Research Topics
Genomes and Genes
| David GinsburgSummaryAffiliation: University of Michigan Country: USA Publications
Research Grants
| Collaborators
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Detail Information
Publications
The molecular biology of von Willebrand diseaseD Ginsburg
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109 9650, USA
Haemophilia 5:19-27. 1999..However, the complex genetic factors determining the clinical severity of type 1 von Willebrand disease, the most common variant, still remain largely unknown and are the subject of current investigation...- Identifying novel genetic determinants of hemostatic balanceD Ginsburg
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan, Life Sciences Institute, Ann Arbor, MI 48109 2216, USA
J Thromb Haemost 3:1561-8. 2005..Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans... 
Genetics and genomics to the clinic: a long road aheadDavid Ginsburg
Howard Hughes Medical Institute, Department of Internal Medicine, and the Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Cell 147:17-9. 2011..This perspective will take brief stock of what genetics/genomics have brought to clinical practice to date and what we might expect for the future...
Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2Bin Zhang
Life Sciences Institute, Department of Internal Medicine, 210 Washtenaw Ave, Ann Arbor, MI 48109-0650, USA
Blood 107:1903-7. 2006....- Reduced thrombin generation increases host susceptibility to group A streptococcal infectionHongmin Sun
Department of Internal Medicine, University of Missouri Columbia, USA
Blood 113:1358-64. 2009.... - LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathwayBin Zhang
Life Sciences Institute, the Departments of Biological Chemistry, Internal Medicine, Human Genetics Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
J Biol Chem 280:25881-6. 2005..MCFD2 may function to specifically recruit factor V and factor VIII to sites of transport vesicle budding within the endoplasmic reticulum lumen... - Modifiers of von Willebrand factor identified by natural variation in inbred strains of miceJordan A Shavit
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA
Blood 114:5368-74. 2009..Mvwf6 displays conservation of synteny with potential VWF modifier loci identified in human pedigrees, suggesting that its ortholog may modify VWF in human populations... - The murine platelet and plasma factor V pools are biosynthetically distinct and sufficient for minimal hemostasisHongmin Sun
Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan, Ann Arbor, 48109, USA
Blood 102:2856-61. 2003..In addition, these findings indicate that the murine platelet and plasma FV pools are biosynthetically distinct, in contrast to a previous report demonstrating a plasma origin for platelet FV in humans... - Selection on cis-regulatory variation at B4galnt2 and its influence on von Willebrand factor in house miceJILL M JOHNSEN
Department of Internal Medicine, University of Michigan, USA
Mol Biol Evol 26:567-78. 2009..Similar mechanisms may account for the variability in VWF levels and high prevalence of VWD in other mammals, including humans... - Spontaneous Irs1 passenger mutation linked to a gene-targeted SerpinB2 alleleRandal J Westrick
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Proc Natl Acad Sci U S A 107:16904-9. 2010..When linked to a targeted allele, such mutations could lead to incorrect assignment of phenotype and may account for a subset of markedly discordant results from experiments independently targeting the same gene... - Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide associationKarl C Desch
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA
Proc Natl Acad Sci U S A 110:588-93. 2013..These results raise the possibility that similar loci could explain a significant portion of the "missing heritability" for other complex genetic traits... - Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in miceHongmin Sun
Department of Internal Medicine, University of Missouri Hospital and Clinics, Columbia, MO 65212, USA
Proc Natl Acad Sci U S A 109:3469-74. 2012..These data suggest that the class of compounds represented by CCG-2979 may be of therapeutic value for the treatment of GAS and potentially other gram-positive infections in humans... - The endothelial-specific regulatory mutation, Mvwf1, is a common mouse founder alleleJILL M JOHNSEN
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 48109 2216, USA
Mamm Genome 19:32-40. 2008..Similar selective pressures could contribute to the high prevalence of von Willebrand disease in humans... - Plasminogen is a critical host pathogenicity factor for group A streptococcal infectionHongmin Sun
