Marilyn Jo Telen

Journal Article J Gerontol A Biol Sci Med Sci · May 7, 2026 BACKGROUND: People with sickle cell disease (SCD) are at risk for accelerated biological aging and functional decline due to both age and SCD-related stressors. Frailty is characterized by decreased physiologic reserve and increased vulnerability to stress ... Full text Link to item Cite

Sickle red blood cell/Siglec-9 interactions contribute to neutrophil activation in SCD and are associated with survival

Journal Article Blood Red Cells & Iron · March 2026 Full text Cite

cellSTAAR: incorporating single-cell-sequencing-based functional data to boost power in rare variant association testing of noncoding regions.

Journal Article Nat Methods · February 2026 Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on th ... Full text Link to item Cite

Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications.

Journal Article Am J Hematol · December 2025 A deeper understanding of sickle cell disease (SCD) pathophysiology is critical for identifying novel therapeutic targets. A hallmark of SCD is abnormal phosphatidylserine (PS) exposure on sickle red blood cells (RBCs), which contributes to anemia, thrombo ... Full text Open Access Link to item Cite

Sickle cell disease is associated with early-onset clonal hematopoiesis involving DNA damage response pathway mutations

Conference Blood · November 3, 2025 AbstractBackground: Individuals with sickle cell disease (SCD) face an elevated risk of myeloid leukemias. Recently, myelodysplastic syndro ... Full text Cite

Basal and stimulated intra-RBC and exported ATP and RBC adhesivity ex vivo in children with sickle cell disease

Conference Blood · November 3, 2025 AbstractINTRODUCTIONSickle cell disease (SCD) represents a significant global health burden, and is characterized by hemolytic ... Full text Cite

Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.

Journal Article Genome Biol · September 9, 2025 BACKGROUND: Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohort ... Full text Open Access Link to item Cite

Genetic modifiers of frequent vaso-occlusive hospitalizations among individuals with sickle cell disease (SCD).

Journal Article Ann Hematol · August 2025 Sickle cell disease (SCD) is characterized by painful vaso-occlusive crises (VOC), which occur due to the adhesion of sickled erythrocytes and leukocytes to the endothelium, leading to vascular obstruction and tissue ischemia. Recurrent VOC increases SCD m ... Full text Open Access Link to item Cite

Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications.

Journal Article bioRxiv · May 31, 2025 A deeper understanding of sickle cell disease (SCD) pathophysiology is critical for identifying novel therapeutic targets. A hallmark of SCD is abnormal phosphatidylserine (PS) exposure on sickle red blood cells (RBCs), which contributes to anemia, thrombo ... Full text Link to item Cite

Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.

Journal Article Nat Commun · April 11, 2025 Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-geno ... Full text Link to item Cite

A replication study of novel fetal hemoglobin-associated genetic variants in sickle cell disease-only cohorts.

Journal Article Hum Mol Genet · April 6, 2025 Sickle cell disease (SCD) is the most common monogenic disease in the world and is caused by mutations in the β-globin gene (HBB). Notably, SCD is characterized by extreme clinical heterogeneity. Inter-individual variation in fetal hemoglobin (HbF) levels ... Full text Link to item Cite

Etavopivat reduces vaso-occlusive crisis incidence in sickle cell disease: HIBISCUS 2 week 52 results

Conference BRITISH JOURNAL OF HAEMATOLOGY · April 2025 Link to item Cite

The critical role of symptom experience on risk tolerance for gene therapy.

Journal Article Blood Adv · November 12, 2024 Full text Link to item Cite

Nontargeted Plasma Proteomic Analysis in Sickle Cell Disease Implicates Pathways Involving Cell Structure, Immunity and Heme and Oxygen Transport in the Occurrence of Leg Ulcers

Conference Blood · November 5, 2024 Background: Leg ulcers are a recurrent and debilitating complication of sickle cell disease (SCD), significantly impacting quality of life (QOL) and decreasing survival. The pathogenesis ... Full text Cite

Electronic Heath Record Phenotypes to Classify Sickle Cell Anemia Versus Other Subtypes of Sickle Cell Disease

Conference Blood · November 5, 2024 Introduction: Sickle cell disease (SCD) comprises a group of severe hemoglobinopathies caused by mutations in the β-globin gene (HBB) and includes sickle cell anemia (homozygous SCD, HbSS ... Full text Cite

Evaluation of the Role of PIEZO1 Genetic Variants in Red Blood Cell Health in Sickle Cell Disease

Conference Blood · November 5, 2024 BackgroundSickle cell disease (SCD) is a disorder arising from genetic variation in β-globin. Homozygosity for the sickle variant (HbSS) most commonly ... Full text Cite

Novel Loci Associated with Acute Chest Syndrome in Sickle Cell Disease Patients

Conference Blood · November 5, 2024 Sickle cell disease (SCD) results from a genetic mutation in the beta hemoglobin gene. Despite the same underlying causal mutation, patients exhibit highly heterogeneous clinical outcomes ... Full text Cite

Molecular Mechanism Underlying Excessive Phosphatidylserine Exposure in Sickle Red Blood Cells and Potential Therapeutics

Conference Blood · November 5, 2024 Background:Phosphatidylserine (PS) exposure on red blood cells (RBCs) promotes blood coagulation, enhances RBC adhesion to endothelial cells, and facil ... Full text Cite

Etavopivat Reduces Incidence of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: HIBISCUS Trial Phase 2 Results through 52 Weeks

Conference Blood · November 5, 2024 Background: Etavopivat is a potent, selective, once-daily, orally bioavailable activator of the red blood cell (RBC) pyruvate kinase isozyme, decreasing 2,3 DPG levels and increasing ATP ... Full text Cite

Red Cell Exchange Decreases Sickle RBC-Induced Release of MPO from Neutrophils

Conference Blood · November 5, 2024 Introduction: Neutrophil activation has long been recognized to contribute to sickle cell disease (SCD) pathophysiology. In prior studies, we have shown that patients with SCD have activa ... Full text Cite

A Phase 2 Prospective Randomized Trial of Topical Sodium Nitrite in Patients with Sickle Cell Disease and Leg Ulcers

Conference Blood · November 5, 2024 Background: Leg ulcers are a recurrent, painful and severe complication of sickle cell disease (SCD). Their occurrence significantly affects quality of life and is associated with decreas ... Full text Cite

Black Americans With Sickle Cell Disease (SCD) Demonstrate Accelerated Epigenetic Pace of Aging Compared to Black Americans Without SCD.

