 20, no. 5 (May 2009): 296–304. https://doi.org/10.1007/s00335-009-9184-7.Full Text Link to Item
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Whitehead, K. J., A. C. Chan, S. Navankasattusas, W. Koh, N. R. London, J. Ling, A. H. Mayo, et al. “Erratum: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases (Nature Medicine (2009) 15 (177-184)).” Nature Medicine 15, no. 4 (April 1, 2009): 462. https://doi.org/10.1038/nm0409-462c.Full Text
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Akers, Amy L., Eric Johnson, Gary K. Steinberg, Joseph M. Zabramski, and Douglas A. Marchuk. “Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.” Hum Mol Genet 18, no. 5 (March 1, 2009): 919–30. https://doi.org/10.1093/hmg/ddn430.Full Text Link to Item
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Whitehead, Kevin J., Aubrey C. Chan, Sutip Navankasattusas, Wonshill Koh, Nyall R. London, Jing Ling, Anne H. Mayo, et al. “The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases.” Nat Med 15, no. 2 (February 2009): 177–84. https://doi.org/10.1038/nm.1911.Full Text Link to Item
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Hao, Qi, Hua Su, Douglas A. Marchuk, Radoslaw Rola, Yongqiang Wang, Weizhong Liu, William L. Young, and Guo-Yuan Yang. “Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation.” Am J Physiol Heart Circ Physiol 295, no. 6 (December 2008): H2250–56. https://doi.org/10.1152/ajpheart.00083.2008.Full Text Link to Item
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Shenkar, Robert, Palamadai N. Venkatasubramanian, Alice M. Wyrwicz, Jin-cheng Zhao, Changbin Shi, Amy Akers, Douglas A. Marchuk, and Issam A. Awad. “Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models.” Neurosurgery 63, no. 4 (October 2008): 790–97. https://doi.org/10.1227/01.NEU.0000315862.24920.49.Full Text Link to Item
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Gianfrancesco, F., T. Esposito, S. Penco, V. Maglione, C. L. Liquori, M. C. Patrosso, O. Zuffardi, A. Ciccodicola, D. A. Marchuk, and F. Squitieri. “ZPLD1 gene is disrupted in a patient with balanced translocation that exhibits cerebral cavernous malformations.” Neuroscience 155, no. 2 (August 13, 2008): 345–49. https://doi.org/10.1016/j.neuroscience.2008.05.030.Full Text Link to Item
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Dokun, Ayotunde O., Sehoon Keum, Surovi Hazarika, Yongjun Li, Gregory M. Lamonte, Ferrin Wheeler, Douglas A. Marchuk, and Brian H. Annex. “A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical hindlimb ischemia.” Circulation 117, no. 9 (March 4, 2008): 1207–15. https://doi.org/10.1161/CIRCULATIONAHA.107.736447.Full Text Link to Item
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Liquori, Christina L., Silvana Penco, Judith Gault, Tracey P. Leedom, Laura Tassi, Teresa Esposito, Issam A. Awad, et al. “Different spectra of genomic deletions within the CCM genes between Italian and American CCM patient cohorts.” Neurogenetics 9, no. 1 (February 2008): 25–31. https://doi.org/10.1007/s10048-007-0109-x.Full Text Link to Item
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Kim, H., D. A. Marchuk, L. Pawlikowska, Y. Chen, H. Su, G. Y. Yang, and W. L. Young. “Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations.” Acta Neurochir Suppl 105 (2008): 199–206. https://doi.org/10.1007/978-3-211-09469-3_38.Full Text Link to Item
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Williams, Redford B., Douglas A. Marchuk, Ilene C. Siegler, John C. Barefoot, Michael J. Helms, Beverly H. Brummett, Richard S. Surwit, et al. “Childhood socioeconomic status and serotonin transporter gene polymorphism enhance cardiovascular reactivity to mental stress.” Psychosom Med 70, no. 1 (January 2008): 32–39. https://doi.org/10.1097/PSY.0b013e31815f66c3.Full Text Link to Item
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Hale, Laura P., Dinushi Perera, Marcia R. Gottfried, Lillian Maggio-Price, Sudha Srinivasan, and Douglas Marchuk. “Neonatal co-infection with helicobacter species markedly accelerates the development of inflammation-associated colonic neoplasia in IL-10(-/-) mice.” Helicobacter 12, no. 6 (December 2007): 598–604. https://doi.org/10.1111/j.1523-5378.2007.00552.x.Full Text Link to Item
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Ostberg, A., G. Moreno, T. Su, N. Trisnowati, D. Marchuk, and D. Murrell. “Erratum: Genetic analysis of a family with hereditary glomuvenous malformations (Australasian Journal of Dermatology (2007) 48, (170-173)).” Australasian Journal of Dermatology 48, no. 4 (November 1, 2007): 261. https://doi.org/10.1111/j.1440-0960.2007.00407.x.Full Text
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Salzler, H. R., R. Griffiths, P. Ruiz, L. Chi, C. Frey, D. A. Marchuk, H. A. Rockman, and T. H. Le. “Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus.” Kidney Int 72, no. 10 (November 2007): 1226–32. https://doi.org/10.1038/sj.ki.5002519.Full Text Link to Item
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Ostberg, Anna, Gilberto Moreno, Tina Su, Niken Trisnowati, Douglas Marchuk, and Dédée F. Murrell. “Genetic analysis of a family with hereditary glomuvenous malformations.” Australas J Dermatol 48, no. 3 (August 2007): 170–73. https://doi.org/10.1111/j.1440-0960.2007.00373.x.Full Text Link to Item
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Gianfrancesco, Fernando, Milena Cannella, Tiziana Martino, Vittorio Maglione, Teresa Esposito, Gualtiero Innocenzi, Emilia Vitale, Christina L. Liquori, Douglas A. Marchuk, and Ferdinando Squitieri. “Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations.” Am J Med Genet B Neuropsychiatr Genet 144B, no. 5 (July 5, 2007): 691–95. https://doi.org/10.1002/ajmg.b.30381.Full Text Link to Item
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Young, William L., Pui-Yan Kwok, Ludmila Pawlikowska, Michael T. Lawton, Helen Kim, Pirro G. Hysi, and Douglas A. Marchuk. “Arteriovenous malformation.” J Neurosurg 106, no. 4 (April 2007): 731–32. https://doi.org/10.3171/jns.2007.106.4.731.Full Text Link to Item
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Donahue, M. P., D. A. Marchuk, and H. A. Rockman. “Reply.” Journal of the American College of Cardiology 49, no. 10 (March 13, 2007): 1106–7. https://doi.org/10.1016/j.jacc.2006.12.019.Full Text
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Liquori, Christina L., Michel J. Berg, Ferdinando Squitieri, Tracey P. Leedom, Louis Ptacek, Eric W. Johnson, and Douglas A. Marchuk. “Deletions in CCM2 are a common cause of cerebral cavernous malformations.” Am J Hum Genet 80, no. 1 (January 2007): 69–75. https://doi.org/10.1086/510439.Full Text Link to Item
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Pittman, Kristianna M., H Wolfgang Losken, Mark E. Kleinman, Jeffrey R. Marcus, Francine Blei, Geoffrey C. Gurtner, and Douglas A. Marchuk. “No evidence for maternal-fetal microchimerism in infantile hemangioma: a molecular genetic investigation.” J Invest Dermatol 126, no. 11 (November 2006): 2533–38. https://doi.org/10.1038/sj.jid.5700516.Full Text Link to Item
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Donahue, Mark P., Douglas A. Marchuk, and Howard A. Rockman. “Redefining heart failure: the utility of genomics.” J Am Coll Cardiol 48, no. 7 (October 3, 2006): 1289–98. https://doi.org/10.1016/j.jacc.2006.05.062.Full Text Link to Item
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Gallione, C. J., J. A. Richards, T. G. W. Letteboer, D. Rushlow, N. L. Prigoda, T. P. Leedom, A. Ganguly, et al. “SMAD4 mutations found in unselected HHT patients.” J Med Genet 43, no. 10 (October 2006): 793–97. https://doi.org/10.1136/jmg.2006.041517.Full Text Link to Item
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Carlson, Kerri M., Karen M. Yamaga, Kent A. Reinker, Yujen E. Hsia, Clyde Carpenter, Lucienne M. Abe, Andrea K. Perry, Donald A. Person, Douglas A. Marchuk, and Ellen M. Raney. “Precocious osteoarthritis in a family with recurrent COL2A1 mutation.” J Rheumatol 33, no. 6 (June 2006): 1133–36.Link to Item
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Pawlikowska, Ludmila, KY Trudy Poon, Achal S. Achrol, Charles E. McCulloch, Connie Ha, Kristen Lum, Jonathan G. Zaroff, et al. “Apolipoprotein Eɛ2 Is Associated with New Hemorrhage Risk in Brain Arteriovenous Malformations.” Neurosurgery 58, no. 5 (May 1, 2006): 838–43. https://doi.org/10.1227/01.NEU.0000209605.18358.E5.Full Text Link to Item
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Züchner, Stephan, Melanie E. Kail, Martha A. Nance, Perry C. Gaskell, Ingrid K. Svenson, Douglas A. Marchuk, Margaret A. Pericak-Vance, and Allison E. Ashley-Koch. “A new locus for dominant hereditary spastic paraplegia maps to chromosome 2p12.” Neurogenetics 7, no. 2 (May 2006): 127–29. https://doi.org/10.1007/s10048-006-0029-1.Full Text Link to Item
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Lux, Andreas, Fiona Salway, Holly K. Dressman, Gabriele Kröner-Lux, Mathias Hafner, Philip J. R. Day, Douglas A. Marchuk, and John Garland. “ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression.” Bmc Cardiovasc Disord 6 (April 4, 2006): 13. https://doi.org/10.1186/1471-2261-6-13.Full Text Link to Item
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Shianna, K. V., D. A. Marchuk, and M. K. Strand. “Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase.” Mitochondrion. 6, no. 2 (April 1, 2006): 94–101.