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Science 305:1283-6. 2004..In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens... - Atherosclerosis progression in LDL receptor-deficient and apolipoprotein E-deficient mice is independent of genetic alterations in plasminogen activator inhibitor-1H Sjöland
Division of Cardiology, Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109 0644, USA
Arterioscler Thromb Vasc Biol 20:846-52. 2000.... - Enhanced VWF biosynthesis and elevated plasma VWF due to a natural variant in the murine Vwf geneHeidi L Lemmerhirt
Howard Hughes Medical Institute, University of Michigan, 210 Washtenaw, Life Sciences Institute, Rm 5028, Ann Arbor, MI 48109, USA
Blood 108:3061-7. 2006..The identification of a natural Vwf gene variant among inbred mice affecting biosynthesis suggests that similar genetic variation may contribute to the wide range of VWF levels observed in humans... - Fatal hemorrhage in mice lacking gamma-glutamyl carboxylaseAihua Zhu
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA
Blood 109:5270-5. 2007.... - The COPII pathway and hematologic diseaseRami Khoriaty
Department of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA
Blood 120:31-8. 2012..These diseases and their molecular pathogenesis are the focus of this review... - Homozygosity for factor V Leiden leads to enhanced thrombosis and atherosclerosis in miceDaniel T Eitzman
Division of Cardiology, University of Michigan Medical Center, Ann Arbor 48109 0644, USA
Circulation 111:1822-5. 2005..Although the impact of FVL on the development of venous thrombosis is well established, its effect on arterial thrombosis and atherosclerosis is controversial... - Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid arteryD T Eitzman
Divisions of Cardiology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA
Blood 96:4212-5. 2000..Blood. 2000;96:4212-4215).. - Vitronectin inhibits the thrombotic response to arterial injury in miceW P Fay
Departments of Internal Medicine and Human Genetics and the Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA
Blood 93:1825-30. 1999.... - Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in miceD T Eitzman
Cardiovascular Research Center and Division of Molecular Medicine and Human Genetics, Department of Internal Medicine, and the Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 49109 0644, USA
Blood 95:577-80. 2000..01 compared to WT mice). These results suggest that endogenous fibrinolysis and its regulation by PAI-1 and VN have important roles in the development of occlusive vascular thrombosis after vascular injury. (Blood. 2000;95:577-580).. - Vitronectin is not essential for normal mammalian development and fertilityX Zheng
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109 0650, USA
Proc Natl Acad Sci U S A 92:12426-30. 1995..These observations demonstrate that VN is not essential for cell adhesion and migration during normal mouse development and suggest that its role in these processes may partially overlap with other adhesive matrix components... - Hyperlipidemia promotes thrombosis after injury to atherosclerotic vessels in apolipoprotein E-deficient miceD T Eitzman
Cardiovascular Research Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109 0644, USA
Arterioscler Thromb Vasc Biol 20:1831-4. 2000.... - Exocyst function is regulated by effector phosphorylationXiao Wei Chen
Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
Nat Cell Biol 13:580-8. 2011..The exocyst thus serves as a 'gatekeeper' for exocytic vesicles through a circuit of engagement, disengagement and re-engagement with G proteins... - Transgenic overexpression of a stable Plasminogen Activator Inhibitor-1 variantAbigail T Fahim
Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States
Thromb Res 123:785-92. 2009..This study aimed to engineer transgenic overexpression of a stable murine PAI-1 variant to examine the physiologic effects in vivo from delayed transition of PAI-1 to latency... - pak2a mutations cause cerebral hemorrhage in redhead zebrafishDavid A Buchner
Howard Hughes Medical Institute and Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Proc Natl Acad Sci U S A 104:13996-4001. 2007..These data provide in vivo evidence for a critical function of Pak2 in vascular integrity and demonstrate a severe disease phenotype resulting from loss of Pak2 function... - Mvwf, a dominant modifier of murine von Willebrand factor, results from altered lineage-specific expression of a glycosyltransferaseK L Mohlke
