Killam Seminar Series: Exploring the epigenome to decode microglial inflammatory functions

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David Gosselin

Associate Professor, Molecular Medicine, Université de Laval, Canada

Host: Alyson Fournier

Abstract: Microglia are the macrophages of the brain and participate to its development, homeostasis, and defense against pathogens and injuries. Notably, genetic evidence suggests that they are critically involved in neurodegenerative diseases, including Alzheimer’s disease. However, our knowledge of the molecular processes that regulate these cells and their functions in the brain remains largely incomplete.

Over the past few years, we have concentrated our efforts studying how gene regulation is achieved in microglia, in an effort to better understand how their functions are achieved. In particular, we provided evidence that signaling factors present in the brain act through the epigemome of microglia to promote their cellular identity. Furthermore, our recent work identified the dominant signaling transcriptional regulators that underlie microglial heightened immune activity in pathological conditions, including demyelinating disorders. Notably, our preliminary data suggests that expression of key inflammatory genes may be actively repressed at the chromatin/epigenetic level in microglia in the healthy brain. Thus, their de-repression is likely to be critical to equip microglia with their full array of functions in brain lesions. My talk will provide an overview of these recent findings, and elaborate on the current approaches that we use to gain a better understanding of the epigenomic mechanisms underlying the different cellular functions of microglia in the brain.

Bio: I completed my Ph.D. in physiology-endocrinology at Université Laval in May 2012. My studies, conducted under the supervision of Dr. Serge Rivest, focused on understanding the role of pro-inflammatory cytokine interleukin-1 beta in regulating neuronal activity in various brain-related pathologies. Then, from July 2012 to March 2017, I did a postdoctoral fellowship in epigenomics under the direction of Dr. Christopher Glass at UC San Diego. My studies helped unravel fundamental signaling-epigenomic mechanisms that underlie microglia cell identity. (Gosselin et al., Cell, 2014, Gosselin et al., Science, 2017). Finally, in April 2017, I was recruited at Université Laval, where I lead a research team at the CHU of Quebec-Laval University Research Centre dedicated to the study of the transcriptional mechanisms that underlie microglia functions in health and diseases. Our work is supported by CIHR, MS Society of Canada, Alzheimer’s Society of Canada, and the Scottish Rite Charitable Foundation of Canada.

Supported by the generosity of the Killam Trusts, the MNI's Killam Seminar Series invites outstanding guest speakers whose research is of interest to the scientific community at the MNI and McGill University.