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Shianna, Kevin V., Douglas A. Marchuk, and Micheline K. Strand. “Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase.” Mitochondrion 6, no. 2 (April 2006): 94–101. https://doi.org/10.1016/j.mito.2006.02.003.Full Text Link to Item
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Plummer, Nicholas W., Teresa L. Squire, Sudha Srinivasan, Elizabeth Huang, Jon S. Zawistowski, Hiroaki Matsunami, Laura P. Hale, and Douglas A. Marchuk. “Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations.” Mamm Genome 17, no. 2 (February 2006): 119–28. https://doi.org/10.1007/s00335-005-0098-8.Full Text Link to Item
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Achrol, Achal S., Ludmila Pawlikowska, Charles E. McCulloch, KY Trudy Poon, Connie Ha, Jonathan G. Zaroff, S Claiborne Johnston, et al. “Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.” Stroke 37, no. 1 (January 2006): 231–34. https://doi.org/10.1161/01.STR.0000195133.98378.4b.Full Text Link to Item
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Liquori, Christina L., Michel J. Berg, Ferdinando Squitieri, Monica Ottenbacher, Marielle Sorlie, Tracey P. Leedom, Milena Cannella, et al. “Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus.” Hum Mutat 27, no. 1 (January 2006): 118. https://doi.org/10.1002/humu.9389.Full Text Link to Item
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Sweet, Kevin, Joseph Willis, Xiao-Ping Zhou, Carol Gallione, Takeshi Sawada, Pia Alhopuro, Sok Kean Khoo, et al. “Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.” Jama 294, no. 19 (November 16, 2005): 2465–73. https://doi.org/10.1001/jama.294.19.2465.Full Text Link to Item
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Pawlikowska, Ludmila, Mary N. Tran, Achal S. Achrol, Connie Ha, Esteban Burchard, Shweta Choudhry, Jonathan Zaroff, et al. “Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations.” Stroke 36, no. 10 (October 2005): 2278–80. https://doi.org/10.1161/01.STR.0000182253.91167.fa.Full Text Link to Item
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Zawistowski, Jon S., Lisa Stalheim, Mark T. Uhlik, Amy N. Abell, Brooke B. Ancrile, Gary L. Johnson, and Douglas A. Marchuk. “CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis.” Hum Mol Genet 14, no. 17 (September 1, 2005): 2521–31. https://doi.org/10.1093/hmg/ddi256.Full Text Link to Item
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Plummer, Nicholas W., Jon S. Zawistowski, and Douglas A. Marchuk. “Genetics of cerebral cavernous malformations.” Curr Neurol Neurosci Rep 5, no. 5 (September 2005): 391–96. https://doi.org/10.1007/s11910-005-0063-7.Full Text Link to Item
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Svenson, Ingrid K., Mark T. Kloos, Amy Jacon, Carol Gallione, April C. Horton, Margaret A. Pericak-Vance, Michael D. Ehlers, and Douglas A. Marchuk. “Subcellular localization of spastin: implications for the pathogenesis of hereditary spastic paraplegia.” Neurogenetics 6, no. 3 (September 2005): 135–41. https://doi.org/10.1007/s10048-005-0219-2.Full Text Link to Item
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Wheeler, Ferrin C., Liliana Fernandez, Kerri M. Carlson, Matthew J. Wolf, Howard A. Rockman, and Douglas A. Marchuk. “QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival.” Mamm Genome 16, no. 6 (June 2005): 414–23. https://doi.org/10.1007/s00335-005-2468-7.Full Text Link to Item
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Taylor, Warren D., David C. Steffens, Martha E. Payne, James R. MacFall, Douglas A. Marchuk, Ingrid K. Svenson, and K Ranga R. Krishnan. “Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression.” Arch Gen Psychiatry 62, no. 5 (May 2005): 537–44. https://doi.org/10.1001/archpsyc.62.5.537.Full Text Link to Item
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Lux, Andreas, Christian Beil, Meher Majety, Suzanne Barron, Carol J. Gallione, Hella-Monika Kuhn, Jonathan N. Berg, Petra Kioschis, Douglas A. Marchuk, and Mathias Hafner. “Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1.” J Biol Chem 280, no. 9 (March 4, 2005): 8482–93. https://doi.org/10.1074/jbc.M409197200.Full Text Link to Item
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Morris, Paul N., Benjamin J. Dunmore, Amir Tadros, Douglas A. Marchuk, Diane C. Darland, Patricia A. D’Amore, and Nicholas P. J. Brindle. “Functional analysis of a mutant form of the receptor tyrosine kinase Tie2 causing venous malformations.” J Mol Med (Berl) 83, no. 1 (January 2005): 58–63. https://doi.org/10.1007/s00109-004-0601-9.Full Text Link to Item
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Plummer, Nicholas W., Carol J. Gallione, Sudha Srinivasan, Jon S. Zawistowski, David N. Louis, and Douglas A. Marchuk. “Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations.” Am J Pathol 165, no. 5 (November 2004): 1509–18. https://doi.org/10.1016/S0002-9440(10)63409-8.Full Text Link to Item
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Pawlikowska, Ludmila, Mary N. Tran, Achal S. Achrol, Charles E. McCulloch, Connie Ha, Denise L. Lind, Tomoki Hashimoto, et al. “Polymorphisms in genes involved in inflammatory and angiogenic pathways and the risk of hemorrhagic presentation of brain arteriovenous malformations.” Stroke 35, no. 10 (October 2004): 2294–2300. https://doi.org/10.1161/01.STR.0000141932.44613.b1.Full Text Link to Item
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Lawton, Michael T., G Edward Vates, Alfredo Quinones-Hinojosa, William C. McDonald, Douglas A. Marchuk, and William L. Young. “Giant infiltrative cavernous malformation: clinical presentation, intervention, and genetic analysis: case report.” Neurosurgery 55, no. 4 (October 2004): 979–80. https://doi.org/10.1227/01.neu.0000137277.08281.48.Full Text Link to Item
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Svenson, Ingrid K., Mark T. Kloos, P Craig Gaskell, Martha A. Nance, James Y. Garbern, Shin-ichi Hisanaga, Margaret A. Pericak-Vance, Allison E. Ashley-Koch, and Douglas A. Marchuk. “Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations.” Neurogenetics 5, no. 3 (September 2004): 157–64. https://doi.org/10.1007/s10048-004-0186-z.Full Text Link to Item
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Verlaan, Dominique J., Sandra B. Laurent, Daniel L. Rochefort, Christina L. Liquori, Douglas A. Marchuk, Adrian M. Siegel, and Guy A. Rouleau. “CCM2 mutations account for 13% of cases in a large collection of kindreds with hereditary cavernous malformations.” Ann Neurol 55, no. 5 (May 2004): 757–58. https://doi.org/10.1002/ana.20112.Full Text Link to Item
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Gallione, Carol J., Gabriela M. Repetto, Eric Legius, Anil K. Rustgi, Susan L. Schelley, Sabine Tejpar, Grant Mitchell, Eric Drouin, Cornelius J. J. Westermann, and Douglas A. Marchuk. “A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4).” Lancet 363, no. 9412 (March 13, 2004): 852–59. https://doi.org/10.1016/S0140-6736(04)15732-2.Full Text Link to Item
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Whitehead, Kevin J., Nicholas W. Plummer, Jennifer A. Adams, Douglas A. Marchuk, and Dean Y. Li. “Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations.” Development 131, no. 6 (March 2004): 1437–48. https://doi.org/10.1242/dev.01036.Full Text Link to Item
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Abdalla, S. A., C. J. Gallione, R. J. Barst, E. M. Horn, J. A. Knowles, D. A. Marchuk, M. Letarte, and J. H. Morse. “Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia.” Eur Respir J 23, no. 3 (March 2004): 373–77. https://doi.org/10.1183/09031936.04.00085504.Full Text Link to Item
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Le, Thu H., Agnes B. Fogo, Harmony R. Salzler, Tania Vinogradova, Michael I. Oliverio, Douglas A. Marchuk, and Thomas M. Coffman. “Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency.” Hypertension 43, no. 2 (February 2004): 445–51. https://doi.org/10.1161/01.HYP.0000112423.28987.00.Full Text Link to Item
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Hashimoto, Tomoki, Michael T. Lawton, Gen Wen, Guo-Yuan Yang, Thomas Chaly, Campbell L. Stewart, Holly K. Dressman, Nicholas M. Barbaro, Douglas A. Marchuk, and William L. Young. “Gene microarray analysis of human brain arteriovenous malformations.” Neurosurgery 54, no. 2 (February 2004): 410–23. https://doi.org/10.1227/01.neu.0000103421.35266.71.Full Text Link to Item
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Xu, Bin, Yong Qin Wu, Madeleine Huey, Helen M. Arthur, Douglas A. Marchuk, Tomoki Hashimoto, William L. Young, and Guo-Yuan Yang. “Vascular endothelial growth factor induces abnormal microvasculature in the endoglin heterozygous mouse brain.” J Cereb Blood Flow Metab 24, no. 2 (February 2004): 237–44. https://doi.org/10.1097/01.WCB.0000107730.66603.51.Full Text Link to Item
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Le Corvoisier, Philippe, Hyun-Young Park, Kerri M. Carlson, Douglas A. Marchuk, and Howard A. Rockman. “Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy.” Hum Mol Genet 12, no. 23 (December 1, 2003): 3097–3107. https://doi.org/10.1093/hmg/ddg333.Full Text Link to Item
