Research Area #1
Intracellular lipid homeostasis
The ability to synthesize (lipogenesis, lipid synthesis), store, and breakdown/release (lipolysis) energy in the form of triacylglycerols is a fundamental process, not just in adipose tissue, but in all tissues. Our research investigates mechanisms that influence the above processes, as well as their physiological relevance. We have contributed to the understanding of key lipid metabolizing enzymes, ATGL/PNPLA2 and adiponutrin/PNPLA3. The former causes Neutral Lipid Storage Disease with Myopathy (NLSDM) in humans. The latter contains a variant (I148M) that is highly associated with non-alcoholic fatty liver disease in humans. Our goal is to understand how fat is safely stored and metabolized in the body, as well as how/why these processes go awry in disease.
Research Area #2
Adipose tissue as an endocrine organ
Adipose-secreted factors (i.e., adipokines, cytokines, lipokines, etc.) are well known to have diverse metabolic effects and also serve as potential therapeutic targets. Numerous potential factors have been identified in preclinical models (i.e., cells, mice); however, their function and physiological relevance remain poorly understood in humans. To address these issues, we evaluate serum and/or tissue endocrine factors in human subjects who are very well-characterized for metabolic phenotypes in the context of different conditions and/or interventions (i.e., diet, physical activity, pharmacotherapy). In this way, we are able to link scientific findings in preclinical models to normal metabolism and disease in humans and vice versa. We are currently participating in a large multi-institutional study to understand the impact of adipose tissue and adipose-secreted factors on muscle, mobility, and aging. Our goal is to identify novel mechanisms by which adipose tissue contributes to disease-relevant phenotypes, and ultimately, to identify targets for therapeutic intervention.