Journal Article J Gerontol A Biol Sci Med Sci · November 1, 2024 BACKGROUND: Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early ... Full text Link to item Cite

Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.

Journal Article Nat Commun · October 3, 2024 The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals fr ... Full text Link to item Cite

Standard Compared With Extended Red Blood Cell Antigen Matching for Prevention of Subsequent Hemolytic Disease of the Fetus and Newborn: A Systematic Review.

Journal Article Obstet Gynecol · October 1, 2024 OBJECTIVE: To systematically review and meta-analyze alloimmunization among recipients of red blood cells (RBCs) matched for ABO blood type and Rhesus D (ABO+D) antigen compared with those also matched for c, E, and Kell (cEK). DATA SOURCES: Four online da ... Full text Link to item Cite

Red cell exchange modulates neutrophil degranulation responses in sickle cell disease.

Journal Article Transfusion · September 2024 BACKGROUND: Neutrophils in sickle cell disease (SCD) are activated, contributing to disease. Red cell exchange (RCE), with the goal of lowering hemoglobin S (HbS), is an important part of therapy for many SCD patients. Whether RCE impacts neutrophil reacti ... Full text Link to item Cite

A genome-wide association study of alloimmunization in the TOPMed OMG-SCD cohort identifies a locus on chromosome 12.

Journal Article Transfusion · September 2024 BACKGROUND: Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantia ... Full text Open Access Link to item Cite

Multicenter, phase 1 study of etavopivat (FT-4202) treatment for up to 12 weeks in patients with sickle cell disease.

Journal Article Blood Adv · August 27, 2024 Etavopivat is an investigational, once daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study was conducted to characterize the safety and clinical activity of ... Full text Link to item Cite

Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.

Journal Article Nat Commun · May 24, 2024 Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry ... Full text Link to item Cite

Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.

Journal Article Lancet Haematol · May 2024 BACKGROUND: Although nitric oxide based therapeutics have been shown in preclinical models to reduce vaso-occlusive events and improve cardiovascular function, a clinical trial of a phosphodiesterase 5 inhibitor increased rates of admission to hospital for ... Full text Link to item Cite

Functions of blood group antigens

Chapter · March 8, 2024 This chapter reviews current knowledge about erythrocyte membrane proteins expressing blood group antigens. Known functions and physiologic roles are also reviewed. Primary attention is paid to two of the most highly expressed and interesting of these prot ... Full text Cite

Sickle red blood cells directly activate neutrophils.

Journal Article Br J Haematol · March 2024 Full text Link to item Cite

Nontargeted Plasma Proteomic Analysis of Renal Disease and Pulmonary Hypertension in Patients with Sickle Cell Disease.

Journal Article J Proteome Res · March 1, 2024 Sickle cell disease (SCD) is characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, damage to multiple organ systems, and, as a result, shortened life expectancy. Sickle cell disease nephropathy (SCDN) and pulmonary hypertension (pHTN) ... Full text Link to item Cite

PIEZO1-TMEM16F coupling in red blood disorders

Conference BIOPHYSICAL JOURNAL · February 8, 2024 Link to item Cite

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis.

Journal Article Blood · January 25, 2024 Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity ... Full text Link to item Cite

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis

Journal Article BLOOD · January 25, 2024 Full text Link to item Cite

Systematic review of recipient alloimmunization using standard ABO plus D versus an extended donor match protocol

Conference AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY · January 2024 Link to item Cite

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results.

Journal Article iScience · December 15, 2023 Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the ... Full text Link to item Cite

Preferences for potential benefits and risks for gene therapy in the treatment of sickle cell disease.

Journal Article Blood Adv · December 12, 2023 Objective of this study is to quantify benefit-risk tradeoffs pertaining to potential gene therapies among adults and parents/caregivers of children with sickle cell disease (SCD). A discrete-choice experiment survey was developed in which respondents sele ... Full text Link to item Cite

PIEZO1-TMEM16F Interplay in Hereditary Xerocytosis

Conference Blood · November 2, 2023 Cell surface exposure of phosphatidylserine (PS), an anionic phospholipid that is usually confined to the inner leaflet of the plasma membrane, triggers a plethora of cellular responses. PS exposure in RBCs contributes ... Full text Cite

Biologic Assessment of RBC Biology and Neutrophil Activation: Correlation with Sickle Cell Disease Activity

Conference Blood · November 2, 2023 Sickle cell disease (SCD) has pleiomorphic effects on affected individuals, most typically including both hemolysis and vaso-occlusive events (VOE). However, previous reports have suggested that these two paradigmatic p ... Full text Cite

Differences in the Circulating Proteome in Individuals with versus without Sickle Cell Trait.

Journal Article Clin J Am Soc Nephrol · November 1, 2023 BACKGROUND: Sickle cell trait affects approximately 8% of Black individuals in the United States, along with many other individuals with ancestry from malaria-endemic regions worldwide. While traditionally considered a benign condition, recent evidence sug ... Full text Link to item Cite

OA4-AM23-MN-36

Journal Article Transfusion · October 1, 2023 Full text Cite

Genome-wide meta-analysis identifies new candidate genes for sickle cell disease nephropathy.

Journal Article Blood Adv · September 12, 2023 Sickle cell disease nephropathy (SCDN), a common SCD complication, is strongly associated with mortality. Polygenic risk scores calculated from recent transethnic meta-analyses of urinary albumin-to-creatinine ratio and estimated glomerular filtration rate ... Full text Link to item Cite

Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma.

