Speaker : Dr. Alexandre Orthwein – McGill University, Department of Oncology – CRC Chair Genome Stability and Haematological Malignancies
Title : Influential Role of DNA repair factors in controlling immune development and carcinogenesis
DNA-damaging agents continuously threaten genome integrity and can generate cytotoxic DNA lesions, including DNA double strand breaks (DSBs). These lesions are the necessary intermediates for chromosomal translocations, a hallmark of cancer cells. Paradoxically, B-cells induce DSBs to allow for antibody diversification and an efficient immune defense. These programmed DSBs are preferentially generated in the Immunoglobulin genes to diversify the antibodies that recognize pathogens. Unfortunately, off-target DSBs can arise in proto-oncogenes and tumor suppressor genes leading to rearrangements that fuel B-cell transformation. About 90% of B-cell lymphomas, a subset of acute lymphoblastic leukemia, as well as multiple myeloma display chromosomal translocations involving the Ig genes, placing programmed DSBs as the major etiological source of B-cell cancers. My team is interested to understand the mechanisms underlying DSB signalling and repair as well as the maintenance of genome stability, with a focus on B-cells and their associated malignancies.My laboratory is also interested in deciphering the landscape of factors dictating the response of B-cell pathologies to the standard chemotherapy regimen using systematic approaches including genome-wide CRISPR-mediated screens.