Shawn Burgess, Ph.D.
Shawn Burgess, Ph.D., uses magnetic resonance spectroscopy (MRS), mass spectrometry, and biochemical analyses to study metabolic regulation in the liver and other tissues. His ultimate goal is to understand the intricate machinery, which ranges from gene regulation to complex metabolic pathways, by which the body regulates the synthesis and breakdown of glucose and lipids, and how those pathways malfunction in diabetes and fatty liver disease.
In his MRS and mass spectrometry studies, Dr. Burgess uses 2H- and 13C-labeled tracer molecules such as glucose to understand the control mechanisms for glucose synthesis in the liver. For example, his studies have shed light on the role of a key control enzyme for such glucose synthesis, phosphoenolpyruvate carboxykinase (PEPCK).
His work has also shed light on the function of two major regulatory molecules of lipid metabolism in the liver. One biological switch, peroxisome proliferator-activated receptor alpha (PPAR-alpha), is activated by hormones to mobilize fat as an energy source to generate glucose during starvation. The other major regulator, fibroblast growth factor 21 (FGF21), is one of the hormones that triggers PAR-alpha, to help clear fat from the liver and from fat cells by promoting its breakdown. Understanding the subtle and complex interaction of such regulators will aid progress toward drugs to better treat fatty liver disease and diabetes.
In other studies with rats engineered to mimic the pathology of human diabetes, Dr. Burgess has used tracers and MRS to demonstrate how defects in lipid metabolism in the mitochondria of liver cells compromise the liver's ability to break down fats in response to insulin. Mitochondria are the cell's energy plants, and studying their role in lipid metabolism is important for understanding why diabetes is accompanied by abnormally high levels of fat in the liver. Before Dr. Burgess's finding, it had only been known that such defects existed in skeletal muscle cells. His study showed that drugs to activate PPAR-alpha could induce fat breakdown in the rats' livers, but did not lower blood sugar or glucose production, meaning that such drugs could not be used to fully correct the metabolic defects of diabetes.
Dr. Burgess's basic studies are adding to the understanding of the complex pathways of lipid and glucose metabolism and how subtle defects in those pathways can lead to the pathology of diabetes and insulin resistance. He is also deciphering insulin's multifaceted role in regulating glucose and fat metabolism in the body.
In addition to his basic metabolic studies, Dr. Burgess is also collaborating with clinicians to study people with diabetes and insulin resistance, to improve understanding of the disease process and improve treatments.
His clinical studies also include exploring the effects of diet on carbohydrate and fat metabolism in the liver. His studies with colleagues, for example, have revealed that a low-carbohydrate diet dramatically reduces fat content in the liver. Such studies aim at improving the use of diets to control weight and treat such disorders as fatty liver disease.
For publication information please view Dr. Burgess's faculty profile.