Journal Article EBioMedicine · September 2023 BACKGROUND: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. METHODS: We performed an epigenome-wide association study us ... Full text Link to item Cite

WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE.

Journal Article medRxiv · August 22, 2023 Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-geno ... Full text Link to item Cite

Author Correction: Clonal haematopoiesis and risk of chronic liver disease.

Journal Article Nature · July 2023 Full text Link to item Cite

Sex differences in progression of kidney disease in sickle cell disease.

Journal Article Haematologica · May 1, 2023 Full text Link to item Cite

Management of Older Adults with Sickle Cell Disease: Considerations for Current and Emerging Therapies.

Journal Article Drugs Aging · April 2023 People with sickle cell disease (SCD) are living longer than ever before, with the median survival increasing from age 14 years in 1973, beyond age 40 years in the 1990s, and as high as 61 years in recent cohorts from academic centers. Improvements in surv ... Full text Link to item Cite

Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.

Journal Article Nature · April 2023 Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, par ... Full text Link to item Cite

Clonal haematopoiesis and risk of chronic liver disease.

Journal Article Nature · April 2023 Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examin ... Full text Link to item Cite

Genetic regulation of fetal hemoglobin across global populations.

Journal Article medRxiv · March 28, 2023 Human genetic variation has enabled the identification of several key regulators of fetal-to-adult hemoglobin switching, including BCL11A, resulting in therapeutic advances. However, despite the progress made, limited further insights have been obtained to ... Full text Link to item Cite

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results.

Journal Article bioRxiv · March 24, 2023 Studies combining metabolomics and genetics, known as metabolite genome-wide association studies (mGWAS), have provided valuable insights into our understanding of the genetic control of metabolite levels. However, the biological interpretation of these as ... Full text Link to item Cite

Variation and impact of polygenic hematologic traits in monogenic sickle cell disease.

Journal Article Haematologica · March 1, 2023 Several of the complications observed in sickle cell disease (SCD) are influenced by variation in hematologic traits (HT), such as fetal hemoglobin (HbF) level and neutrophil count. Previous large-scale genome-wide association studies carried out in largel ... Full text Link to item Cite

Structural variation across 138,134 samples in the TOPMed consortium.

Journal Article Res Sq · February 3, 2023 Ever larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a bala ... Full text Link to item Cite

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.

Journal Article Nat Genet · February 2023 Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative ... Full text Link to item Cite

Structural variation across 138,134 samples in the TOPMed consortium.

Journal Article bioRxiv · January 25, 2023 Ever larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a bala ... Full text Link to item Cite

A randomized clinical trial of the efficacy and safety of rivipansel for sickle cell vaso-occlusive crisis.

Journal Article Blood · January 12, 2023 The efficacy and safety of rivipansel, a predominantly E-selectin antagonist, were studied in a phase 3, randomized, controlled trial for vaso-occlusive crisis (VOC) requiring hospitalization (RESET). A total of 345 subjects (204 adults and 141 children) w ... Full text Link to item Cite

Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies.

Journal Article Nat Genet · January 2023 Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-a ... Full text Open Access Link to item Cite

Genetic Modifiers of Sickle Cell Disease.

Journal Article Hematol Oncol Clin North Am · December 2022 Sickle cell disease (SCD) is characterized by tremendous phenotypic heterogeneity across patients, but this clinical variability is poorly understood, thus motivating the search for genetic modifiers. The early identification of genetic variants that contr ... Full text Link to item Cite

Genetic diversity fuels gene discovery for tobacco and alcohol use.

Journal Article Nature · December 2022 Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies ... Full text Open Access Link to item Cite

A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies.

Journal Article Nat Methods · December 2022 Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limite ... Full text Open Access Link to item Cite

Rare genetic variants explain missing heritability in smoking.

Journal Article Nat Hum Behav · November 2022 Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with ... Full text Link to item Cite

Design, Synthesis, and Investigation of Novel Nitric Oxide (NO)-Releasing Aromatic Aldehydes as Drug Candidates for the Treatment of Sickle Cell Disease.

Journal Article Molecules · October 12, 2022 Sickle cell disease (SCD) is caused by a single-point mutation, and the ensuing deoxygenation-induced polymerization of sickle hemoglobin (HbS), and reduction in bioavailability of vascular nitric oxide (NO), contribute to the pathogenesis of the disease. ... Full text Link to item Cite

Whole genome sequence analysis of blood lipid levels in >66,000 individuals.

Journal Article Nat Commun · October 11, 2022 Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly ... Full text Open Access Link to item Cite

Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.

Journal Article Nat Commun · August 22, 2022 Integrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage gen ... Full text Link to item Cite

Longitudinal study of glomerular hyperfiltration in adults with sickle cell anemia: a multicenter pooled analysis.

Journal Article Blood Adv · August 9, 2022 Glomerular hyperfiltration is common in young sickle cell anemia patients and precedes development of overt kidney disease. In this multicenter pooled cohort, we characterized hyperfiltration and its decline to normal range in adult patients. Glomerular fi ... Full text Link to item Cite

Etavopivat, an investigational, once-daily, selective pyruvate kinase-R activator, improves sickle red blood cell health and survival in patients with sickle cell disease: an analysis of exploratory studies in a phase 1 trial

Conference BRITISH JOURNAL OF HAEMATOLOGY · April 2022 Link to item Cite

Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data.

Journal Article Nat Genet · March 2022 Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining ... Full text Link to item Cite

Clonal hematopoiesis in sickle cell disease.

Journal Article J Clin Invest · February 15, 2022 BACKGROUNDCurative gene therapies for sickle cell disease (SCD) are currently undergoing clinical evaluation. The occurrence of myeloid malignancies in these trials has prompted safety concerns. Individuals with SCD are predisposed to myeloid malignancies, ... Full text Link to item Cite

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.

