Associate Professor of Genetics and Complex Diseases
The metabolic syndrome (or syndrome X), which includes hyperlipidemia, insulin resistance, hypertension and atherosclerosis, is becoming an epidemic due to the increased incidence of obesity in the population. It is estimated that these diseases affect about a quarter of Americans. Increased consumption of the so-called “western-style” diet that is high in fat and carbohydrates undoubtedly plays a causal role in the development of these disorders. To date, however, the molecular link between diets high in fat and the conditions they cause remains elusive.
In the past decade, several nuclear lipid receptors have been identified that serve as sensors for dietary lipids and regulate transcriptional programs important for metabolic homeostasis of the body. More importantly, since the activities of these receptors can be modulated by small molecules, they have become targets for current and prospective drug therapies for components of the metabolic syndrome. The main interest of this laboratory is to study the regulatory mechanisms by these lipid receptors, particularly the peroxisome proliferator-activated receptor (PPAR) subfamily, and to explore the therapeutic value of these lipid sensors in treating metabolic diseases.
The three PPARs, alpha, beta/delta and gamma, are activated by dietary fatty acids and exhibit tissue-specific functions in lipid catabolism as well as storage. We will focus on the activities of the PPARs in metabolically active sites including liver, adipose tissue, muscle and macrophages at the vessel wall. Genetic, pharmacologic and metabolic approaches will be utilized to delineate the molecular mechanisms of how these receptors regulate lipid homeostasis and inflammation, two key components affecting the progression of metabolic diseases. The ultimate goal is to translate the nuclear transcriptional events to physiological and/or pathological outcomes, which may identify molecular targets for drug development.
Ph.D., 1999, University of Minnesota
Photo: Kent Dayton/Harvard Chan School