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Liquori, Christina L., Michel J. Berg, Adrian M. Siegel, Elizabeth Huang, Jon S. Zawistowski, T’Prien Stoffer, Dominique Verlaan, et al. “Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.” Am J Hum Genet 73, no. 6 (December 2003): 1459–64. https://doi.org/10.1086/380314.Full Text Link to Item
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Yip, A. G., A. Dürr, D. A. Marchuk, A. Ashley-Koch, A. Hentati, D. C. Rubinsztein, and E. Reid. “Meta-analysis of age at onset in spastin-associated hereditary spastic paraplegia provides no evidence for a correlation with mutational class.” J Med Genet 40, no. 9 (September 2003): e106. https://doi.org/10.1136/jmg.40.9.e106.Full Text Link to Item
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Berg, J., M. Porteous, D. Reinhardt, C. Gallione, S. Holloway, T. Umasunthar, A. Lux, W. McKinnon, D. Marchuk, and A. Guttmacher. “Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations.” J Med Genet 40, no. 8 (August 2003): 585–90. https://doi.org/10.1136/jmg.40.8.585.Full Text Link to Item
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Marchuk, Douglas A., Sudha Srinivasan, Teresa L. Squire, and Jon S. Zawistowski. “Vascular morphogenesis: tales of two syndromes.” Hum Mol Genet 12 Spec No 1 (April 1, 2003): R97-112. https://doi.org/10.1093/hmg/ddg103.Full Text Link to Item
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Brummett, Beverly H., Ilene C. Siegler, Douglas R. McQuoid, Ingrid K. Svenson, Douglas A. Marchuk, and David C. Steffens. “Associations among the NEO Personality Inventory, Revised and the serotonin transporter gene-linked polymorphic region in elders: effects of depression and gender.” Psychiatr Genet 13, no. 1 (March 2003): 13–18. https://doi.org/10.1097/00041444-200303000-00002.Full Text Link to Item
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Le Corvoisier, P., H. Y. Park, K. M. Carlson, M. P. Donahue, D. A. Marchuk, and H. A. Rockman. “Impact of genetic polymorphisms on heart failure prognosis.” Arch Mal Coeur Vaiss 96, no. 3 (March 2003): 197–206.Link to Item
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Srinivasan, Sudha, Martha A. Hanes, Tayeashai Dickens, Mary E. M. Porteous, S Paul Oh, Laura P. Hale, and Douglas A. Marchuk. “A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2.” Hum Mol Genet 12, no. 5 (March 1, 2003): 473–82. https://doi.org/10.1093/hmg/ddg050.Full Text Link to Item
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Williams, Redford B., Douglas A. Marchuk, Kishore M. Gadde, John C. Barefoot, Katherine Grichnik, Michael J. Helms, Cynthia M. Kuhn, et al. “Serotonin-related gene polymorphisms and central nervous system serotonin function.” Neuropsychopharmacology 28, no. 3 (March 2003): 533–41. https://doi.org/10.1038/sj.npp.1300054.Full Text Link to Item
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Reid, Evan, Mark Kloos, Allison Ashley-Koch, Lori Hughes, Simon Bevan, Ingrid K. Svenson, Felicia Lennon Graham, et al. “A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10).” Am J Hum Genet 71, no. 5 (November 2002): 1189–94. https://doi.org/10.1086/344210.Full Text Link to Item
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Suzuki, Miwako, Kerri M. Carlson, Douglas A. Marchuk, and Howard A. Rockman. “Genetic modifier loci affecting survival and cardiac function in murine dilated cardiomyopathy.” Circulation 105, no. 15 (April 16, 2002): 1824–29. https://doi.org/10.1161/01.cir.0000014926.32463.89.Full Text Link to Item
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Walter, Jeffrey W., Paula E. North, Milton Waner, Adam Mizeracki, Francine Blei, John W. T. Walker, John F. Reinisch, and Douglas A. Marchuk. “Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma.” Genes Chromosomes Cancer 33, no. 3 (March 2002): 295–303. https://doi.org/10.1002/gcc.10028.Full Text Link to Item
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Zawistowski, Jon S., Ilya G. Serebriiskii, Maximilian F. Lee, Erica A. Golemis, and Douglas A. Marchuk. “KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis.” Hum Mol Genet 11, no. 4 (February 15, 2002): 389–96. https://doi.org/10.1093/hmg/11.4.389.Full Text Link to Item
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Williams, R. B., D. A. Marchuk, K. M. Gadde, J. C. Barefoot, K. Grichnik, M. J. Helms, C. M. Kuhn, et al. “Psychosocial risk factors for CHD and biobehavioral mechanisms: The role of CNS serotonin and serotonin-related genes.” Psychosomatic Medicine 64, no. 1 (January 1, 2002): 86–87.Link to Item
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Steffens, David C., Ingrid Svenson, Douglas A. Marchuk, Robert M. Levy, Judith C. Hays, Elizabeth P. Flint, K Ranga Rama Krishnan, and Ilene C. Siegler. “Allelic differences in the serotonin transporter-linked polymorphic region in geriatric depression.” Am J Geriatr Psychiatry 10, no. 2 (2002): 185–91.Link to Item
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Svenson, I. K., A. E. Ashley-Koch, M. A. Pericak-Vance, and D. A. Marchuk. “A second leaky splice-site mutation in the spastin gene.” Am J Hum Genet 69, no. 6 (December 2001): 1407–9. https://doi.org/10.1086/324593.Full Text Link to Item
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Svenson, I. K., A. E. Ashley-Koch, P. C. Gaskell, T. J. Riney, W. J. Cumming, H. M. Kingston, E. L. Hogan, et al. “Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia.” Am J Hum Genet 68, no. 5 (May 2001): 1077–85. https://doi.org/10.1086/320111.Full Text Link to Item
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Berg, J. N., J. W. Walter, U. Thisanagayam, M. Evans, F. Blei, M. Waner, A. G. Diamond, D. A. Marchuk, and M. E. Porteous. “Evidence for loss of heterozygosity of 5q in sporadic haemangiomas: are somatic mutations involved in haemangioma formation?” J Clin Pathol 54, no. 3 (March 2001): 249–52. https://doi.org/10.1136/jcp.54.3.249.Full Text Link to Item
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Marchuk, D. A. “Pathogenesis of hemangioma.” J Clin Invest 107, no. 6 (March 2001): 665–66. https://doi.org/10.1172/JCI12470.Full Text Link to Item
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Ashley-Koch, A., E. R. Bonner, P. C. Gaskell, S. G. West, R. Tim, C. M. Wolpert, R. Jones, et al. “Fine mapping and genetic heterogeneity in the pure form of autosomal dominant familial spastic paraplegia.” Neurogenetics 3, no. 2 (March 2001): 91–97. https://doi.org/10.1007/s100480000098.Full Text Link to Item
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Calvert, J. T., S. Burns, T. J. Riney, T. Sahoo, S. J. Orlow, N. C. Nevin, C. Haisley-Royster, et al. “Additional glomangioma families link to chromosome 1p: no evidence for genetic heterogeneity.” Hum Hered 51, no. 3 (2001): 180–82. https://doi.org/10.1159/000053340.Full Text Link to Item
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Sahoo, T., E. Goenaga-Diaz, I. G. Serebriiskii, J. W. Thomas, E. Kotova, J. G. Cuellar, J. M. Peloquin, et al. “Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene.” Genomics 71, no. 1 (January 1, 2001): 123–26. https://doi.org/10.1006/geno.2000.6426.Full Text Link to Item
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Williams, R. B., D. A. Marchuk, K. M. Gadde, J. C. Barefoot, K. Grichnik, M. J. Helms, C. M. Kuhn, et al. “Lower SES and increased illness risk: A role for gene-environment interactions?” Psychosomatic Medicine 63, no. 1 (January 1, 2001): 111–111.Link to Item
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Williams, R. B., D. A. Marchuk, K. M. Gadde, J. C. Barefoot, K. Grichnik, M. J. Helms, C. M. Kuhn, et al. “Central nervous system serotonin function and cardiovascular responses to stress.” Psychosom Med 63, no. 2 (2001): 300–305. https://doi.org/10.1097/00006842-200103000-00016.Full Text Link to Item
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Hashimoto, T., C. W. Emala, S. Joshi, R. Mesa-Tejada, C. M. Quick, L. Feng, A. Libow, D. A. Marchuk, and W. L. Young. “Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations.” Neurosurgery 47, no. 4 (October 2000): 910–18. https://doi.org/10.1097/00006123-200010000-00022.Full Text Link to Item
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Svenson, I. K., A. E. Ashley-Koch, P. C. Gaskell, T. J. Riney, C. Warner, C. D. Farrell, R. M. N. Boustany, et al. “Mutation analysis of the spastin gene in hereditary spastic paraplegia type 4 - evidence of aberrant transcript splicing caused by mutations in noncanonical splice site sequences.” American Journal of Human Genetics 67, no. 4 (October 1, 2000): 375–375.Link to Item
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McDonald, J. E., F. J. Miller, S. E. Hallam, L. Nelson, D. A. Marchuk, and K. J. Ward. “Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred.” Am J Med Genet 93, no. 4 (August 14, 2000): 320–27. https://doi.org/10.1002/1096-8628(20000814)93:4<320::aid-ajmg12>3.0.co;2-r.Full Text Link to Item
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Gallione, C. J., E. A. Scheessele, D. Reinhardt, A. J. Duits, J. N. Berg, C. J. Westermann, and D. A. Marchuk. “Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect.” Hum Genet 107, no. 1 (July 2000): 40–44. https://doi.org/10.1007/s004390000326.Full Text Link to Item