Howard Hughes Medical Institute, The University of Michigan, Ann Arbor 48109 0650, USA
Cell 96:111-20. 1999..These findings identify alterations in glycosyltransferase function as a potential general mechanism for the genetic modification of plasma protein levels... - The plasminogen activator inhibitor-2 gene is not required for normal murine development or survivalK M Dougherty
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109 0650, USA
Proc Natl Acad Sci U S A 96:686-91. 1999..Finally, crossing PAI-2 -/- with PAI-1 -/- mice to generate animals deficient in both plasminogen activator inhibitors failed to uncover an overlap in function between these two related proteins... - Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIIIW C Nichols
Department of Internal Medicine, University of Michigan, Ann Arbor 48109 0650, USA
Cell 93:61-70. 1998..These findings suggest that ERGIC-53 may function as a molecular chaperone for the transport from ER to Golgi of a specific subset of secreted proteins, including coagulation factors V and VIII... - Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor VJ Cui
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, USA
Nature 384:66-8. 1996.... - SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretionXiao Wei Chen
Life Sciences Institute, University of Michigan, Ann Arbor, United States
elife 2:e00444. 2013..DOI:http://dx.doi.org/10.7554/eLife.00444.001... - Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifsJohn A Bernat
Department of Human Genetics, Howard Hughes Medical Institute, USA
Hum Mol Genet 15:2098-105. 2006..This motif contains the core element of binding sites from the Ets family of transcription factors. Thus, one or several factors from this family may play a key role in the regulation of endothelial gene expression... - Lethal perinatal thrombosis in mice resulting from the interaction of tissue factor pathway inhibitor deficiency and factor V LeidenDaniel T Eitzman
Division of Cardiology, University of Michigan Medical Center, Ann Arbor, Mich 48109 0644, USA
Circulation 105:2139-42. 2002..Variation in the expression of tissue factor pathway inhibitor (TFPI) has also been proposed as a risk factor for venous thrombosis and has been shown to enhance the prothrombotic effect of FVL in vitro... - Analysis of informed consent document utilization in a minimal-risk genetic studyKarl Desch
University of Michigan, Ann Arbor, USA
Ann Intern Med 155:316-22. 2011..Despite efforts to optimize the informed consent document, only limited data are available about the actual use of consent documents by participants in biomedical research... - Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complexBin Zhang
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109 0650, USA
Nat Genet 34:220-5. 2003..MCFD2 is localized to the ERGIC through a direct, calcium-dependent interaction with LMAN1. These findings suggest that the MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins... - Getting secretory granules ready for prime timeBin Zhang
Howard Hughes Medical Institute and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Cell 115:372-3. 2003..identify mutations in Munc13-4 as a cause of familial hemophagocytic lymphohistiocytosis. Munc13-4 appears to be involved in the priming of cytotoxic granules prior to fusion with the plasma membrane... - What a polyclonal antibody sees in von Willebrand factorFen Lai Tan
Department of Internal Medicine, Life Science Institute, Howard Hughes Medical Institute, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
Thromb Res 121:519-26. 2008..Von Willebrand factor (VWF) plays a critical role in hemostasis by carrying factor VIII (FVIII) and binding to specific ligands on the surface of blood platelets and within the blood vessel wall... - Biosynthetic origin and functional significance of murine platelet factor VTony L Yang
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Blood 102:2851-5. 2003.... - Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disordersB Zhang
Department of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI 48109-0650, USA
J Thromb Haemost 2:1564-72. 2004..The multiple coagulation factor deficiencies provide a notable example of important basic biological insight gained through the study of rare human diseases... - Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (IIe865 to Thr)M C Iannuzzi
Department of Internal Medicine, Howard Hughes Medical Institute, Ann Arbor, MI
Am J Hum Genet 48:757-63. 1991..This substitution is located immediately adjacent to two previously identified type IIA vWD mutations... - von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor geneW C Nichols
