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Regulation of lipid metabolism and its impact on tissue and whole body health

This project has direct relevance to understanding human diseases like atherosclerosis, fatty liver, and diabetes and devising nutritional and pharmacological approaches to mitigate these metabolic diseases. Specifically, we are interested in understanding how lipid metabolism is regulated in different cell types and tissues like liver, intestine, and heart, with a focus on the lipid modifying enzyme, stearoyl-CoA desaturase (SCD). SCD catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids. SCD is a highly regulated enzyme, despite the fact that its products are abundant in our diets. In turn, it plays a critical role in regulating cellular metabolism: animals lacking SCD1 are lean and protected from metabolic disease; and in human cohorts, increased SCD activity is associated with metabolic syndrome. These prior findings have rendered SCD a very attractive target for manipulation of cellular metabolism. Current investigations in our lab are focused on delineating the tissue-specific roles for this highly regulated enzyme and identifying novel roles in understudied tissues. To do this, we use unique transgenic mouse models developed in our lab, as well as primary and immortalized cell lines in culture. We use a combination of cell biological, biochemical, and molecular biology tools to address our questions related to regulation of lipid metabolism and its role in overall health.

Figure title: The regulation of SCD1 and its role in regulating cellular metabolism                   Figure credit: Adapted from Sampath and Ntambi.  Future Lipidology 2008 3:163-73.

Oxidative DNA damage and repair and implications to metabolic health

Oxidative stress, a normal cellular process that is exacerbated by aging or by consumption of sub-par diets, results in damage to DNA pools within the cell. Such oxidative DNA damage is repaired via  the base excision repair (BER) pathway . We study how defects or enhancements in the BER pathway may be utilized to improve metabolic health and function of specific tissues such as muscle and adipose tissue, via modulation of mitochondrial health. By using novel transgenic animals and primary cells, a direct translational goal of these studies is to devise novel means to mitigate age-related losses in tissue function and metabolic fitness.

OGG1 structure.png

Figure title: Protein structure of 8-oxoguanine DNA glycosylase (OGG1), an initiator of BER-mediated DNA repair            Figure credit:

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