Journal Article Cell Genom · January 12, 2022 Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally ... Full text Link to item Cite

Author Correction: A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response.

Journal Article Nat Genet · December 2021 Full text Link to item Cite

Etavopivat, an Allosteric Activator of Pyruvate Kinase-R, Improves Sickle RBC Functional Health and Survival and Reduces Systemic Markers of Inflammation and Hypercoagulability in Patients with Sickle Cell Disease: An Analysis of Exploratory Studies in a Phase 1 Study

Conference Blood · November 5, 2021 AbstractThe hallmark of sickle cell disease (SCD) is polymerization of deoxygenated hemoglobin S (HbS), resulting in red blood cell (RBC) sickling, oxidative and membrane damage, hemolysis, vaso-occlusion, a ... Full text Cite

Activation of Pyruvate Kinase-R with Etavopivat (FT-4202) Is Well Tolerated, Improves Anemia, and Decreases Intravascular Hemolysis in Patients with Sickle Cell Disease Treated for up to 12 Weeks

Conference Blood · November 5, 2021 AbstractEtavopivat is a small molecule activator of erythrocyte pyruvate kinase (PKR), that increases PKR activity, resulting in decreased 2,3-DPG and increased ATP in red blood cells (RBCs) of healthy volun ... Full text Cite

Identification of optimal thalassemia screening strategies for migrant populations in Thailand using a qualitative approach.

Journal Article BMC Public Health · October 6, 2021 BACKGROUND: Thalassemia is a common inherited hemoglobin disorder in Southeast Asia. Severe thalassemia can lead to significant morbidity for patients and economic strain for under-resourced health systems. Thailand's thalassemia prevention and control pro ... Full text Link to item Cite

A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response.

Journal Article Nat Genet · October 2021 Fine-mapping to plausible causal variation may be more effective in multi-ancestry cohorts, particularly in the MHC, which has population-specific structure. To enable such studies, we constructed a large (n = 21,546) HLA reference panel spanning five glob ... Full text Link to item Cite

Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.

Journal Article Genome Med · August 26, 2021 BACKGROUND: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we p ... Full text Link to item Cite

Feasibility of and barriers to thalassemia screening in migrant populations: a cross-sectional study of Myanmar and Cambodian migrants in Thailand.

Journal Article BMC Public Health · June 21, 2021 BACKGROUND: Thalassemia, an inherited hemoglobin disorder, has become a global public health problem due to population migration. Evidence-based strategies for thalassemia prevention in migrants are lacking. We characterized barriers to thalassemia screeni ... Full text Link to item Cite

Genome sequencing unveils a regulatory landscape of platelet reactivity.

Journal Article Nat Commun · June 15, 2021 Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3, ... Full text Link to item Cite

Variant-specific inflation factors for assessing population stratification at the phenotypic variance level.

Journal Article Nat Commun · June 9, 2021 In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we te ... Full text Link to item Cite

Rapid decline in estimated glomerular filtration rate in sickle cell anemia: results of a multicenter pooled analysis.

Journal Article Haematologica · June 1, 2021 Not available. ... Full text Link to item Cite

Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium.

Journal Article Genome Med · April 21, 2021 BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be ... Full text Link to item Cite

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.

Journal Article Nat Commun · April 12, 2021 Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-cov ... Full text Link to item Cite

FT-4202, an allosteric activator of pyruvate kinase-R, demonstrates proof of mechanism and proof of concept after multiple daily doses in a phase 1 study of patients with sickle cell disease

Conference BRITISH JOURNAL OF HAEMATOLOGY · April 2021 Link to item Cite

Hibiscus, an adaptive, randomized, placebo-controlled, double-blind, multi-centre study of oral FT-4202, a pyruvate kinase activator in patients with sickle cell disease

Conference BRITISH JOURNAL OF HAEMATOLOGY · April 2021 Link to item Cite

Author Correction: Inherited causes of clonal haematopoiesis in 97,691 whole genomes.

Journal Article Nature · March 2021 Full text Link to item Cite

Potential causal role of l-glutamine in sickle cell disease painful crises: A Mendelian randomization analysis.

Journal Article Blood Cells Mol Dis · February 2021 In a recent clinical trial, the metabolite l-glutamine was shown to reduce painful crises in sickle cell disease (SCD) patients. To support this observation and identify other metabolites implicated in SCD clinical heterogeneity, we profiled 129 metabolite ... Full text Link to item Cite

Diversity of variant alleles encoding Kidd, Duffy, and Kell antigens in individuals with sickle cell disease using whole genome sequencing data from the NHLBI TOPMed Program.

Journal Article Transfusion · February 2021 BACKGROUND: Genetic variants in the SLC14A1, ACKR1, and KEL genes, which encode Kidd, Duffy, and Kell red blood cell antigens, respectively, may result in weakened expression of antigens or a null phenotype. These variants are of particular interest to ind ... Full text Link to item Cite

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

Journal Article Nature · February 2021 The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The init ... Full text Link to item Cite

Clonal hematopoiesis in sickle cell disease

Journal Article · 2021 Curative gene therapies for sickle cell disease (SCD) are currently undergoing clinical evaluation. However, the occurrence of several myeloid malignancy cases in these trials has prompted safety concerns. Individuals with SCD are predisposed to myeloid ma ... Full text Cite

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Journal Article Nat Commun · December 18, 2020 Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide anal ... Full text Link to item Cite

Genome Wide Association Analysis of Iron Overload in the Trans-Omics for Precision Medicine (TOPMed) Sickle Cell Disease Cohorts

Conference Blood · November 5, 2020 Introduction: Transfusional iron (Fe) overload is a significant problem among patients with chronic, transfusion-dependent anemias. Iron overload is an important problem in pediatric sickle cell disease (SCD) patients on chronic transfusion regimen ... Full text Cite

Pyridoxamine: another vitamin for sickle cell disease?