Howard Hughes Medical Institute, Ann Arbor, MI
Blood 83:3225-31. 1994..These observations may provide new insights into the molecular basis and variable expressivity of human vWD... - Comparative mapping of distal murine chromosome 11 and human 17q21.3 in a region containing a modifying locus for murine plasma von Willebrand factor levelK L Mohlke
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA
Genomics 54:19-30. 1998..These data may also aid in the localization of other disease loci mapped to this region, including the gene for tricho-dento-osseous syndrome and a murine locus for susceptibility to ozone-induced acute lung injury... - Modifier genes for disorders of thrombosis and hemostasisR J Westrick
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
J Thromb Haemost 7:132-5. 2009.... - Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient miceDavid G Motto
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
J Clin Invest 115:2752-61. 2005..These data suggest that microbe-derived toxins (or possibly other sources of endothelial injury), together with additional genetic susceptibility factors, are required to trigger TTP in the setting of ADAMTS13 deficiency... - Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpuraG G Levy
Howard Hughes Medical Institute, Departments of Internal Medicine and Human Genetics, and Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
Nature 413:488-94. 2001..We show that deficiency of ADAMTS13 is the molecular mechanism responsible for TTP, and suggest that physiologic proteolysis of VWF and/or other ADAMTS13 substrates is required for normal vascular homeostasis... - The structure and function of murine factor V and its inactivation by protein CT L Yang
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109 0650, USA
Blood 91:4593-9. 1998..Thus, the structure and function of FV and its interaction with APC are highly conserved across mammalian species... - Rescue of fatal neonatal hemorrhage in factor V deficient mice by low level transgene expressionT L Yang
Department of Human Genetics, University of Michigan, Ann Arbor, USA
Thromb Haemost 83:70-7. 2000.... - Genetic regulation of plasma von Willebrand factor levels: quantitative trait loci analysis in a mouse modelH L Lemmerhirt
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
J Thromb Haemost 5:329-35. 2007..We have previously mapped two genes contributing to the regulation of plasma VWF levels in mice (Mvwf1 on chromosome 11 and Mvwf2 on chromosome 6)... - Characterization of Leu777Pro and Ile865Thr type IIA von Willebrand disease mutationsS E Lyons
Program in Cellular and Molecular Biology, Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor
Blood 83:1551-7. 1994..An increase in the proportion of high molecular weight multimers observed in type IIA vWD patient plasma, after renal transplantation from a normal donor, suggests that the kidney endothelium may be a major source of plasma vWF... - LMAN1 is a molecular chaperone for the secretion of coagulation factor VIIIM A Cunningham
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0650, USA
J Thromb Haemost 1:2360-7. 2003..These results are interpreted based on the recent determination of the crystal structure of the carbohydrate recognition domain of LMAN1... - Getting at the variable expressivity of von Willebrand diseaseG Levy
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, USA
Thromb Haemost 86:144-8. 2001..This review will focus on the current understanding of the genetic causes for variation in VWF level, and will highlight future directions for getting at the variable expressivity of von Willebrand disease...
Research Grants
- CKIS AND CONTROL OF VASCULAR SMOOTH MUSCLE CELL CYCLEDavid Ginsburg; Fiscal Year: 2001..An understanding of these mechanisms should lend insight into the pathophysiology of vascular diseases, and determine whether enhancement of p21 and p27 expression in arteries may limit excessive vsmc proliferation in these diseases. ..
- 2002 Gordon Research Conference on HemostasisDavid Ginsburg; Fiscal Year: 2002..The extensive interactions and discussion that will occur at this conference will help identify new areas and directions for future research...
- Expression of Myomesin and SLIM1 in Heart FailureFen Lai Tan; Fiscal Year: 2004..abstract_text> ..
- MOLECULAR GENETIC STUDY OF VONWILLEBRAND FACTORDavid Ginsburg; Fiscal Year: 2007..The results of these studies should offer new insight into the biology of endothelial cell function and VWF biosynthesis and may also lead to improved diagnosis and therapy for VWD and thrombophilia. ..