Karl C. Desch
A5018179300- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Complement system in diseases
- Blood groups and transfusion
- Genetic Associations and Epidemiology
- Venous Thromboembolism Diagnosis and Management
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hemophilia Treatment and Research
- Blood properties and coagulation
- Erythrocyte Function and Pathophysiology
- Metabolism and Genetic Disorders
- Protease and Inhibitor Mechanisms
- Renal Diseases and Glomerulopathies
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- Diabetes and associated disorders
- Lipid metabolism and disorders
- Atherosclerosis and Cardiovascular Diseases
- Renin-Angiotensin System Studies
- Genomics and Rare Diseases
- Lipoproteins and Cardiovascular Health
- Glycosylation and Glycoproteins Research
- Ethics in Clinical Research
- BRCA gene mutations in cancer
University of Michigan
2016-2025
C. S. Mott Children's Hospital
2015-2024
Michigan United
2015-2023
Orthopaedic University Hospital Friedrichsheim
2020
Ann Arbor VA Medical Center
2019
Center for Non-Communicable Diseases
2017
Howard Hughes Medical Institute
2016
Thrombosis and Atherosclerosis Research Institute
2013
University of Alberta
2013
Institute Of Perinatology Obstetrics And Gynaecology
2005-2008
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening illness caused by deficiency of the vWF-cleaving protease ADAMTS13. Here we show that ADAMTS13-deficient mice are viable and exhibit normal survival, although vWF-mediated platelet-endothelial interactions significantly prolonged. Introduction genetic background CASA/Rk (a mouse strain with elevated plasma vWF) resulted in appearance spontaneous thrombocytopenia subset decreased survival. Challenge these shigatoxin (derived from...
BackgroundMulti‐phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading discovery novel loci. This is first study date comprehensively analyze shared genetic effects within different hemostatic and between these their disease outcomes.ObjectivesTo discover associations by combining summary data traits events.MethodsSummary statistics from genome wide‐association studies (GWAS) seven (factor VII [FVII],...
Neonatal encephalopathy (NE) is characterized by an abnormal level of consciousness with or without seizures in the neonatal period. It affects 1-6/1,000 live term newborns. We applied genome sequencing (GS) newborns NE to investigate underlying genetic causes. enrolled according inclusion/exclusion criteria during their Intensive Care admission. performed GS trio and bioinformatic tools. developed pipelines for manual filters. silico prediction tools, protein 3D modeling, functional...
Interactions between predators and prey are often characterized by strong selection that shapes extreme physiological adaptations for survival in hostile environments. Venom resistance large-bodied South American opossums (Clade Didelphini) provides a striking example as they well known to upon snakes have extremely toxic snake venom. While is this group of opossums, relatively little about the venom remaining diverse speciose members Didelphidae (small-bodied opossums) inhabit same regions...
ABSTRACTErythropoietin (EPO) stimulates erythroid differentiation and maturation. Though the transcriptional regulation of EPO has been well studied, molecular determinants secretion remain unknown. Here, we generated a HEK293T reporter cell line that provides quantifiable selectable readout intracellular levels performed genome-scale CRISPR screen identified SURF4 as an important mediator secretion. Targeting with multiple independent single guide RNAs (sgRNAs) resulted in accumulation...
Significance Here we report a method to rapidly examine the effect of nearly all possible single amino acid substitutions within substrate fragment coagulation protein von Willebrand factor (VWF) on efficiency cleavage by its cognate protease, ADAMTS13. A phage display library was generated containing ∼3.5 × 10 7 independent clones and uncleaved phages collected at multiple reaction time points after with Analysis these high-throughput sequencing facilitated simultaneous calculations k cat /...
The metalloprotease ADAMTS13 cleaves von Willebrand factor (VWF) in circulating blood, limiting the size of VWF multimers and regulating activity. Abnormal regulation contributes to bleeding thrombotic disorders. levels plasma are highly variable among healthy individuals, although heritability genetic determinants this variation unclear. We performed genome-wide association studies concentrations 3244 individuals from 2 independent cohorts individuals. was between 59.1% (all individuals)...
Objective- Leukocyte flux contributes to thrombus formation in deep veins under pathological conditions, but mechanisms that inhibit venous thrombosis are incompletely understood. Ectonucleotide di(tri)phosphohydrolase 1 ( ENTPD1 or Cd39), an ectoenzyme catabolizes extracellular adenine nucleotides, is embedded on the surface of endothelial cells and leukocytes. We hypothesized stasis CD39 regulates inflammation at vein:blood interface a murine model vein thrombosis. Approach Results-...
Background: The signed informed consent document certifies that the process of has taken place and provides research participants with comprehensive information about their role in study. Despite efforts to optimize document, only limited data are available actual use documents by biomedical research. Objective: To examine online a minimal-risk genetic Design: Prospective sibling cohort enrolled as part study hematologic common human traits. Setting: University Michigan Campus, Ann Arbor,...
Abstract Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal mechanism underlying PROCR locus, lower coronary artery disease (CAD) but higher venous thromboembolism (VTE) risk. identify -p.Ser219Gly as likely causal variant at locus and protein C a factor. Using analyses, recall-by-genotype in vitro experimentation, we demonstrate that...
Fabry disease results from loss of activity the lysosomal enzyme α-galactosidase A (GLA), leading to accumulation globoseries glycosphingolipids in vascular endothelial cells. Thrombosis and stroke are life-threatening complications disease; however, mechanism vasculopathy remains unclear. We explored relationship between GLA deficiency cell von Willebrand factor (VWF) secretion vivo vitro models disease. Plasma VWF was significantly higher at two months increased with age Gla-null compared...
The interaction of protein C (PC) with the endothelial PC receptor (EPCR) enhances activated generation. We performed targeted gene sequencing (PROC) and EPCR genes (PROCR) in patients unprovoked venous thromboembolism (VTE) to determine whether mutations that impair PC-EPCR interactions are associated an increased risk VTE.We sequenced exon 3 PROC exons 2 PROCR (the encode protein-protein binding domains EPCR) 653 VTE 627 healthy controls. Five single nucleotide variants, each individual...