Director, NIH Training Program in Hematology
My laboratory studies regulatory mechanisms in blood coagulation, with applications to hemophilia and thrombotic disorders.
The response to vascular injury requires a rapid, powerful response to limit loss of volume and blood elements, but must be limited in time and space to maintain blood flow to uninjured tissues. Understanding the molecular mechanisms that regulate blood coagulation allows manipulation of this balance in bleeding and thrombotic disorders. The intrinsic tenase (factor IXa-factor VIIIa) complex is the rate-limiting step for thrombin generation and subject to multiple regulatory mechanisms.
My laboratory is applying our understanding of these mechanisms to develop modified forms of factor IX(a) that possess enhanced in vivo activity and prolonged half-life for hemophilia B replacement therapy. Likewise, we have developed methods for measuring circulating factor IXa activity in plasma, and are assessing the contribution of this protease in systemic hypercoagulable states. The clinical association between thrombosis and cancer has been long established, but the underlying mechanisms are incompletely understood.
We are evaluating the role of factor IXa in the hypercoagulability associated with ovarian cancer. More broadly, we are examining the role of the hemostatic system in the ovarian cancer microenvironment, with emphasis on potential roles in disease progression.