UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES

The overall goal of our research 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 and 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 more common forms of human obesity. Using large scale automated screening procedures we are further investigating the frequency of mutations in the MC4R gene in large cohorts of obese patients. In parallel we are also searching for obesity causing mutations in additional candidate genes downstream in 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.

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