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Dr. Munshi received his MD from Maharaja Sayjirao University, India, in 1984. He completed his postgraduate training in Internal Medicine at SSG Hospital and Maharaja Sayjirao University, followed by fellowships at Johns Hopkins Oncology Center and Indiana University Medical Center. In 2001, he joined Dana-Farber Cancer Institute and is currently the Director of Basic and Correlative Science, Jerome Lipper Multiple Myeloma Center.
A major focus of our laboratory research has been identifying novel targets and antigens associated with multiple myeloma, and developing molecular therapeutic strategies including immunotherapy and immuno-gene therapy. In an effort to define the ideal time for vaccination, we discovered both a decreased number and decreased activity of T regulatory cells in myeloma. We identified the cytokines produced in the bone marrow microenvironment that are responsible for this T regulatory cell dysfunction, making these cytokines an important target for improving T cell homeostasis. Moreover, based on our observation of the costimulatory effects of Revlimid (lenalidomide) through the B7-CD28 pathway, we are also developing therapeutic strategies using this agent, to improve immune responses. Based on our in vitro results, we are developing clinical trials to evaluate vaccine strategies in myeloma. In particular, we studied the idiotype as a myeloma-specific antigen and observed specific immune responses. However, because therapeutic strategies directed against a single tumor-associated target may lead to immunological escape, we are identifying additional novel antigens with demonstrated in vivo immunogenicity in myeloma using pre- and post-vaccination patient serum and the Serological Analysis of Recombinant cDNA Expression Library (SEREX). For this work, we have cloned a series of molecules to form a panel of antigens for effective peptide- and protein-based vaccination in myeloma. Another area of research in our laboratory is the evaluation of telomerase as a therapeutic target in myeloma. We identified molecular inhibitors of telomerase that are able to induce telomere shortening and eventual apoptotic cell death. In addition, we developed a unique murine model of human myeloma in which myeloma cells grow exclusively in a human bone implanted in the mice; we use this model to evaluate telomerase inhibitors for a clinical study. The long-term goal of our research efforts is to develop novel therapeutic approaches to myeloma based on bench-side research and then to evaluate patient responses to find better avenues to effective therapy.
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