Christian Vaisse, M.D., Ph.D
The overall goal of this laboratory is to identify genetic defects implicated in the onset and progression of multi-factorial metabolic diseases such as obesity and diabetes. Our strategy combines human genetic approaches with molecular biology and animal studies. We are currently concentrating our research on the molecular mechanisms implicated in the hypothalamic effects of the adipocyte secreted, weight regulating hormone, leptin. After describing the first leptin receptor mutation in severely obese humans, we recently found that genetic alterations in the Melanocortin 4 receptor (MC4R), a mediator of the hypothalamic effects of leptin, are responsible for a more common form of human obesity. Using large scale automated screening procedures we now further investigate the frequency of mutations in the MC4R gene in large cohorts of obese patients. In parallel we also search for obesity causing mutations in additional candidate genes downstream the leptin pathway. Finally, both through in vitro and in vivo studies we are aiming to understand how these mutations cause obesity and what the implications are for the treatment of this condition.
Lubrano-Berthelier C., Durand E., Haas K., Dubern B., Shapiro A., Weil J., Ferron C. Froguel P. & Vaisse C (2003) Intracellular Retention Is A Common Characteristic Of Childhood Obesity Associated Mc4r Mutations. Human Molecular Genetics 12:145-153Vaisse C., Clément K., Guy-Grand B., Froguel P. (1998) A Frameshift mutation in human melanocortin-4 receptor results in a dominant form of obesity. Nature Genetics 20:113-114.