Michael Bradley Datto

Journal article J Mol Diagn · July 2010 Featured Publication Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pedi ... Full text Open Access Link to item Cite

SMAD4 is required for development of maximal endotoxin tolerance.

Journal article J Immunol · May 15, 2010 Featured Publication Initial exposure of monocytes/macrophages to LPS induces hyporesponsiveness to a second challenge with LPS, a phenomenon termed LPS tolerance. Molecular mechanisms responsible for endotoxin tolerance are not well defined. We and others have shown that IL-1 ... Full text Link to item Cite

Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome.

Journal article J Clin Oncol · May 1, 2010 Featured Publication PURPOSE: Identifying sources of variation in expression microarray data and the effect of variance in gene expression measurements on complex predictive and diagnostic models is essential when translating microarray-based experimental approaches into clini ... Full text Link to item Cite

A pathway-based classification of human breast cancer.

Journal article Proc Natl Acad Sci U S A · April 13, 2010 Featured Publication The hallmark of human cancer is heterogeneity, reflecting the complexity and variability of the vast array of somatic mutations acquired during oncogenesis. An ability to dissect this heterogeneity, to identify subgroups that represent common mechanisms of ... Full text Link to item Cite

NDRG4 is required for cell cycle progression and survival in glioblastoma cells.

Journal article J Biol Chem · September 11, 2009 Featured Publication NDRG4 is a largely unstudied member of the predominantly tumor suppressive N-Myc downstream-regulated gene (NDRG) family. Unlike its family members NDRG1-3, which are ubiquitously expressed, NDRG4 is expressed almost exclusively in the heart and brain. Giv ... Full text Link to item Cite

Chordoid glioma: a case report and molecular characterization of five cases.

Journal article Brain Pathol · July 2009 Featured Publication Chordoid gliomas are rare, slow-growing neoplasms of the anterior third ventricle. We reported a case of chordoid glioma in a 41-year-old man with obstructive hydrocephalus. Histologically, the tumor consisted of polygonal epithelioid cells admixed with el ... Full text Link to item Cite

Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle.

Journal article J Biol Chem · April 25, 2008 Featured Publication In vivo protein kinases A and G (PKA and PKG) coordinately phosphorylate a broad range of substrates to mediate their various physiological effects. The functions of many of these substrates have yet to be defined genetically. Herein we show a role for smo ... Full text Link to item Cite

Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.

Journal article Genes Dev · February 1, 2008 Featured Publication Metastasis, the major cause of cancer death, is a multistep process that requires interactions between cancer cells and stromal cells and between cancer cells and extracellular matrix. Molecular alterations of the extracellular matrix in the tumor microenv ... Full text Link to item Cite

PITK, a PP1 targeting subunit that modulates the phosphorylation of the transcriptional regulator hnRNP K.

Journal article Cell Signal · October 2006 Featured Publication Protein phosphatase-1 (PP1), through interactions with substrate targeting subunits, plays critical roles in the regulation of numerous cellular processes. Herein, we describe a newly identified regulatory subunit (PITK; Phosphatase Interactor Targeting K ... Full text Link to item Cite

A phosphatase controls the fate of receptor-regulated Smads.

Journal article Cell · June 2, 2006 Featured Publication In this issue of Cell, Lin et al. (2006) answer one of the long-standing questions in the TGFbeta field by identifying a phosphatase, PPM1A, that directly dephosphorylates Smad2 and Smad3 to limit their activation. ... Full text Link to item Cite

Synchronous endometrial and ovarian tumors: metastatic disease or independent primaries?

Journal article Hum Pathol · June 2005 Featured Publication Full text Link to item Cite

Ubiquitin-mediated degradation a mechanism for fine-tuning TGF-beta signaling.

Journal article Cell · April 8, 2005 Featured Publication Effects of the cytokine TGF-beta can be dampened by E3 ubiquitin ligases that target specific Smads, the TGF-beta signal transducers, for proteolytic destruction. Two papers in this issue of Cell highlight the importance of this mechanism in regulating the ... Full text Link to item Cite

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies.

Journal article Mod Pathol · February 2004 Featured Publication We have observed an increasing number of autopsies on patients with chemotherapy-related complications. One complication is toxic leukoencephalopathy, which is due to a direct toxic effect of chemotherapeutic agents on the central nervous system white matt ... Full text Link to item Cite

Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice.

Journal article Am J Physiol Lung Cell Mol Physiol · March 2002 Featured Publication Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung fibrogenesis. Smad3 was identified in the pathway for transducing TGF-beta signals from the cell membrane to the nucleus. Using mice without Smad3 gene expr ... Full text Link to item Cite

The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis.

Journal article J Bone Miner Res · October 2001 Featured Publication Smad3 is a well-characterized intracellular effector of the transforming growth factor beta (TGF-beta) signaling pathway and was implicated recently in the potentiation of vitamin D receptor (VDR)-mediated signaling. Given that both TGF-beta and vitamin D ... Full text Link to item Cite

RB regulates transcription of the p21/WAF1/CIP1 gene.

Journal article Oncogene · February 22, 2001 Featured Publication We have previously shown that RB plays an important role in the maintenance of the epithelial phenotype. p21 is also involved in several terminal differentiation systems including keratinocytes. We report here that p21 is an RB target gene in epithelial ce ... Full text Link to item Cite

The Smads: transcriptional regulation and mouse models.

