Myeloma tumor cells can survive even the most aggressive treatment available today, leading to disease relapses. The long-term goal of this project is to develop more effective cytostatic therapies to eradicate myeloma cells. The candidate recently made a novel and exciting discovery that anti-beta2- microglobulin (b2M) monoclonal antibodies (mAbs) had strong apoptotic activity in myeloma cells. She hypothesizes that anti-b2M mAbs may be used as therapeutic agents to treat patients with myeloma. This hypothesis will be tested by the following aims: 1) will examine the mechanisms of anti-b2M mAb-induced apoptosis in myeloma cells to define the role of surface MHC class I and class l-like molecules in these responses, and examine surface proteins binding to, the downstream kinases, and intracellular signaling and apoptosis pathways induced by anti-b2M mAbs;2) will utilize immune effector cells or molecules to enhance the efficacy of anti-b2M mAbs;and 3) will develop strategies to enhance the efficacy of anti-b2M mAbs to induce apoptosis in myeloma cells by combining with novel antimyeloma agents. These novel studies will lead to a better understanding of the role of anti-b2M mAbs in myeloma and may provide another avenue for augmenting currently available therapies for treating MM and potentially other malignancies. The candidate has excellent training and research experience. Her overall career goal is to become an outstanding independent investigator in the field of myeloma translational research. In this proposal, she describes a five-year training program for research career development and proposes to: 1) acquire the necessary additional knowledge and skills in the investigation of myeloma biology and translational research;2) acquire the skills to independently carry out the research program and use the ongoing observational research as a platform for successful applications for federal fundings of myeloma studies. Dr. Qing Yi, a recognized leader in myeloma translational research, will mentor the candidate scientific development. In addition, the environment of M.D. Anderson Cancer Center is a renowned center for research and education training and offers enthusiastic support. RELEVANCE: Based on the previous study, the candidate strongly believes that anti-b2M mAbs are a powerful therapeutic agent to treat myeloma patients in clinic. Moreover, the candidate has outstanding training and formulated research and career development plan. In addition, her mentor and the institute strongly provide enthusiastic support. Thus, the K99/ROO Award will support her transition to the independent investigator position.