The focus of my research has been on deciphering the complex genetic architecture of human disease traits and modeling complex trait interactions in animal models . As part of the MODEL-AD consortium, my role is to support the efforts in building precise mouse models for late-onset Alzheimer disease by prioritizing human genetic risk variants for the creation of novel mouse models.
2012Recipient of the CHU Sainte-Justine Postdoctoral scholarship of excellence, Montreal. Canada
2016Finalist Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research for the 66th Annual Meeting of the American Society of Human Genetics, Vancouver. Canada
We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies.