Ongoing preclinical and clinical trials

Our lab is directly involved in a number of preclinical and clinical trials.

The role of anti-angiogenic factors in the treatment of VEGF-R2 leukemias: Presently, there are several ongoing clinical trials at Weill-Cornell Medical Center and worldwide where the role of VEGF-R2 tyrosine kinase inhibitors, Avastin (anti-VEGF-A), and other anti-angiogenic agents are being studied for the treatment of refractory acute myelogenous leukemias. Our lab is validating the response to anti-angiogenic agents by studying the leukemic cells in vitro and assessing their response to VEGF-A.

Hemangiogenic stem and progenitor cells as surrogate markers for evaluating response to anti-angiogenic agents: Angiogenic factors released by the tumor tissue or ischemic organs induce mobilization of hematopoietic and vascular stem cells to the peripheral circulation. The absolute number of these cells detected during their sojourn in the peripheral circulation correlates closely with the endogenous neo-angiogenic activity. Quantification of the mobilized VEGF-R1and CD133 VEGF-R2 hemangiogenic stem and progenitor cells provides a novel means to assess the angiogenic response to anti-angiogenic agents or chemotherapeutic agents. We are investigating the role of these vascular surrogate markers in patients with colon, breast, and brain tumors.

Acceleration of wound healing by autologous bone marrow transplantation: My group is investigating the role of bone marrow–derived cells in the regulation of wound healing. In an FDA-approved protocol, the marrow of patients with a full-thickness burn (third-degree burn) is harvested and applied to the debrided wounds in conjunction with artificial skin allografts. This study tests whether marrow-derived cells can facilitate revascularization and regeneration of the damaged skin. It also provides the platform for future studies of the potential benefits of preconditioning damaged skin tissue to enhance engraftment and differentiation of marrow-derived cells.

Targeting tumor neovessels with genetically manipulated pro-angiogenic hematopoietic and endothelial progenitor cells: Based on published data and data generated in our laboratory, circulating hemangiogenic progenitors will provide an effective means to target tumor vasculature. It remains to be determined, however, whether such an approach is feasible and effective in a clinical setting. We plan to obtain the peripheral blood of patients with underlying malignancies and isolate pro-angiogenic progenitors. Re-introduction of these tumor-seeking cells armed with anti-angiogenic factors, such as thrombospondin-1, will allow selective targeting and destruction of the tumor neovessels.