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Associate Medical Director
Comprehensive Center for Bleeding Disorders
Associate Professor of Pediatrics
Division of Hematology/Oncology
Medical College of Wisconsin
My lab is interested in the interaction of von Willebrand factor (VWF) with platelets and with collagens in the vascular endothelium. VWF is a coagulation protein that is key in linking platelets (blood clotting cells) to the injured endothelium that lines blood vessels. Therefore, normal VWF requires the ability to interact with platelets (via platelet receptors GPIb and integrin αIIbβ3) and with vascular collagens (including types 1, 3, 4 and 6). In patients with von Willebrand disease (VWD) these interactions may be decreased or absent.
My current R01 grant focuses on type 4 collagen and its role in VWF and platelet interactions. We have generated a mouse model with defective VWF-collagen 4 binding and are currently studying the bleeding symptoms seen in these mice. We have previously shown that defects in collagen 4 binding are not uncommon in patients with types 1 and 2M VWD, and that these may predispose to increased bleeding compared to patients with normal collagen binding. Ongoing work concerns the effect of aberrant collagen binding on VWF function, platelet function, and bleeding phenotype.
As a clinician, I am fascinated by the variability in bleeding experienced by patients with von Willebrand disease (VWD). I also work with Bob Montgomery on the Zimmerman Program for the Molecular and Clinical Biology of VWD. We have enrolled a large number of patients with type 1 von Willebrand disease, and from this group have demonstrated that genetic variants in VWF are most common when the VWF level is below 30%. However, bleeding symptoms are highly variable and not necessarily well correlated with VWF levels. Ongoing research concerns the correlation of genotype and phenotype with bleeding symptoms in patients with VWD, with the ultimate goal of improving diagnosis and treatment for affected patients.
NIH/NHLBI R01: Mechanism of VWF Interactions with Type 4 Collagen; 01/01/2016 - 12/31/2020
*first author a trainee.