Lymphoproliferative Angiogenesis and Anti-angiogenic Therapy
My long term research goal is to develop a translational research program in lymphoproliferative diseases, with particular interest in studying the cellular and molecular mechanisms of lymphoproliferative angiogenesis, and development of novel anti-angiogenic therapeutics in both pre-clinical and clinical trial settings. The potential importance of lymphoproliferative angiogenesis arises from the association of disease progression with increased angiogenic activity. We have shown that the vascular composition of human lymphoproliferative subtypes reflects differential recruitment and assembly of either hemangiogenic myelomonocytic cells or mesenchymal smooth muscle cells. We are currently investigating the mechanisms leading to the recruitment and assembly of these peri-vascular accessory cells. In collaboration with Dr. Katherine A. Hajjar, Chairman of the Department of Cell and Developmental Biology at Weill Cornell, we are in the process of studying the potential mechanism of action of a cell surface fibrinolytic receptor, annexin 2, in directing lymphoproliferative neovascular formation in experimental lymphoma models as well as human patients. In parallel, we are actively involved in the development of novel therapeutics targeting tumor angiogenesis in lymphoma patients in the clinical trial setting. Currently, we have two phase II trials opening at Weill Cornell which evaluate anti-angiogenic agents in mantle cell lymphoma (MCL), a subtype of non-Hodgkin's lymphoma (NHL). One combines metronomic oral chemo-regimen PEPC (prednisone, etoposide, procarbazine and cyclophosphamide) with thalidomide and rituximab for patients with relapsed disease. The other combines a monoclonal antibody against VEGF-A, bevacizumab, with standard CHOP-rituximab chemo-immunotherapy for patients with newly diagnosed and untreated mantle cell lymphoma. New agents and their combination with standard treatment are expected to be evaluated in MCL and other NHL subtypes to improve clinical outcome.