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Williams, R. B., J. C. Barefoot, G. Clary, K. M. Gadde, K. Grichnik, M. J. Helms, C. M. Kuhn, et al. “34. Serotonin transporter genotypes, CSF 5HIAA, and cardiovascular reactivity to stress.” Biological Psychiatry 47, no. 8 (April 2000): S10–S10. https://doi.org/10.1016/s0006-3223(00)00467-4.Full Text
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Lux, A., C. J. Gallione, and D. A. Marchuk. “Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms.” Hum Mol Genet 9, no. 5 (March 22, 2000): 745–55. https://doi.org/10.1093/hmg/9.5.745.Full Text Link to Item
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Williams, R. B., J. C. Barefoot, G. L. Clary, K. M. Gadde, K. Grichnik, M. J. Helms, C. M. Kuhn, et al. “Serotonin transporter promoter genotypes, CNS serotonin turnover, and cardiovascular reactivity to stress.” Psychosomatic Medicine 62, no. 1 (January 1, 2000): 101–101.Link to Item
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Arthur, H. M., J. Ure, A. J. Smith, G. Renforth, D. I. Wilson, E. Torsney, R. Charlton, et al. “Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development.” Dev Biol 217, no. 1 (January 1, 2000): 42–53. https://doi.org/10.1006/dbio.1999.9534.Full Text Link to Item
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Pece-Barbara, N., U. Cymerman, S. Vera, D. A. Marchuk, and M. Letarte. “Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1.” Hum Mol Genet 8, no. 12 (November 1999): 2171–81. https://doi.org/10.1093/hmg/8.12.2171.Full Text Link to Item
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Sahoo, T., E. W. Johnson, J. W. Thomas, P. M. Kuehl, T. L. Jones, C. G. Dokken, J. W. Touchman, et al. “Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1).” Hum Mol Genet 8, no. 12 (November 1999): 2325–33. https://doi.org/10.1093/hmg/8.12.2325.Full Text Link to Item
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Calvert, J. T., T. J. Riney, C. D. Kontos, E. H. Cha, V. G. Prieto, C. R. Shea, J. N. Berg, et al. “Allelic and locus heterogeneity in inherited venous malformations.” Hum Mol Genet 8, no. 7 (July 1999): 1279–89. https://doi.org/10.1093/hmg/8.7.1279.Full Text Link to Item
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Lux, A., L. Attisano, and D. A. Marchuk. “Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1.” J Biol Chem 274, no. 15 (April 9, 1999): 9984–92. https://doi.org/10.1074/jbc.274.15.9984.Full Text Link to Item
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Walter, J. W., F. Blei, J. L. Anderson, S. J. Orlow, M. C. Speer, and D. A. Marchuk. “Genetic mapping of a novel familial form of infantile hemangioma.” Am J Med Genet 82, no. 1 (January 1, 1999): 77–83. https://doi.org/10.1002/(sici)1096-8628(19990101)82:1<77::aid-ajmg15>3.0.co;2-a.Full Text Link to Item
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Ríus, C., J. D. Smith, N. Almendro, C. Langa, L. M. Botella, D. A. Marchuk, C. P. Vary, and C. Bernabéu. “Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1.” Blood 92, no. 12 (December 15, 1998): 4677–90.Link to Item
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Marchuk, D. A. “Genetic abnormalities in hereditary hemorrhagic telangiectasia.” Curr Opin Hematol 5, no. 5 (September 1998): 332–38. https://doi.org/10.1097/00062752-199809000-00005.Full Text Link to Item
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Blei, F., J. Walter, S. J. Orlow, and D. A. Marchuk. “Familial segregation of hemangiomas and vascular malformations as an autosomal dominant trait.” Arch Dermatol 134, no. 6 (June 1998): 718–22. https://doi.org/10.1001/archderm.134.6.718.Full Text Link to Item
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Marchuk, D. A., A. E. Guttmacher, J. A. Penner, and P. Ganguly. “Report on the workshop on Hereditary Hemorrhagic Telangiectasia, July 10-11, 1997.” Am J Med Genet 76, no. 3 (March 19, 1998): 269–73.Link to Item
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Damji, K. F., C. J. Gallione, R. R. Allingham, B. Slotterbeck, A. E. Guttmacher, K. A. Pasyk, J. M. Vance, M. A. Pericak-Vance, M. C. Speer, and D. A. Marchuk. “Quantitative DNA pooling to increase the efficiency of linkage analysis in autosomal dominant disease.” Hum Genet 102, no. 2 (February 1998): 207–12. https://doi.org/10.1007/s004390050679.Full Text Link to Item
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Blei, F., J. Walter, S. J. Orlow, and D. A. Marchuk. “Erratum: Familial segregation of hemangiomas and vascular malformations as an autosomal dominant trait (Archives of Dermatology (June 1998) 134 (718- 722)).” Archives of Dermatology 134, no. 11 (January 1, 1998): 1425.
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Gallione, C. J., D. J. Klaus, E. Y. Yeh, T. T. Stenzel, Y. Xue, K. B. Anthony, K. A. McAllister, et al. “Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.” Hum Mutat 11, no. 4 (1998): 286–94. https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<286::AID-HUMU6>3.0.CO;2-B.Full Text Link to Item
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Klaus, D. J., C. J. Gallione, K. Anthony, E. Y. Yeh, J. Yu, A. Lux, D. W. Johnson, and D. A. Marchuk. “Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online.” Hum Mutat 12, no. 2 (1998): 137. https://doi.org/10.1002/(SICI)1098-1004(1998)12:2<137::AID-HUMU16>3.0.CO;2-J.Full Text Link to Item
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Berg, J. N., C. J. Gallione, T. T. Stenzel, D. W. Johnson, W. P. Allen, C. E. Schwartz, C. E. Jackson, M. E. Porteous, and D. A. Marchuk. “The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2.” Am J Hum Genet 61, no. 1 (July 1997): 60–67. https://doi.org/10.1086/513903.Full Text Link to Item
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Marchuk, D. A. “The molecular genetics of hereditary hemorrhagic telangiectasia.” Chest 111, no. 6 Suppl (June 1997): 79S-82S. https://doi.org/10.1378/chest.111.6_supplement.79s.Full Text Link to Item
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Alberts, M. J., J. P. Davis, C. Graffagnino, C. McClenny, D. Delong, C. Granger, M. H. Herbstreith, K. Boteva, D. A. Marchuk, and A. D. Roses. “Endoglin gene polymorphism as a risk factor for sporadic intracerebral hemorrhage.” Ann Neurol 41, no. 5 (May 1997): 683–86. https://doi.org/10.1002/ana.410410519.Full Text Link to Item
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Alberts, M. J., J. P. Davis, C. Graffagnino, C. McClenny, D. Delong, M. H. Herbstreith, C. Granger, K. Boteva, D. A. Marchuk, and A. D. Roses. “Polymorphism in endoglin as a risk factor for intracerebral hemorrhage.” Stroke 28, no. 1 (January 1, 1997): 69–69.Link to Item
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Vikkula, M., L. M. Boon, K. L. Carraway, J. T. Calvert, A. J. Diamonti, B. Goumnerov, K. A. Pasyk, et al. “Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2.” Cell 87, no. 7 (December 27, 1996): 1181–90. https://doi.org/10.1016/s0092-8674(00)81814-0.Full Text Link to Item
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Johnson, D. W., J. N. Berg, M. A. Baldwin, C. J. Gallione, I. Marondel, S. J. Yoon, T. T. Stenzel, et al. “Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.” Nat Genet 13, no. 2 (June 1996): 189–95. https://doi.org/10.1038/ng0696-189.Full Text Link to Item
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McKeever, P. E., T. R. Dennis, A. C. Burgess, P. S. Meltzer, D. A. Marchuk, and J. M. Trent. “Chromosome breakpoint at 17q11.2 and insertion of DNA from three different chromosomes in a glioblastoma with exceptional glial fibrillary acidic protein expression.” Cancer Genet Cytogenet 87, no. 1 (March 1996): 41–47. https://doi.org/10.1016/0165-4608(95)00237-5.Full Text Link to Item
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Berg, J. N., A. E. Guttmacher, D. A. Marchuk, and M. E. Porteous. “Clinical heterogeneity in hereditary haemorrhagic telangiectasia: are pulmonary arteriovenous malformations more common in families linked to endoglin?” J Med Genet 33, no. 3 (March 1996): 256–57. https://doi.org/10.1136/jmg.33.3.256.Full Text Link to Item
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Guttmacher, A. E., D. A. Marchuk, and R. I. White. “Hereditary hemorrhagic telangiectasia - Reply.” New England Journal of Medicine 334, no. 5 (February 1, 1996): 331–32.Link to Item
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Shovlin, C. L., and J. M. Hughes. “Hereditary hemorrhagic telangiectasia.” N Engl J Med 334, no. 5 (February 1, 1996): 330–31.Link to Item
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Cummings, L. M., J. M. Trent, and D. A. Marchuk. “Identification and mapping of type 1 neurofibromatosis (NF1) homologous loci.” Cytogenet Cell Genet 73, no. 4 (1996): 334–40. https://doi.org/10.1159/000134370.Full Text Link to Item
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Thiel, G., K. Marczinek, R. Neumann, R. Witkowski, D. A. Marchuk, and P. Nurnberg. “Somatic mutations in the neurofibromatosis 1 gene in gliomas and primitive neuroectodermal tumours.” Anticancer Research 15, no. 6 B (December 1, 1995): 2495–99.