Journal Article Haematologica · October 1, 2020 Full text Link to item Cite

Inherited causes of clonal haematopoiesis in 97,691 whole genomes.

Journal Article Nature · October 2020 Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic s ... Full text Link to item Cite

Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale.

Journal Article Nat Genet · September 2020 Large-scale whole-genome sequencing studies have enabled the analysis of rare variants (RVs) associated with complex phenotypes. Commonly used RV association tests have limited scope to leverage variant functions. We propose STAAR (variant-set test for ass ... Full text Link to item Cite

Curative vs targeted therapy for SCD: does it make more sense to address the root cause than target downstream events?

Journal Article Blood Adv · July 28, 2020 Sickle cell disease (SCD) places a heavy burden on a global and increasing population predominantly resident in resource-poor and developing countries. Progress continues to be made in preventing childhood mortality, and increasing numbers of chronically i ... Full text Link to item Cite

Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Journal Article Nat Commun · April 1, 2020 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Serum albumin is independently associated with higher mortality in adult sickle cell patients: Results of three independent cohorts.

Journal Article PLoS One · 2020 Sickle cell disease (SCD) impacts liver and kidney function as well as skin integrity. These complications, as well as the hyperinflammatory state of SCD, could affect serum albumin. Serum albumin has key roles in antioxidant, anti-inflammatory and antithr ... Full text Link to item Cite

Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma.

Conference Chest · December 2019 BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function ... Full text Link to item Cite

Phase 1 Single (SAD) and Multiple Ascending Dose (MAD) Studies of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of FT-4202, an Allosteric Activator of Pyruvate Kinase-R, in Healthy and Sickle Cell Disease Subjects

Conference Blood · November 13, 2019 Background: The hallmark of sickle cell disease (SCD) is hemoglobin S (HbS) polymerization upon deoxygenation, resulting in red blood cell (RBC) sickling, oxidative damage, membrane damage, hemolysis, chronic anemia, vaso-occlusions and inflammatio ... Full text Cite

Identification of Optimal Thalassemia Screening Strategies for Migrant Populations in Thailand: A Mixed-Methods Approach

Conference Blood · November 13, 2019 BACKGROUND: Severe thalassemia is common in Southeast Asia (SEA) and can lead to transfusion dependent anemia, growth retardation, and perinatal death. Prevention and control of thalassemia can be approached either preconceptionally (through carrie ... Full text Cite

Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.

Journal Article Blood Adv · September 10, 2019 Sickle red blood cells (SSRBCs) are adherent to the endothelium, activate leukocyte adhesion, and are deficient in bioactive nitric oxide (NO) adducts such as S-nitrosothiols (SNOs), with reduced ability to induce vasodilation in response to hypoxia. All t ... Full text Open Access Link to item Cite

A multi-institutional comparison of younger and older adults with sickle cell disease.

Journal Article Am J Hematol · April 2019 Full text Link to item Cite

Therapeutic strategies for sickle cell disease: towards a multi-agent approach.

Journal Article Nat Rev Drug Discov · February 2019 For over 100 years, clinicians and scientists have been unravelling the consequences of the A to T substitution in the β-globin gene that produces haemoglobin S, which leads to the systemic manifestations of sickle cell disease (SCD), including vaso-occlus ... Full text Link to item Cite

RNA sequencing of isolated cell populations expressing human APOL1 G2 risk variant reveals molecular correlates of sickle cell nephropathy in zebrafish podocytes.

Conference PLoS One · 2019 Kidney failure occurs in 5-13% of individuals with sickle cell disease and is associated with early mortality. Two APOL1 alleles (G1 and G2) have been identified as risk factors for sickle cell disease nephropathy. Both risk alleles are prevalent in indivi ... Full text Link to item Cite

Functions of blood group antigens

Chapter · January 1, 2019 This chapter reviews knowledge about erythrocyte membrane proteins that bear blood group antigens and whose functional importance has been characterized. It focuses on two of the most interesting of these proteins: the anion exchanger protein, which bears ... Full text Cite

Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.

Journal Article Am J Hematol · December 2018 Sickle cell disease (SCD) nephropathy and lower estimated glomerular filtration rate (eGFR) are risk factors for early mortality. Furthermore, rate of eGFR decline predicts progression to end-stage renal disease in many clinical settings. However, factors ... Full text Link to item Cite

Knowledge, Cultural, and Structural Barriers to Thalassemia Screening in Migrant Populations in Thailand

Conference Blood · November 29, 2018 AbstractBACKGROUND: Thalassemia syndromes are inherited hemoglobin (Hb) disorders that most severely affect Southeast Asia (SEA). As a result of population migration, thalassemia has grown into a global heal ... Full text Cite

A common functional PIEZO1 deletion allele associates with red blood cell density in sickle cell disease patients.

Journal Article Am J Hematol · November 2018 Full text Link to item Cite

Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Journal Article Nat Commun · August 23, 2018 The original version of this article contained an error in the name of the author Ramachandran S. Vasan, which was incorrectly given as Vasan S. Ramachandran. This has now been corrected in both the PDF and HTML versions of the article. ... Full text Link to item Cite

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Journal Article Nat Commun · August 23, 2018 Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-p ... Full text Link to item Cite

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Journal Article Nat Commun · July 4, 2018 Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use d ... Full text Link to item Cite

Depression, quality of life, and medical resource utilization in sickle cell disease.

Journal Article Blood Adv · October 24, 2017 Sickle cell disease (SCD) is a chronic, debilitating disorder. Chronically ill patients are at risk for depression, which can affect health-related quality of life (HRQoL), health care utilization, and cost. We performed an analytic epidemiologic prospecti ... Full text Open Access Link to item Cite

Thrombospondin-1 gene polymorphism is associated with estimated pulmonary artery pressure in patients with sickle cell anemia.

Journal Article Am J Hematol · March 2017 Full text Link to item Cite

Developing new pharmacotherapeutic approaches to treating sickle-cell disease.

