Biomedical Sciences Graduate Program | University of California, San Francisco

Our laboratory studies the metabolic disturbances that occur during infection. Our major focuses are changes in lipid metabolism and energy balance. Using intact animals, we determine the physiological consequences of the host response to infection and define the cytokine mediators. We then determine the underlying cellular and molecular basis for these changes using both in vivo animal studies and cultured cells. For example, we have identified regulation in the activity of lipid synthesizing enzymes and related proteins that occurs at the level of transcription or post translation. For transcriptional regulation, the response elements and transactivating factors are then defined. Transgenic mouse models are developed to define the roles of key molecules in the host response.

Our laboratory has shown that many of the metabolic changes are part of host defense and not detrimental. We have shown that lipoproteins induced during the host response to infection scavenge toxic bacterial fragments such as LPS and LTA. We have defined the molecules involved in their neutralization.

With regard to energy balance, we determined the mechanisms that induce wasting in AIDS. We also developed specific therapies. We have recently identified a candidate for the molecule that generates fever during the response to infection: Uncoupling Protein 2 (UCP2).