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Johnson, E. W., L. M. Iyer, S. S. Rich, H. T. Orr, A. Gil-Nagel, J. H. Kurth, J. M. Zabramski, et al. “Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM interval of chromosome 7q contained in a well-defined YAC contig.” Genome Res 5, no. 4 (November 1995): 368–80. https://doi.org/10.1101/gr.5.4.368.Full Text Link to Item
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Guttmacher, A. E., D. A. Marchuk, and R. I. White. “Hereditary hemorrhagic telangiectasia.” N Engl J Med 333, no. 14 (October 5, 1995): 918–24. https://doi.org/10.1056/NEJM199510053331407.Full Text Link to Item
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McAllister, K. A., M. A. Baldwin, A. K. Thukkani, C. J. Gallione, J. N. Berg, M. E. Porteous, A. E. Guttmacher, and D. A. Marchuk. “Six novel mutations in the endoglin gene in hereditary hemorrhagic telangiectasia type 1 suggest a dominant-negative effect of receptor function.” Hum Mol Genet 4, no. 10 (October 1995): 1983–85. https://doi.org/10.1093/hmg/4.10.1983.Full Text Link to Item
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“Report and abstracts of the 4th International Workshop on Chromosome 9. Williamsburg, Virginia, USA, April 23-25, 1995.” Ann Hum Genet 59, no. 4 (October 1995): 347–91.Link to Item
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Johnson, D. W., J. N. Berg, C. J. Gallione, K. A. McAllister, J. P. Warner, E. A. Helmbold, D. S. Markel, C. E. Jackson, M. E. Porteous, and D. A. Marchuk. “A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12.” Genome Res 5, no. 1 (August 1995): 21–28. https://doi.org/10.1101/gr.5.1.21.Full Text Link to Item
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Johnson, D. W., M. Qumsiyeh, M. Benkhalifa, and D. A. Marchuk. “Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively.” Genomics 28, no. 2 (July 20, 1995): 356–57. https://doi.org/10.1006/geno.1995.1157.Full Text Link to Item
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Marchuk, D. A., C. J. Gallione, L. A. Morrison, C. L. Clericuzio, B. L. Hart, B. E. Kosofsky, D. N. Louis, J. F. Gusella, L. E. Davis, and V. L. Prenger. “A locus for cerebral cavernous malformations maps to chromosome 7q in two families.” Genomics 28, no. 2 (July 20, 1995): 311–14. https://doi.org/10.1006/geno.1995.1147.Full Text Link to Item
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Gallione, C. J., K. A. Pasyk, L. M. Boon, F. Lennon, D. W. Johnson, E. A. Helmbold, D. S. Markel, M. Vikkula, J. B. Mulliken, and M. L. Warman. “A gene for familial venous malformations maps to chromosome 9p in a second large kindred.” J Med Genet 32, no. 3 (March 1995): 197–99. https://doi.org/10.1136/jmg.32.3.197.Full Text Link to Item
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Greenspan, D. S., H. Northrup, K. S. Au, K. A. McAllister, C. A. Francomano, R. J. Wenstrup, D. A. Marchuk, and D. J. Kwiatkowski. “COL5A1: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos Syndrome type II.” Genomics 25, no. 3 (February 10, 1995): 737–39. https://doi.org/10.1016/0888-7543(95)80021-d.Full Text Link to Item
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Thiel, G., K. Marczinek, R. Neumann, R. Witkowski, D. A. Marchuk, and P. Nurnberg. “Somatic mutations in the neurofibromatosis 1 gene in gliomas and primitive neuroectodermal tumours.” Anticancer Res 15, no. 6B (1995): 2495–99.Link to Item
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Porteous, M. E., A. Curtis, O. Williams, D. Marchuk, S. S. Bhattacharya, and J. Burn. “Genetic heterogeneity in hereditary haemorrhagic telangiectasia.” J Med Genet 31, no. 12 (December 1994): 925–26. https://doi.org/10.1136/jmg.31.12.925.Full Text Link to Item
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McAllister, K. A., F. Lennon, B. Bowles-Biesecker, W. C. McKinnon, E. A. Helmbold, D. S. Markel, C. E. Jackson, A. E. Guttmacher, M. A. Pericak-Vance, and D. A. Marchuk. “Genetic heterogeneity in hereditary haemorrhagic telangiectasia: possible correlation with clinical phenotype.” J Med Genet 31, no. 12 (December 1994): 927–32. https://doi.org/10.1136/jmg.31.12.927.Full Text Link to Item
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McAllister, K. A., K. M. Grogg, D. W. Johnson, C. J. Gallione, M. A. Baldwin, C. E. Jackson, E. A. Helmbold, D. S. Markel, W. C. McKinnon, and J. Murrell. “Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.” Nat Genet 8, no. 4 (December 1994): 345–51. https://doi.org/10.1038/ng1294-345.Full Text Link to Item
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McDonald, M. T., K. A. Papenberg, S. Ghosh, A. A. Glatfelter, B. B. Biesecker, E. A. Helmbold, D. S. Markel, A. Zolotor, W. C. McKinnon, and J. L. Vanderstoep. “A disease locus for hereditary haemorrhagic telangiectasia maps to chromosome 9q33-34.” Nat Genet 6, no. 2 (February 1994): 197–204. https://doi.org/10.1038/ng0294-197.Full Text Link to Item
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Reyniers, E., K. De Boulle, D. A. Marchuk, L. B. Andersen, F. S. Collins, and P. J. Willems. “An EcoRI RFLP in the 5' region of the human NF1 gene.” Hum Genet 92, no. 6 (December 1993): 631. https://doi.org/10.1007/BF00420953.Full Text Link to Item
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Andersen, L. B., S. A. Tarlé, D. A. Marchuk, E. Legius, and F. S. Collins. “A compound nucleotide repeat in the neurofibromatosis (NF1) gene.” Hum Mol Genet 2, no. 7 (July 1993): 1083. https://doi.org/10.1093/hmg/2.7.1083-a.Full Text Link to Item
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McDonald, M. T., K. A. Papenberg, A. A. Glatfelter, J. L. Vander-Stoep, and D. A. Marchuk. “Dinucleotide repeat polymorphism at the human erythropoietin receptor locus (EPOR) at 19p13.” Hum Mol Genet 2, no. 5 (May 1993): 619. https://doi.org/10.1093/hmg/2.5.619-a.Full Text Link to Item
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Gutmann, D. H., M. Boguski, D. Marchuk, M. Wigler, F. S. Collins, and R. Ballester. “Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis.” Oncogene 8, no. 3 (March 1993): 761–69.Link to Item
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Legius, E., D. A. Marchuk, F. S. Collins, and T. W. Glover. “Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis.” Nat Genet 3, no. 2 (February 1993): 122–26. https://doi.org/10.1038/ng0293-122.Full Text Link to Item
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Andersen, L. B., R. Ballester, D. A. Marchuk, E. Chang, D. H. Gutmann, A. M. Saulino, J. Camonis, M. Wigler, and F. S. Collins. “A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity.” Mol Cell Biol 13, no. 1 (January 1993): 487–95. https://doi.org/10.1128/mcb.13.1.487-495.1993.Full Text Link to Item
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Andersen, L. B., R. Ballester, D. A. Marchuk, E. Chang, D. H. Gutmann, A. M. Saulino, J. Camonis, M. Wigler, and F. S. Collins. “A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity.” Molecular and Cellular Biology 13, no. 1 (January 1993): 487–95. https://doi.org/10.1128/mcb.13.1.487-495.1993.Full Text
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Kayes, L. M., W. T. Schroeder, D. A. Marchuk, F. S. Collins, V. M. Riccardi, M. Duvic, and K. Stephens. “The gene for a novel epidermal antigen maps near the neurofibromatosis 1 gene.” Genomics 14, no. 2 (October 1992): 369–76. https://doi.org/10.1016/s0888-7543(05)80228-9.Full Text Link to Item
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Legius, E., D. A. Marchuk, B. K. Hall, L. B. Andersen, M. R. Wallace, F. S. Collins, and T. W. Glover. “NF1-related locus on chromosome 15.” Genomics 13, no. 4 (August 1992): 1316–18. https://doi.org/10.1016/0888-7543(92)90055-w.Full Text Link to Item
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Marchuk, D. A., R. Tavakkol, M. R. Wallace, B. H. Brownstein, P. Taillon-Miller, C. T. Fong, E. Legius, L. B. Andersen, T. W. Glover, and F. S. Collins. “A yeast artificial chromosome contig encompassing the type 1 neurofibromatosis gene.” Genomics 13, no. 3 (July 1992): 672–80. https://doi.org/10.1016/0888-7543(92)90140-n.Full Text Link to Item
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Martin-Gallardo, A., D. A. Marchuk, J. Gocayne, A. R. Kerlavage, W. R. McCombie, J. C. Venter, F. S. Collins, and M. R. Wallace. “Sequencing and analysis of genomic fragments from the NF1 locus.” Dna Seq 3, no. 4 (1992): 237–43. https://doi.org/10.3109/10425179209034023.Full Text Link to Item