Journal Article ISBT Sci Ser · February 2017 Survival for patients with SCD has been prolonged by improvements in supportive care, including vaccinations, antibiotic prophylaxis, and overall medical management, including tra nsfusion. However, there remains only one approved, partially effective drug ... Full text Link to item Cite

Communications: To contributors to the 2017 issues

Journal Article Immunohematology · January 1, 2017 Cite

Thrombospondin-1 Polymorphisms Are Associated with Chronic Kidney Disease in Sickle Cell Anemia

Conference Blood · December 2, 2016 AbstractBackground: Sickle cell anemia (SCA) is characterized by the "sickling" of red blood cells (RBCs) and red cell rigidity, as well as increased cellular adhesiveness of blood cells and endothelium, lea ... Full text Cite

Factors Related to the Progression of Sickle Cell Disease Nephropathy

Conference Blood · December 2, 2016 AbstractBACKGROUND: As life expectancy in sickle cell disease (SCD) has continued to increase, chronic diseases are playing a bigger role in morbidity and mortality in this population. SCD nephropathy is a k ... Full text Cite

GWAS Meta-Analysis of Glomerular Filtration Rate in Three Cohorts of Sickle Cell Disease Patients and In Vivo Functional Analysis Reveals Potential Nephropathy Candidate Genes

Conference Blood · December 2, 2016 AbstractBACKGROUND: Sickle cell disease nephropathy (SCDN) is a common complication of sickle cell disease (SCD) associated with risk for early mortality (Platt et al., 1994; Elmari ... Full text Cite

Use of Mobile Technology to Monitor Pain and Reduce Outpatient, Emergency Department (ED), and Hospital Visits for Sickle Cell Pain Crisis

Conference Blood · December 2, 2016 AbstractIntroduction: Sickle cell disease (SCD) is a chronic illness associated with frequent medical complications and hospitalizations. Importantly, approximately ninety percent of hospitalizations are for ... Full text Cite

Effect of FXIII Polymorphism on Formation of Heterocellular Aggregates in SCD

Conference Blood · December 2, 2016 AbstractBACKGROUND: We have recently identified a SNP (rs5988) in the gene encoding the factor XIII A chain (F13A) that is highly associated with risk for priapism in SCD. The P val ... Full text Cite

Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.

Journal Article Br J Haematol · December 2016 Sevuparin is a novel drug candidate in phase II development as a treatment for vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, whil ... Full text Link to item Cite

Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease.

Journal Article Blood · February 18, 2016 Despite Food and Drug Administration (FDA) approval of hydroxyurea to reduce the frequency of vaso-occlusive episodes, sickle cell disease (SCD) has continued to be treated primarily with analgesics for pain relief. However, elucidation of the multiple pat ... Full text Link to item Cite

Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease.

Journal Article PLoS One · 2016 Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-deri ... Full text Link to item Cite

Genome-Wide Evaluation of Epistasis with APOL1 Risk Variants in Sickle Cell Disease Nephropathy

Conference BLOOD · December 3, 2015 Link to item Cite

A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes.

Journal Article BMC Genomics · November 16, 2015 BACKGROUND: Human erythrocytes are terminally differentiated, anucleate cells long thought to lack RNAs. However, previous studies have shown the persistence of many small-sized RNAs in erythrocytes. To comprehensively define the erythrocyte transcriptome, ... Full text Link to item Cite

Validation of a novel point of care testing device for sickle cell disease.

Journal Article BMC Med · September 16, 2015 BACKGROUND: Sickle cell disease is one of the most common inherited blood disorders. Universal screening and early intervention have significantly helped to reduce childhood mortality in high-resource countries. However, persons living in low-resource sett ... Full text Link to item Cite

Correction: In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress.

Journal Article PLoS Genet · September 2015 Full text Link to item Cite

In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress.

Journal Article PLoS Genet · July 2015 African Americans have a disproportionate risk for developing nephropathy. This disparity has been attributed to coding variants (G1 and G2) in apolipoprotein L1 (APOL1); however, there is little functional evidence supporting the role of this protein in r ... Full text Open Access Link to item Cite

Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival.

Journal Article Transfusion · June 2015 BACKGROUND: Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization ... Full text Link to item Cite

Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use.

Journal Article Blood · April 23, 2015 Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and a ... Full text Link to item Cite

Biomarkers and recent advances in the management and therapy of sickle cell disease.

Journal Article F1000Res · 2015 Although production of hemoglobin S, the genetic defect that causes sickle cell disease (SCD), directly affects only red blood cells, the manifestations of SCD are pervasive, and almost every cell type and organ system in the body can be involved. Today, t ... Full text Link to item Cite

Genes Associated with Survival in Adult Sickle Cell Disease

Conference BLOOD · December 6, 2014 Link to item Cite

Evidence for a Dominant Negative Effect Conferred By the APOL1 G2 Sickle Cell Nephropathy Risk Allele in an in Vivo Model

Conference BLOOD · December 6, 2014 Link to item Cite

Genome-Wide Association Study of Glomerular Filtration Rate in a Cohort of Sickle Cell Disease Patients

Conference BLOOD · December 6, 2014 Link to item Cite

Genes Associated with Alloimmunization to Blood Group Antigens in Sickle Cell Disease

Conference BLOOD · December 6, 2014 Link to item Cite

Effects of Sulforaphane Obtained from Broccoli Sprout Homogenate in Patients with Sickle Cell Disease (SCD)

Conference BLOOD · December 6, 2014 Link to item Cite

Pan-Selectin Antagonist Rivipansel (GMI-1070) Reduces Soluble E-Selectin Levels While Improving Clinical Outcomes in SCD Vaso-Occlusive Crisis

Conference Blood · December 6, 2014 AbstractIntroduction: The pan-selectin antagonist rivipansel (GMI-1070) reduced intravascular arrest of red/white blood cell aggregates and improved blood flow and survival in a mouse model of sickle cell di ... Full text Cite

Erratum: Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia (PLoS ONE (2014) 9, 7 (e101301) DOI:10.1371/journal.pone.0101301)

Journal Article Plos One · October 17, 2014 Full text Cite

Reply: Practice guideline for pulmonary hypertension in sickle cell: direct evidence needed before universal adoption.

