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John P. Manis, M.D. John P. Manis, M.D.

Associate Professor
Department of Pathology
Harvard Medical School
Joint Program in Transfusion Medicine
Children's Hospital Boston

Research Interests

Our lab focuses on the response to and repair of programmed DNA breaks that occur during the development of B lineage cells in the immune system. B cells undergo programmed DNA breaks during a normal immune response in order to generate higher affinity antibodies with specialized functions. Immunoglobulin class switch recombination (CSR) alters the effector function of antibodies without changing the antigen specificity, employing a process that requires DNA double strand breaks. Errors in the repair of programmed double strand breaks required for CSR are thought to result in oncogenic translocations commonly seen in human B cell lymphoma. We seek to elucidate the role of the DNA damage response (DDR) pathway in the development of germinal center B cell lymphoma, focusing on members of the DDR pathway including ATM, 53BP1, and H2AX. The DDR pathway is triggered early after DNA damage and activated during the initial phases of carcinogenesis. By examining the DDR both in normal human B cell populations within a germinal center reaction, and in lymphoma samples, we can gain valuable insights into the alterations that predispose to lymphomagenesis and additionally allow for the development of clinically useful diagnostic and prognostic tools. Our research program has three overall goals, with a central theme of translating basic findings using mouse models to understand and improve treatment of human lymphoma.

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