Samelson-Jones Laboratory

Hemophilia A and hemophilia B are the most common severe bleeding disorders characterized by spontaneous hemorrhages. They are the result of a deficiency in coagulation factor VIII (FVIII) or factor IX (FIX), respectively. During hemostasis, activated FVIII and FIX form the enzyme-complex responsible for the proteolytic activation of factor X (FX), the rate-limiting step of coagulation.

Currently, severe hemophilia A and hemophilia B are treated with prophylactic intravenous administrations of the missing coagulation factor to minimize bleeding. The major complication of this replacement therapy is the development of anti-drug antibodies (ADA), termed inhibitors.

Our laboratory investigates biochemical and immunologic questions aimed at furthering the development of new therapeutics for individuals with hemophilia. We are especially interested in gene transfer to cure hemophilia A and hemophilia B with a focus on adeno associated viral (AAV) vectors.

One approach we have developed to enhance AAV gene therapy is the rational design of new gain-of-function coagulation FVIII and FIX variants with advantageous properties to address limitations of current gene therapy approaches. These studies are guided by ongoing biochemical investigation into the molecular mechanisms of the biological function and regulation of FVIII and FIX. Translational studies include evaluating the safety and efficacy of these new variants working with small and large animal models of hemophilia.

We are also focused on understanding and treating the immunological response to hemophilia therapies. We are developing immuno-proteomic and -genomic platforms to clarify the immunological mechanisms inhibitor development. The goal of this work is to characterize the ADA response to facilitate the development of novel therapeutics for inhibitor patients, including ongoing work to apply chimeric antigen receptor technology to the problem.