Journal Article Am J Respir Crit Care Med · July 15, 2014 Full text Link to item Cite

Factors associated with survival in a contemporary adult sickle cell disease cohort.

Journal Article Am J Hematol · May 2014 In this study, the relationship of clinical differences among patients with sickle cell disease (SCD) was examined to understand the major contributors to early mortality in a contemporary cohort. Survival data were obtained for 542 adult subjects who were ... Full text Link to item Cite

Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors.

Journal Article Hematol Oncol Clin North Am · April 2014 The pathophysiology of vasoocclusion is thought to involve a wide variety of adhesive interactions involving erythrocytes, leukocytes, and the endothelium. Selectins are expressed by leukocytes, platelets, and the endothelium, among other tissues. They con ... Full text Link to item Cite

An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease.

Journal Article Am J Respir Crit Care Med · March 15, 2014 BACKGROUND: In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) di ... Full text Link to item Cite

Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors

Journal Article Hematology/Oncology Clinics of North America · 2014 Cite

Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia.

Journal Article PLoS One · 2014 BACKGROUND: Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion se ... Full text Link to item Cite

Teaching evidence-based medicine in the former Soviet Union: lessons learned.

Journal Article Trans Am Clin Climatol Assoc · 2014 Between 2009 and 2012, I taught principles of evidence-based medicine and clinical research in Russia, Tatarstan, Moldova, and Kazakhstan. The Soviet Union left a medical legacy characterized by balkanization of top tier medicine in highly specialized cent ... Link to item Cite

GMI 1070: Reduction In Time To Resolution Of Vaso-Occlusive Crisis and Decreased Opioid Use In a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase 2 Study In Sickle Cell Disease

Conference Blood · November 15, 2013 AbstractBackgroundTreatment for vaso-occlusive crisis (VOC) in sickle cell disease (SCD) remains supportive, focusing largely on sympt ... Full text Cite

Effects Of GMI 1070, a Pan-Selectin Inhibitor, On Pain Intensity and Opioid Utilization In Sickle Cell Disease

Conference Blood · November 15, 2013 AbstractBackgroundManagement of acute, painful vaso-occlusive crisis (VOC), the hallmark of sickle cell dise ... Full text Cite

In Vivo Modeling Of Genetic Mechanisms Associated With Sickle Cell Disease Nephropathy

Conference Blood · November 15, 2013 AbstractEnd-organ damage in patients with sickle cell disease (SCD) has become an emergent clinical priority over recent decades due to the increased lifespan of affected individuals. Renal failure (ESRD), w ... Full text Cite

Sevuparin Reduces Adhesion Of Both Sickle Red Cells and Leukocytes To Endothelial Cells In Vitro and Inhibits Vaso-Occlusion In Vivo

Conference Blood · November 15, 2013 AbstractIntroductionSevuparin is a new chemically modified heparin with low anticoagulant activity currently being studied as an adjuv ... Full text Cite

Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients.

Journal Article Blood · July 18, 2013 Patients with sickle cell disease (SCD) present with a wide range of clinical complications. Understanding this clinical heterogeneity offers the prospects to tailor the right treatments to the right patients and also guide the development of novel therapi ... Full text Link to item Cite

IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies.

Journal Article Clin Trials · April 2013 BACKGROUND: The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The ... Full text Link to item Cite

Sickle erythrocytes target cytotoxics to hypoxic tumor microvessels and potentiate a tumoricidal response.

Journal Article PLoS One · 2013 Resistance of hypoxic solid tumor niches to chemotherapy and radiotherapy remains a major scientific challenge that calls for conceptually new approaches. Here we exploit a hitherto unrecognized ability of sickled erythrocytes (SSRBCs) but not normal RBCs ... Full text Open Access Link to item Cite

Effect of propranolol as antiadhesive therapy in sickle cell disease.

Journal Article Clin Transl Sci · December 2012 Sickle red blood cells (SSRBCs) adhere to both endothelial cells (ECs) and the extracellular matrix. Epinephrine elevates cyclic adenosine monophosphate in SSRBCs and increases adhesion of SSRBCs to ECs in a β-adrenergic receptor and protein kinase A-depen ... Full text Link to item Cite

Pan-Selectin Antagonist GMI-1070 Affects Biomarkers of Adhesion, Activation and the Coagulation Cascade in Sickle Cell Adults At Steady State

Conference Blood · November 16, 2012 AbstractAbstract 87Introduction:Engagement of selectins by their ligands leads to cellular activation ... Full text Cite

Characterization of the hypercoagulable state in patients with sickle cell disease.

Journal Article Thromb Res · November 2012 BACKGROUND: The pathophysiology of sickle cell disease (SCD) is complex, with increasing evidence of a pronounced prothrombotic state. OBJECTIVE: We investigated thrombin generation in SCD utilizing calibrated automated thrombography (CAT) and D-dimer, wit ... Full text Link to item Cite

Meta-analysis of 2040 sickle cell anemia patients: BCL11A and HBS1L-MYB are the major modifiers of HbF in African Americans.

Journal Article Blood · August 30, 2012 Full text Link to item Cite

Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance.

