Peter Henke, MD, FACS, FAHA   Led by Dr. Peter K. Henke, the Leland Ira Doan Professor of Surgery, the Henke Lab investigates how blood clots in venous thrombosis (VT) resolve over time and how they damage the vein wall as they do. Dr. Henke's work as a vascular surgeon enables our laboratory to ask, and answer, important questions that impact patients' lives and outcomes following VT. Our lab has been funded since 2003 by the National Institutes of Health, the American Venous Forum and other organizations.

Michael Holinstat, PhD  Platelet activation is the final step in maintaining hemostasis following vascular injury. Likewise unregulated platelet activation leads to occlusive thrombus formation, MI, and stroke. My lab focuses on understanding the complex signaling mechanisms that regulate hemostasis and thrombosis. The work in my lab focuses on four primary areas of platelet research spanning from a basic science and drug discovery program to clinical and translational projects including a clinical trial focused on platelet function in type 2 diabetes mellitus, clinical studies on racial disparity in platelet activation and thrombotic risk, identification of novel bioactive lipids in the platelet, and development of first-in-human inhibitors for the prevention of thrombosis and stroke. The models  used in the lab to study these areas of platelet biology include several healthy and patient human cohorts as well as animal proof of principle studies using intravital microscopy, aggregometry, flow cytometry, and other techniques.

Jason Knight, MD  Diabetes mellitus is associated with preclinical macrovascular dysfunction, which predicts the development of atherosclerosis and negative long-term outcomes for diabetic patients. NETosis is a unique form of neutrophil-related cell death whereby massive webs of chromatin and antimicrobial proteins are released into the extracellular space to neutralize infections. While overexuberant NETosis has been associated with accelerated cardiovascular disease in various contexts, its role in diabetes is mostly unstudied. Here, we plan to leverage wire myography, pharmacological approaches, and RNA-seq analysis to determine the role of NETosis in the macrovascular dysfunction of diabetic mice.

James Morrissey, PhD  We are investigating how the blood clotting cascade is regulated, with applications to thrombotic diseases, bleeding disorders, and inflammation. Our lab has recently discovered that polyphosphate (an inorganic polymer of phosphate present in many infectious microorganism and secreted by activated human platelets) is a novel modulator of the blood clotting cascade and may represent the long-sought (patho)physiologic activator of the contact pathway of blood coagulation. Our current research efforts focus primarily on: (1) Understanding, with atomic-scale resolution, how blood clotting proteins interact with membrane surfaces and how these membrane binding events contribute so profoundly to catalysis; and (2) Understanding the mechanisms by which polyphosphate modulates the clotting system in hemostasis, thrombosis and inflammation.

Daniel Myers, DVM, MPH  Venous thrombosis and pulmonary embolism are significant national healthcare concerns. Thrombus and vessel wall damage promotes the up-regulation of adhesion molecules, tissue factor (TF), and inflammatory mediators in vivo. Utilizing animal models, The laboratory have defined the contribution that adhesion molecules, TF, and cytokines play during thrombosis. Recent research suggests that hypoxic and chemical injury to vascular endothelium contributes to the pathogenesis of several cardiovascular diseases. Our research evaluates the effects venous endothelium dysfunction post oxidative injury. Our goal is to define the role of oxidative injury in the pathogenesis of venous thrombosis.

Andrea Obi, MD   Our laboratory, led by Andrea T. Obi, MD(link is external), studies a type of abnormal blood clotting, venous thrombosis, or VT. Our work has led us to look more closely at the role of the immune system and epigenetics in clot formation and breakdown. In fact, we are one of very few laboratories in the world working in this promising area of discovery. Our goal is to take our findings and translate them into new, safer and more effective approaches to treating VT.

Jordan Shavit, MD, PhD  Our laboratory studies the genetics of human blood clotting disorders using zebrafish and mouse models.  Pathologic blood clotting (thrombosis) is responsible for significant patient morbidity and mortality, including deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke .  We have developed models of thrombotic disorders using genome editing nucleases, such as CRISPR.  These models are being used for large-scale zebrafish mutagenesis screens to identify genetic and chemical modifiers of thrombosis. This will be followed by investigation of these modifiers in mouse models and human populations.