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Marchuk, D. A., A. M. Saulino, R. Tavakkol, M. Swaroop, M. R. Wallace, L. B. Andersen, A. L. Mitchell, D. H. Gutmann, M. Boguski, and F. S. Collins. “cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product.” Genomics 11, no. 4 (December 1991): 931–40. https://doi.org/10.1016/0888-7543(91)90017-9.Full Text Link to Item
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Andersen, L. B., M. R. Wallace, D. A. Marchuk, R. Tavakkol, A. Mitchell, A. M. Saulino, and F. S. Collins. “A highly polymorphic cDNA probe in the NF1 gene.” Nucleic Acids Res 19, no. 13 (July 11, 1991): 3754. https://doi.org/10.1093/nar/19.13.3754.Full Text Link to Item
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Marchuk, D., M. Drumm, A. Saulino, and F. S. Collins. “Construction of T-vectors, a rapid and general system for direct cloning of unmodified PCR products.” Nucleic Acids Res 19, no. 5 (March 11, 1991): 1154. https://doi.org/10.1093/nar/19.5.1154.Full Text Link to Item
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Cawthon, R. M., L. B. Andersen, A. M. Buchberg, G. F. Xu, P. O’Connell, D. Viskochil, R. B. Weiss, M. R. Wallace, D. A. Marchuk, and M. Culver. “cDNA sequence and genomic structure of EV12B, a gene lying within an intron of the neurofibromatosis type 1 gene.” Genomics 9, no. 3 (March 1991): 446–60. https://doi.org/10.1016/0888-7543(91)90410-g.Full Text Link to Item
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Andersen, L. B., M. R. Wallace, D. A. Marchuk, R. M. Cawthon, H. M. Odeh, R. Letcher, R. L. White, and F. S. Collins. “A polymorphic cDNA probe on chromosome 17q11.2 located within the NF1 gene [D17S376].” Nucleic Acids Res 19, no. 1 (January 11, 1991): 197. https://doi.org/10.1093/nar/19.1.197-a.Full Text Link to Item
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“Type 1 neurofibromatosis gene: correction.” Science 250, no. 4988 (December 21, 1990): 1749.Link to Item
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Upadhyaya, M., A. Cheryson, W. Broadhead, A. Fryer, D. J. Shaw, S. Huson, M. R. Wallace, L. B. Andersen, D. A. Marchuk, and D. Viskochil. “A 90 kb DNA deletion associated with neurofibromatosis type 1.” J Med Genet 27, no. 12 (December 1990): 738–41. https://doi.org/10.1136/jmg.27.12.738.Full Text Link to Item
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Ballester, R., D. Marchuk, M. Boguski, A. Saulino, R. Letcher, M. Wigler, and F. Collins. “The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.” Cell 63, no. 4 (November 16, 1990): 851–59. https://doi.org/10.1016/0092-8674(90)90151-4.Full Text Link to Item
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Wallace, M. R., L. B. Andersen, J. W. Fountain, H. M. Odeh, D. Viskochil, D. A. Marchuk, P. O’Connell, R. White, and F. S. Collins. “A chromosome jump crosses a translocation breakpoint in the von Recklinghausen neurofibromatosis region.” Genes Chromosomes Cancer 2, no. 4 (November 1990): 271–77. https://doi.org/10.1002/gcc.2870020404.Full Text Link to Item
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Wallace, M. R., D. A. Marchuk, L. B. Andersen, R. Letcher, H. M. Odeh, A. M. Saulino, J. W. Fountain, A. Brereton, J. Nicholson, and A. L. Mitchell. “Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients.” Science 249, no. 4965 (July 13, 1990): 181–86. https://doi.org/10.1126/science.2134734.Full Text Link to Item
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Marchuk, D., and F. S. Collins. “pYAC-RC, a yeast artificial chromosome vector for cloning DNA cut with infrequently cutting restriction endonucleases.” Nucleic Acids Res 16, no. 15 (August 11, 1988): 7743. https://doi.org/10.1093/nar/16.15.7743.Full Text Link to Item
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Fuchs, E., A. L. Tyner, G. J. Giudice, D. Marchuk, A. RayChaudhury, and M. Rosenberg. “The human keratin genes and their differential expression.” Curr Top Dev Biol 22 (1987): 5–34. https://doi.org/10.1016/s0070-2153(08)60097-6.Full Text Link to Item
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RayChaudhury, A., D. Marchuk, M. Lindhurst, and E. Fuchs. “Three tightly linked genes encoding human type I keratins: conservation of sequence in the 5'-untranslated leader and 5'-upstream regions of coexpressed keratin genes.” Mol Cell Biol 6, no. 2 (February 1986): 539–48. https://doi.org/10.1128/mcb.6.2.539-548.1986.Full Text Link to Item
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Marchuk, D., S. McCrohon, and E. Fuchs. “Complete sequence of a gene encoding a human type I keratin: sequences homologous to enhancer elements in the regulatory region of the gene.” Proc Natl Acad Sci U S A 82, no. 6 (March 1985): 1609–13. https://doi.org/10.1073/pnas.82.6.1609.Full Text Link to Item
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Fuchs, E., I. Hanukoglu, D. Marchuk, M. P. Grace, and K. H. Kim. “The nature and significance of differential keratin gene expression.” Ann N Y Acad Sci 455 (1985): 436–50. https://doi.org/10.1111/j.1749-6632.1985.tb50427.x.Full Text Link to Item
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Marchuk, D., S. McCrohon, and E. Fuchs. “Remarkable conservation of structure among intermediate filament genes.” Cell 39, no. 3 Pt 2 (December 1984): 491–98. https://doi.org/10.1016/0092-8674(84)90456-2.Full Text Link to Item
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Kim, K. H., D. Marchuk, and E. Fuchs. “Expression of unusually large keratins during terminal differentiation: balance of type I and type II keratins is not disrupted.” J Cell Biol 99, no. 5 (November 1984): 1872–77. https://doi.org/10.1083/jcb.99.5.1872.Full Text Link to Item
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Fuchs, E., and D. Marchuk. “Type I and type II keratins have evolved from lower eukaryotes to form the epidermal intermediate filaments in mammalian skin.” Proc Natl Acad Sci U S A 80, no. 19 (October 1983): 5857–61. https://doi.org/10.1073/pnas.80.19.5857.Full Text Link to Item
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Book Sections
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Roman, B. L., D. A. Marchuk, S. O. Trerotola, and R. E. Pyeritz. “Hereditary hemorrhagic telangiectasia (osler-weber-rendu syndrome).” In Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics: Cardiovascular, Respiratory, and Gastrointestinal Disorders, 115–40, 2019. https://doi.org/10.1016/B978-0-12-812532-8.00003-3.Full Text
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Comi, A. M., D. A. Marchuk, and J. Pevsner. “Sturge-Weber Syndrome.” In Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease: Fifth Edition, 945–53, 2014. https://doi.org/10.1016/B978-0-12-410529-4.00081-4.Full Text
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Kim, H., D. A. Marchuk, L. Pawlikowska, Y. Chen, H. Su, G. Y. Yang, and W. L. Young. “Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations.” In Cerebral Hemorrhage, 199–206. Springer Vienna, n.d. https://doi.org/10.1007/978-3-211-09469-3_38.Full Text
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Conference Papers
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Faughnan, M. E., J. Nelson, H. Kim, L. Pawlikowska, D. A. Marchuk, and M. T. Lawton. “Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.” In Angiogenesis, 22:604–604. SPRINGER, 2019.Link to Item
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Pawlikowska, L., J. Nelson, C. E. McCulloch, M. T. Lawton, D. A. Marchuk, H. Kim, and M. E. Faughnan. “Common genetic variants associated with immune or inflammatory traits and disease severity phenotypes in hereditary hemorrhagic telangiectasia.” In Angiogenesis, 22:591–92. SPRINGER, 2019.Link to Item
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Snellings, D. A., C. J. Gallione, D. S. Clark, N. T. Vozoris, M. E. Faughnan, and D. A. Marchuk. “HHT telangiectases contain biallelic mutations in ENG/ACVRL1.” In Angiogenesis, 22:592–592. SPRINGER, 2019.Link to Item
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Wetzel-Strong, S. E., J. Nelson, L. Pawlikowska, D. Clark, H. Kim, M. E. Faughnan, and D. A. Marchuk. “Circulating biomarkers associated with HHT phenotypes.” In Angiogenesis, 22:604–604. SPRINGER, 2019.Link to Item