Journal Article Cell Host Microbe · August 16, 2012 Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains ... Full text Link to item Cite

Mechanisms behind adhesive erythrocytes in sickle‐cell disease

Journal Article ISBT Science Series · July 2012 Erythrocytes containing primarily hemoglobin S (SS RBCs) are abnormally adherent to a number of ligands, including normal constituents of the extracellular matrix as well as those present on the surfaces of other blood cells and endothelial cells. ... Full text Cite

Nitric oxide deficiency in sickle red cells is associated with increased cell adhesion to endothelium and vaso-occlusion

Conference Nitric Oxide · July 2012 Full text Cite

GMI-1070: Pan-selectin antagonist treatment of sickle cell disease

Journal Article Drugs of the Future · June 1, 2012 GMI-1070 is a rationally designed carbohydrate molecule created as an antagonist of all selectin proteins. Selectins are adhesion molecules expressed by many hematopoietic and endothelial cells. They mediate early stages of cell adhesion and are therefore ... Full text Cite

Dynamic quantitative microscopy and nanoscopy of red blood cells in sickle cell disease

Conference Progress in Biomedical Optics and Imaging Proceedings of SPIE · April 16, 2012 We have applied wide-field digital interferometric techniques to quantitatively image sickle red blood cells (RBCs) [1] in a noncontact label-free manner, and measure the nanometer-scale fluctuations in their thickness as an indication of their stiffness. ... Full text Cite

Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.

Journal Article Blood · February 2, 2012 The core pathology of sickle cell disease (SCD) starts with the erythrocyte (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion, occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted that ERK1/2 is funct ... Full text Link to item Cite

Novel optical signature for sickle cell trait red blood cells

Journal Article Frontiers in Optics Fio 2012 · January 1, 2012 We identified unique optical signatures for sickle cell trait, a condition where heterozygous individuals are carriers for the hemoglobin allele that causes sickle cell anemia, by using wide-field interferometric microscopy. © OSA 2012. ... Full text Cite

GMI-1070: Pan-selectin antagonist treatment of sickle cell disease

Journal Article Drugs of the Future · January 1, 2012 GMI-1070 is a rationally designed carbohydrate molecule created as an antagonist of all selectin proteins. Selectins are adhesion molecules expressed by many hematopoietic and endothelial cells. They mediate early stages of cell adhesion and are therefore ... Full text Cite

A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.

Journal Article PLoS One · 2012 Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubi ... Full text Link to item Cite

Kikuchi-Fugimoto's disease in sickle cell disease: report of 2 cases.

Journal Article J Natl Med Assoc · 2012 Kikuchi-Fugimoto's Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is most frequently seen in young women and has been associated with autoimmune disorders such as polymyositis and systemic lupus erythematosus. It is generally a self-li ... Full text Link to item Cite

Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

Journal Article Am J Hematol · December 2011 Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better ... Full text Link to item Cite

An Elevated Tricuspid Regurgitant Jet Velocity in Sickle Cell Disease Is Associated with Polymorphisms in Genes Impacting Innate Immunity

Conference BLOOD · November 18, 2011 Link to item Cite

Inflammatory Polymorphisms Link the Risk of Acute Chest Syndrome with Asthma in Adults with Sickle Cell Disease

Conference BLOOD · November 18, 2011 Link to item Cite

Sickle Red Blood Cell Induced Adhesion of Neutrophils to Endothelial Cells and Biologic Correlates of Leukocyte Activation

Conference Blood · November 18, 2011 Abstract 1055In sickle cell disease (SCD), any event that slows the passage of red blood cells (RBCs) in the microcirculation can promote hemoglobin polymerization, red cell sickling, and vaso-occlusion. Homozygous ... Full text Cite

Impaired adenosine-5'-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion.

Journal Article Crit Care Med · November 2011 OBJECTIVE: Transfusion of red blood cells has been linked to disappointing clinical outcomes in the critically ill, but specific mechanisms of organ dysfunction after transfusion remain poorly understood. We tested the hypothesis that red blood cell storag ... Full text Link to item Cite

MYH9 and APOL1 are both associated with sickle cell disease nephropathy.

Journal Article Br J Haematol · November 2011 Renal failure occurs in 5-18% of sickle cell disease (SCD) patients and is associated with early mortality. At-risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The myosin, heavy chai ... Full text Link to item Cite

Erratum: Costs and length of stay for patients with and without sickle cell disease after hysterectomy, appendectomy, or knee replacement

Journal Article American Journal of Hematology · October 1, 2011 Full text Cite

Erratum: Outcomes of inpatients with and without sickle cell disease after high-volume surgical procedures

Journal Article American Journal of Hematology · October 1, 2011 Full text Cite

RNA aptamer therapy for vaso-occlusion in sickle cell disease.

Journal Article Nucleic Acid Ther · August 2011 Patients with sickle cell disease (SCD) often suffer painful vaso-occlusive episodes caused in part by the adhesion of sickle erythrocytes (SS-RBC) to the vascular endothelium. To investigate inhibition of SS-RBC adhesion as a possible treatment for vaso-o ... Full text Link to item Cite

Evaluation of thrombin generation in sickle cell patients and correlation to clinical disease

Journal Article JOURNAL OF THROMBOSIS AND HAEMOSTASIS · July 1, 2011 Link to item Cite

Comparison of thrombin generation of sickle cell patients in crisis and steady state using the thrombin generation assay (TGA)

Journal Article HAEMOPHILIA · May 1, 2011 Link to item Cite

Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry.

Journal Article J Biomed Opt · March 2011 We have applied wide-field digital interferometry (WFDI) to examine the morphology and dynamics of live red blood cells (RBCs) from individuals who suffer from sickle cell anemia (SCA), a genetic disorder that affects the structure and mechanical propertie ... Full text Link to item Cite

The effects of hydroxycarbamide and magnesium on haemoglobin SC disease: results of the multi-centre CHAMPS trial.

Journal Article Br J Haematol · March 2011 In a phase-II multi-centre double-blinded trial, we evaluated haematological effects of oral hydroxycarbamide (HC) and magnesium (Mg) in patients with HbSC, aged 5-53 years old. Subjects were randomized to HC + placebo, Mg + placebo, HC + Mg, or placebo + ... Full text Link to item Cite

Red Blood Cell Release Of ATP Prevents Endothelial Adhesion: Implications For Post-Transfusion Lung Dysfunction

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2011 Link to item Cite