MICHAUD, Jacques (M.D.)
jacques.michaud@recherche-ste-justine.qc.ca

Career summary, research topics and interests

TITLE

• Associate Professor, Department of Pediatrics, Université de Montréal
• Adjunct Professor, Department of Biochemistry, Université de Montréal

EDUCATION

• Postdoctoral fellow, Department of Embryology, Carnegie Institution of Washington, Baltimore, USA (1997-1999)
• Postdoctoral fellow, Collège de France et Centre National de la Recherche Scientifique, Paris, France (1994-1997)
• Fellow of the Royal College of Physicians of Canada, Medical Genetics, 1998-1994
• Fellow of the Royal College of Physicians of Canada, Pediatrics, 1988-1993
• MD, Faculty of Medicine, Université de Montréal, 1983-1988

RESEARCH INTERESTS

We have developed two research programs that aim at better understanding brain development:

Genetics of Mental Retardation

Although it represents the more frequent severe handicap in children, mental retardation remains largely unexplained. We have hypothesized that de novo point mutation in synaptic genes may explain a large fraction of patients with mental retardation. We have initiated a project that aims at identifying these mutations using a high-throughput sequencing strategy.  Specifically, we are currently sequencing 500 synaptic genes in 190 patients with non-syndromic mental retardation. This unprecedented effort will explore the impact of large-scale sequencing for the exploration of heterogeneous neuro-developmental conditions such as mental retardation.

Development of the hypothalamus

The hypothalamus controls physiological processes, such as feeding, drinking and the maintenance of blood pressure, that are essential for survival. We have developed a research program centered on the hypothesis that disruption of hypothalamic development affects these processes and cause common diseases, such as obesity and high blood pressure. Using genetically-engineered mice, we have identified a cascade of transcription factors that are essential for the development of an important group of hypothalamic neurons. We are currently using different approaches to further dissect this cascade. In parallel, we have shown that the haploinsufficiency of Sim1, which codes for a bHLH-PAS transcription factor that is essential for the development of the hypothalamus, induces severe hyperphagia and obesity in mice. SIM1 haploinsufficiency also causes obesity in humans. We are studying the mechanism by which a decrease of Sim1 disrupts energy balance. These latter observations validate our hypothesis that the study of hypothalamic development can shed light on common diseases that affect homeostasis.   

GRANTS

• Canadian Institutes for Health Research (CIHR)
• Fonds de la Recherche en Santé du Québec

Significant Publications

• Marion JF, Yang C, Caqueret A, Boucher F, Michaud JL, Sim1 and Sim2 are required for correct targeting of mammillary body axons, Development 132:5527-5537, 2005.
• Yang C, Gagnon D, Vachon P, Levy E, Tremblay A, Massie B, Michaud JL, Adenoviral-mediated modulation of Sim1 expression in the paraventricular nucleus affects food intake, Journal of Neuroscience 26:7116-7120, 2006.
• Caqueret A, Boucher F, Michaud JL, Laminar organization of the early developing hypothalamus, Developmental Biology 298:95-106, 2006.
• Piton A*, Michaud JL*, Peng H, Aradhya S, Gauthier J, Mottron L, Champagne N, Hamdan F, Lafrenière RG, Joober R, Fombonne E, Dubé M-P, Haghighi P, Neri C, Marineau C, Drapeau P, Barker PA, Carbonetto S, Rouleau GA (*co-first author), Mutations in the calcium-related gene IL1RAPL1 are associated with autism, Hum Mol Genet 17:3965-3974, 2008.
• Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, Pellerin S, Dobrzeniecka S, Côté M, Perreault-Linck E, Carmant L, D’Anjou G, Fombonne E, Addington AM, Rapoport JL, Delisi LE, Krebs M-O, Mouaffak F, Joober R, Mottron L, Drapeau P, Marineau C, Lafrenière RG, Lacaille J-C, Rouleau GA, Michaud JL, Mutations in SYNGAP1 in non-syndromic mental retardation, New England Journal of Medicine 360:599-605, 2009.
• Hamdan FF, Piton A, Gauthier J, Lortie A, Dubeau F, Dobrzeniecka S, Spiegelman D, Noreau A, Pellerin S, Côté M, Henrion E, Fombonne E, Mottron L, Marineau C, Drapeau P, Lafrenière RG, Lacaille J-C, Rouleau GA, Michaud JL, De novo STXBP1 mutations in mental retardation and non-syndromic epilepsy, Annals of Neurology (in press), 2009.

Awards and distinctions

• FRSQ - Research Scholar, Senior (2007-2010)
• CIHR - Clinical Investigatorship Award (Institute of Genetics) (2007-2009)
• FRSQ - Research Scholar, Junior II (2005-2007)
• CIHR - Clinical-scientist Award (1999-2005)