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Research
I. Transcriptional and Epigenetic Regulation of Hematopoiesis and Immunity by Nuclear Deubiquitinases
Ia. MYSM1 in Hematopoiesis and Hematopoietic Stem Cell Function.
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We have demonstrated that the chromatin binding deubiquitinase MYSM1 is an essential transcriptional regulator of hematopoiesis, hematopoietic stem cell function, and leukocyte development. In recent work, we characterized the cross-talk between MYSM1 and the p53 stress response pathway in the regulation of hematopoiesis, and analyzed the genes regulated by MYSM1 in hematopoietic stem cells. In ongoing work with the support of the Canadian Institutes of Health Research (CIHR), we are analyzing the MYSM1 regulated checkpoints in hematopoiesis and immunity, the molecular mechanisms of MYSM1 activity in these systems, and the pathology of the human MYSM1 deficiency syndrome. The work relies on molecular biology, genetics and bioinformatics, transgenic mouse models, and work with patient samples. With the support of The Leukemia and Lymphoma Society of Canada, we are further exploring the role of MYSM1 in hematologic malignancies.
Ib. Nuclear Deubiquitinases in the Regulation of B Lymphocyte Development and B Cell-Mediated Immune Response.
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With the support of the Natural Sciences and Engineering Research Council of Canada (NSERC), our team is exploring the role of other nuclear deubiquitinases in B cell development and humoral immune response.
II. Hematopoietic Stem Cells in the Physiological Response to Genotoxic and Inflammatory Stress
IIa. Hematopoietic Stem Cells and Inflammatory Stress.
We are exploring hematopoietic stem cell dysfunction in rheumatoid arthritis, a chronic systemic inflammatory disorder that affects one in a hundred adults in Canada. We hypothesize that long-term epigenetic changes in hematopoietic stem cells contribute to the altered immune cell production and disease persistence in this disorder. The research program is conducted in close collaboration with Dr. Ines Colmegna and Dr. David Langlais, and supported by CIHR.
We are also engaged in a collaborative research program, addressing the mechanisms of inflammatory lung disease in systemic autoimmune rheumatic diseases. This research program spans many research teams across McGill University, is supported by the McGill Interdisciplinary Initiative in Infection and Immunity (MI4), and aims to predict disease risk factors and explore new avenues for the development of effective therapies.
IIb. Hematopoietic Stem Cells and Genotoxic Stress.
We are exploring hematopoietic responses to genotoxic stress, and the roles of p53-dependent transcriptional programs and p53-independent mechanisms in this response. The work has implications for the understanding of bone marrow damage in the context of cancer radiotherapy.
For more information on our recent findings, navigate to the Publications page.