Journal article Cytokine Growth Factor Rev · 2000 Featured Publication The field of transforming growth factor-beta (TGF-beta) signaling sees periodic discoveries that revolutionize our thinking, redirect our experiments, and peak our excitement. One of the first such discoveries was less than a decade ago: the molecular clon ... Full text Link to item Cite

Transforming growth factor-beta-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines.

Journal article J Biol Chem · December 3, 1999 Featured Publication We sought to characterize the pathway by which the multifunctional cytokine transforming growth factor-beta (TGF-beta) inhibits the proliferation of normal astrocytes, and we analyzed the alterations in the TGF-beta pathway in human glioma cell lines. Upon ... Full text Link to item Cite

Ras induces p21Cip1/Waf1 cyclin kinase inhibitor transcriptionally through Sp1-binding sites.

Journal article Oncogene · November 4, 1999 Featured Publication p21Cip1/Waf1 cyclin-dependent kinase inhibitor (p21) is inducible by Raf and mitogen-activated protein kinase kinase (MAPKK), but the level of regulation is unknown. We show here by conditional and transient Ras-expression models that Ras induces p21. Indu ... Full text Link to item Cite

Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation.

Journal article Oncogene · May 6, 1999 Featured Publication Addition of nerve growth factor (NGF) to PC12 cells promotes neuronal differentiation while inhibiting cell proliferation. In order to understand how NGF exerts its antimitogenic effect during differentiation, we have studied the mechanism by which this fa ... Full text Link to item Cite

Smads bind directly to the Jun family of AP-1 transcription factors.

Journal article Proc Natl Acad Sci U S A · April 27, 1999 Featured Publication Smad3 and Smad4 are sequence-specific DNA-binding factors that bind to their consensus DNA-binding sites in response to transforming growth factor beta (TGFbeta) and activate transcription. Recent evidence implicates Smad3 and Smad4 in the transcriptional ... Full text Link to item Cite

UV radiation is a transcriptional inducer of p21(Cip1/Waf1) cyclin-kinase inhibitor in a p53-independent manner.

Journal article Exp Cell Res · April 10, 1999 Featured Publication p53 target genes p21(Cip1/Waf1) cyclin-kinase inhibitor (p21 CKI), GADD45, bax, and cyclin G and genes affecting the redox state of the cells are implicated in p53 damage control responses. In order to attribute their functions and dependency of p53 in UV- ... Full text Link to item Cite

Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction.

Journal article Mol Cell Biol · April 1999 Featured Publication The Smads are a family of nine related proteins which function as signaling intermediates for the transforming growth factor beta (TGF-beta) superfamily of ligands. To discern the in vivo functions of one of these Smads, Smad3, we generated mice harboring ... Full text Link to item Cite

Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta.

Journal article Mol Cell Biol · March 1999 Featured Publication Transcriptional regulation by transforming growth factor beta (TGF-beta) is a complex process which is likely to involve cross talk between different DNA responsive elements and transcription factors to achieve maximal promoter activation and specificity. ... Full text Link to item Cite

TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein.

Journal article Mol Biol Cell · December 1998 Featured Publication Smads are intermediate effector proteins that transduce the TGF-beta signal from the plasma membrane to the nucleus, where they participate in transactivation of downstream target genes. We have shown previously that coactivators p300/CREB-binding protein ... Full text Link to item Cite

Molecular mechanisms of transforming growth factor-beta signaling.

Journal article Endocr Rev · June 1998 Featured Publication Full text Link to item Cite

Sp1, but not Sp3, functions to mediate promoter activation by TGF-beta through canonical Sp1 binding sites.

Journal article Nucleic Acids Res · May 15, 1998 Featured Publication Transforming growth factor beta (TGF-beta) causes growth arrest at the G1 phase of the cell cycle in most cell types. Both the cyclin dependent kinase inhibitor p15(INK4B) and p21(Cip1/WAF1) genes have been found to be induced by TGF-beta in human keratino ... Full text Link to item Cite

Tumor suppressor Smad4 is a transforming growth factor beta-inducible DNA binding protein.

Journal article Mol Cell Biol · December 1997 Featured Publication Members of the Smad family of proteins are thought to play important roles in transforming growth factor beta (TGF-beta)-mediated signal transduction. In response to TGF-beta, specific Smads become inducibly phosphorylated, form heteromers with Smad4, and ... Full text Link to item Cite

The viral oncoprotein E1A blocks transforming growth factor beta-mediated induction of p21/WAF1/Cip1 and p15/INK4B.

Journal article Mol Cell Biol · April 1997 Featured Publication The adenovirus early gene product E1A is a potent stimulator of cellular proliferation, which when overexpressed can overcome the growth-inhibitory effects of the polypeptide hormone transforming growth factor beta (TGF-beta). The ability of TGF-beta to ar ... Full text Link to item Cite

Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter.

Journal article J Biol Chem · December 1, 1995 Featured Publication The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors that inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-b ... Full text Link to item Cite

Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism.

Journal article Proc Natl Acad Sci U S A · June 6, 1995 Featured Publication The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors which inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF- ... Full text Link to item Cite

Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression.

Journal article Proc Natl Acad Sci U S A · January 17, 1995 Featured Publication Inhibition of cell growth by type beta transforming growth factor (TGF-beta) occurs in mid-G1 and is associated with decreased G1 cyclin-dependent kinase activity and maintenance of the retinoblastoma tumor suppressor protein Rb in an underphosphorylated, ... Full text Link to item Cite