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Koskimaki, Janne, Romuald Girard, Yan Li, Hussein Zeineddine, Rhonda Lightle, Thomas Moore, Sean Lyne, et al. “Novel and Known Genes Elucidated in Cerebral Cavernous Malformation Through Comparative Transcriptomic Analysis of Multiple Model Species and Human Microdissected Lesional Endothelial Cells.” In Stroke, Vol. 50. LIPPINCOTT WILLIAMS & WILKINS, 2019.Link to Item
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Gallione, C., L. Pawlikowska, H. Kim, M. E. Faughnan, and D. A. Marchuk. “Functional studies of the ACVRL1 c. 314-35A > G polymorphism in HHT1.” In Angiogenesis, 21:149–149. SPRINGER, 2018.Link to Item
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Marchuk, D. A., C. J. Gallione, and E. T. Cirulli-Rodgers. “HHT mutation discovery in the era of whole exome/genome sequencing.” In Angiogenesis, 18:530–31. SPRINGER, 2015.Link to Item
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Dokun, Ayotunde O., Mitsuharu Okutsu, Damian Craig, Svati H. Shah, W Schuyler Jones, Douglas A. Marchuk, R John Lye, and Brian H. Annex. “ADAM12 Modifies Severity of Peripheral Arterial Disease; Evidence From Preclinical and Human Studies.” In Circulation, Vol. 128. LIPPINCOTT WILLIAMS & WILKINS, 2013.Link to Item
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Tang, Hao, Kunhong Xiao, Lan Mao, Howard A. Rockman, and Douglas A. Marchuk. “Overexpression of Cardiac Troponin I-Interacting Kinase, a Cardiac-Specific MAPKKK, Promotes Cardiac Dysfunction.” In Circulation Research, Vol. 111. LIPPINCOTT WILLIAMS & WILKINS, 2012.Link to Item
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Hysi, Pirro, Helen Kim, Ludmila Pawlikowska, Charles E. McCulloch, Jonathan G. Zaroff, Stephen Sidney, Esteban G. Burchard, et al. “Association of interleukin-1 beta (IL1B) gene and brain arteriovenous malformation in caucasians.” In Journal of Neurosurgery, 106:A944–A944. AMER ASSOC NEUROLOGICAL SURGEONS, 2007.Link to Item
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Hysi, Pirro, Helen Kim, Ludmila Pawlikowska, Charles E. McCulloch, Jonathan G. Zaroff, Stephen Sidney, Esteban G. Burchard, et al. “Association of interleukin-1 beta (IL1B) gene and brain arteriovenous malformation in Caucasians.” In Stroke, 38:456–456. LIPPINCOTT WILLIAMS & WILKINS, 2007.Link to Item
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Fernandez, Lillana, Douglas A. Marchuk, Jennifer Moran, David R. Beier, and Howard A. Rockman. “An N-ethyl-N-nitrosourea mutagenesis screen identifies the proximal end of chromosome 1 as a candidate region for murine cardiomyopathy.” In Circulation, 114:166–166. LIPPINCOTT WILLIAMS & WILKINS, 2006.Link to Item
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Achrol, A. S., L. Pawlikowska, C. E. McCulloch, K. Y. T. Poon, C. Ha, J. G. Zaroff, S. C. Johnston, et al. “TNF alpha-238G > a promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.” In Stroke, 37:638–39. LIPPINCOTT WILLIAMS & WILKINS, 2006.Link to Item
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Shenkar, R., P. N. Venkatasubramanian, J. C. Zhao, E. Kohlmeir, D. A. Marchuk, T. J. Meade, A. M. Wyrwicz, and I. A. Awad. “Advanced imaging techniques reveal detailed angioarchitecture in cerebral cavernous malformations.” In Stroke, 37:699–700. LIPPINCOTT WILLIAMS & WILKINS, 2006.Link to Item
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Kuhn, C. M., K. Gadde, S. M. Schanberg, D. A. Marchuk, I. C. Siegler, R. S. Surwit, and R. B. Williams. “Serotonin transporter polymorphism influences the prolactin response to tryptophan and stress.” In Neuropsychopharmacology, 30:S141–S141. NATURE PUBLISHING GROUP, 2005.Link to Item
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Pedersen, B. R., K. Carlson, M. P. Donahue, W. E. Kraus, L. E. Wagoner, G. Dorn, D. A. Marchuk, E. R. Hauser, and H. A. Rockman. “Evidence for collagen type XXIV as a modifier of survival after heart failure.” In Circulation, 112:U472–U472. LIPPINCOTT WILLIAMS & WILKINS, 2005.Link to Item
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Lux, A., C. Beil, M. Majety, S. Barron, C. J. Gallione, H. M. Kuhn, J. N. Berg, P. Kioschis, D. A. Marchuk, and M. Hafner. “Human retroviral gag- and gag-pol-like proteins interact with the TGF-b receptor ALK1.” In European Journal of Cell Biology, 84:26–26. URBAN & FISCHER VERLAG, 2005.Link to Item
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Carlson, K. M., B. Pedersen, M. P. Donahue, E. R. Hauser, W. E. Kraus, H. A. Rockman, and D. A. Marchuk. “An association between COL24A1 and ejection fraction in a human heart failure population: Evidence supporting COL24A1 as a modifier gene in human heart failure.” In Circulation, 110:720–720. LIPPINCOTT WILLIAMS & WILKINS, 2004.Link to Item
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Donahue, M. P., M. J. Wofe, J. L. Jennings, B. Pedersen, E. R. Hauser, D. A. Marchuk, and W. E. Kraus. “PPAR17 polymorphism is associated with reduced cardiac function identifying it as a modifier of heart failure.” In Circulation, 110:555–555. LIPPINCOTT WILLIAMS & WILKINS, 2004.Link to Item
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Fernandez, L., D. A. Marchuk, D. R. Beier, and H. A. Rockman. “An N-ethyl-N-nitrosourea mutagenesis screen to identify novel genes causing heart failure.” In Circulation, 110:45–45. LIPPINCOTT WILLIAMS & WILKINS, 2004.Link to Item
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Carlson, K. M., E. R. Hauser, M. P. Donahue, W. E. Kraus, H. A. Rockman, and D. A. Marchuk. “Identification of COL24A1 as a novel candidate gene for heart failure in mice and humans.” In American Journal of Human Genetics, 73:515–515. UNIV CHICAGO PRESS, 2003.Link to Item
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Gallione, C. J., G. M. Repetto, E. Legius, A. K. Rustgi, S. L. Schelley, M. Dunlop, G. Mitchell, E. Drouin, C. J. J. Westermann, and D. A. Marchuk. “Mutations in SMAD4 cause a combined Hereditary Hemorrhage Telangiectasia-juvenile Polyposis syndrome.” In American Journal of Human Genetics, 73:211–211. UNIV CHICAGO PRESS, 2003.Link to Item
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Kloos, M. T., E. Crocker, C. Haisley-Royster, C. L. Hunter, T. P. Leedom, N. C. Nevin, S. J. Orlow, et al. “Molecular analysis of the glomulin gene in glomuvenous malformation families.” In American Journal of Human Genetics, 73:571–571. UNIV CHICAGO PRESS, 2003.Link to Item
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Liquori, C. L., V. Maglione, F. Balogun, M. Cannella, E. Huang, L. Hughes, T. Leedom, F. Squitieri, and D. A. Marchuk. “Reduction in the minimal candidate region of cerebral cavernous malformations type 3 (CCM3) on chromosome 3q26.31-27.3.” In American Journal of Human Genetics, 73:491–491. UNIV CHICAGO PRESS, 2003.Link to Item
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Shianna, K. V., H. Hullinger, M. K. Strand, and D. A. Marchuk. “Functional analysis of yeast and human NADH kinase in Saccharomyces cerevisiae: implications for mitochondrial genome stability and neurodegenerative disease.” In American Journal of Human Genetics, 73:179–179. UNIV CHICAGO PRESS, 2003.Link to Item
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Squire, T. L., S. Srinivasan, R. J. Akhurst, H. M. Arthur, and D. A. Marchuk. “Investigation of TGF-beta plasma levels as a modifier of the phenotype of hereditary hemorrhagic telangiectasia.” In American Journal of Human Genetics, 73:574–574. UNIV CHICAGO PRESS, 2003.Link to Item
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Svenson, I. K., M. T. Kloos, P. C. Gaskell, M. A. Nance, J. Y. Garbern, M. A. Pericak-Vance, A. E. Ashley-Koch, and D. A. Marchuk. “An intragenic modifier of hereditary spastic paraplegia due to spastin gene mutation suggests a role for cyclin-dependent kinase 5 in HSP pathogenesis.” In American Journal of Human Genetics, 73:550–550. UNIV CHICAGO PRESS, 2003.Link to Item
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Zawistowski, J. S., N. W. Plummer, D. D. Chang, and D. A. Marchuk. “Astrocytic expression of the cerebral cavernous malformations type 1 gene, KRIT1, and its interaction partner ICAP1 suggests a role in formation or maintenance of the blood-brain barrier.” In American Journal of Human Genetics, 73:551–551. UNIV CHICAGO PRESS, 2003.Link to Item
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Zhang, L., M. T. Kloos, S. West, P. C. Gaskell, I. K. Svenson, M. A. Pericak-Vance, D. A. Marchuk, and A. E. Ashley-Koch. “A Genomic screen reveals evidence for novel SPG loci.” In American Journal of Human Genetics, 73:470–470. UNIV CHICAGO PRESS, 2003.Link to Item
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Carlson, K. M., E. R. Hauser, M. P. Donahue, W. E. Kraus, H. A. Rockman, and D. A. Marchuk. “Collagen XXIV, alpha 1: A novel candidate gene for the modification of heart failure outcome in both mice and humans.” In Circulation, 108:120–120. LIPPINCOTT WILLIAMS & WILKINS, 2003.Link to Item
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Le Corvoisier, P., K. M. Carlson, L. Mao, D. A. Marchuk, and H. A. Rockman. “Quantitative trait loci mapping identifies a novel modifier gene affecting heart function on distal mouse chromosome 2.” In Circulation, 106:139–40. LIPPINCOTT WILLIAMS & WILKINS, 2002.Link to Item
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Carlson, K. M., K. Reinker, D. Person, L. M. Abe, A. K. Perry, K. M. Yamaga, and D. A. Marchuk. “Identification of a Col2A1 mutation in a Micronesian family with autosomal dominant precocious osteoarthritis.” In American Journal of Human Genetics, 71:212–212. UNIV CHICAGO PRESS, 2002.Link to Item
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Kloos, M. T., E. Reid, A. Ashley-Koch, L. Hughes, S. Bevan, I. Svenson, P. C. Gaskell, et al. “A kinesin heavy chain (KIF5A) mutation in Hereditary Spastic Paraplegia (SPG10).” In American Journal of Human Genetics, 71:165–165. UNIV CHICAGO PRESS, 2002.Link to Item
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Plummer, N. W., M. W. Becher, and D. A. Marchuk. “A mouse model of cerebral cavernous malformations generated by targeted mutation of the mouse Ccm1 (Krit1) gene.” In American Journal of Human Genetics, 71:520–520. UNIV CHICAGO PRESS, 2002.Link to Item
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Srinivasan, S., T. Dickens, L. P. Hale, and D. A. Marchuk. “A murine model for hereditary hemorrhagic telangiectasia type 2.” In American Journal of Human Genetics, 71:542–542. UNIV CHICAGO PRESS, 2002.Link to Item
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Suzuki, M., K. M. Carlson, L. Mao, D. A. Marchuk, and H. A. Rockman. “A genetic modifier locus affecting survival maps to chromosome 2 using quantitative trait loci analysis in a murine model of dilated cardiomyopathy.” In Circulation, 104:127–127. LIPPINCOTT WILLIAMS & WILKINS, 2001.Link to Item
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Carlson, K. M., M. Suzuki, N. Golson, H. A. Rockman, and D. A. Marchuk. “Loci mapping to chromosomes 3 and 9 affect left ventricular dilatation and survival in a transgenic mouse model of dilated cardiomyopathy and heart failure.” In American Journal of Human Genetics, 69:538–538. UNIV CHICAGO PRESS, 2001.Link to Item
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Walter, J. W., P. E. North, A. Mizeracki, M. Waner, J. F. Reinisch, J. Walker, F. Blei, C. Patterson, and D. A. Marchuk. “Somatic mutations in sporadic juvenile hemangioma.” In American Journal of Human Genetics, 69:554–554. UNIV CHICAGO PRESS, 2001.Link to Item
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Zawistowski, J. S., I. G. Serebriiskii, M. F. Lee, E. A. Golemis, and D. A. Marchuk. “The CCM1 gene product KRIT1 interacts with the integrin binding protein ICAP-1.” In American Journal of Human Genetics, 69:636–636. UNIV CHICAGO PRESS, 2001.Link to Item
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Suzuki, M., A. Rapacciuolo, L. Mao, S. A. Thomas, and H. A. Rockman. “Lack of endogenous norepinephrine and epinephrine prevents mortality and the decline in cardiac function in a murine model of dilated cardiomyopathy.” In Circulation, 104:127–127, 2001.Link to Item
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Sahoo, T., I. Serebriiskil, E. Kotova, J. Peloquin, E. Golemis, E. W. Johnson, and D. A. Marchuk. “Identification of the authentic full length amino acid sequence of Krit1 (CCM1) utilizing a combination of computational gene-prediction tools and RT-PCR.” In American Journal of Human Genetics, 67:261–261. UNIV CHICAGO PRESS, 2000.Link to Item
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Walter, J. W., P. E. North, A. Mizeracki, M. Waner, and D. A. Marchuk. “Non-random X-inactivation suggests that juvenile hemangiomas are monoclonally derived.” In American Journal of Human Genetics, 67:75–75. UNIV CHICAGO PRESS, 2000.Link to Item
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Calvert, J. T., T. J. Riney, M. C. Speer, N. C. Nevin, S. A. Simpson, and D. A. Marchuk. “A second locus for inherited venous malformations maps to chromosome 1p.” In American Journal of Human Genetics, 65:A17–A17. UNIV CHICAGO PRESS, 1999.Link to Item
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Sahoo, T., J. W. Thomas, S. Q. Lee-Lin, P. M. Kuehl, C. Dokken, E. W. Johnson, E. D. Green, and D. A. Marchuk. “Physical and transcript map of CCM1 candidate interval on chromosome 7q.” In American Journal of Human Genetics, 65:A418–A418. UNIV CHICAGO PRESS, 1999.Link to Item
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Walter, J. W., J. N. Berg, M. Evans, D. Reinhardt, U. Thisanayagam, F. Blei, A. Diamond, M. Waner, D. A. Marchuk, and M. E. M. Porteous. “Loss of heterozygosity of 5q in sporadic hemangiomas suggests that somatic mutations are involved with hemangioma development.” In American Journal of Human Genetics, 65:A328–A328. UNIV CHICAGO PRESS, 1999.Link to Item
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Lux, A., L. Attisano, and D. A. Marchuk. “A search for the ALK-1 ligand and the role of endoglin: The two HHT genes.” In Naunyn Schmiedebergs Archives of Pharmacology, 358:R214–R214. SPRINGER VERLAG, 1998.Link to Item
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Stenzel, T. T., A. Lux, and D. A. Marchuk. “Detection of endoglin mutations in hereditary hemorrhagic telangiectasia (HHT) by western blot.” In American Journal of Pathology, 151:G22–G22. AMER SOC INVESTIGATIVE PATHOLOGY, INC, 1997.Link to Item
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Calvert, J. T., J. Berg, N. C. Nevin, S. A. Simpson, and D. A. Marchuk. “Genetic heterogeneity in familial venous malformations syndrome (FVM).” In American Journal of Human Genetics, 61:A270–A270. CELL PRESS, 1997.Link to Item
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Johnson, D. W., and D. A. Marchuk. “Identification of a new member of the myotonic dystrophy protein kinase gene family.” In American Journal of Human Genetics, 61:A381–A381. CELL PRESS, 1997.Link to Item
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Stenzel, T. T., C. J. Gallione, D. J. Klaus, E. Y. Yeh, A. Lux, Y. Xue, K. B. Anthony, et al. “Mutation and expression analysis of the endoglin gene in Hereditary Hemorrhagic Telangiectasia reveals null alleles: A new model for pathogenesis.” In American Journal of Human Genetics, 61:A348–A348. CELL PRESS, 1997.Link to Item
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Walter, J. W., F. M. Blei, and D. A. Marchuk. “Description of a novel hereditary form of capillary hemangioma and genetic mapping of predisposing chromosomal loci.” In American Journal of Human Genetics, 61:A299–A299. CELL PRESS, 1997.Link to Item
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JOHNSON, D. W., J. N. BERG, C. J. GALLIONE, K. A. MCALLISTER, J. P. WARNER, E. A. HELMBOLD, D. S. MARKEL, C. E. JACKSON, M. E. M. PORTEOUS, and D. A. MARCHUK. “A 2ND LOCUS FOR HEREDITARY HEMORRHAGIC TELANGIECTASIA MAPS TO CHROMOSOME-12.” In American Journal of Human Genetics, 57:1116–1116. UNIV CHICAGO PRESS, 1995.Link to Item
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JOHNSON, E. W., E. D. GREEN, S. S. RICH, H. T. ORR, A. GILNAGEL, J. H. KURTH, J. M. ZABRAMSKI, et al. “A GENE FOR FAMILIAL CEREBRAL CAVERNOUS MALFORMATION MAPS TO A 4-CM REGION OF CHROMOSOME 7Q IN SEVERAL FAMILIES.” In American Journal of Human Genetics, 57:1117–1117. UNIV CHICAGO PRESS, 1995.Link to Item
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MCALLISTER, K. A., M. A. BALWIN, A. K. THUKKANI, C. J. GALLIONE, J. M. BERG, M. E. PORTEOUS, A. E. GUTTMACHER, and D. A. MARCHUK. “6 ADDITIONAL MUTATIONS IN THE ENDOGLIN GENE IN HEREDITARY HEMORRHAGIC TELANGIECTASIA TYPE-1 SUGGEST A DOMINANT-NEGATIVE EFFECT OF RECEPTOR FUNCTION.” In American Journal of Human Genetics, 57:1269–1269. UNIV CHICAGO PRESS, 1995.Link to Item
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