Carl S. Thummel, Ph.D.
Professor of Human Genetics
15 North 2030 East Room 5200
Eccles Institute of Human Genetics
CAMPUS
(801) 581-2937
Email: carl.thummel@genetics.utah.edu
Dr. Thummel's Lab
Read more about Dr. Thummel
The goal of the research in our lab is to understand how a family of ligand-regulated transcription factors, called nuclear receptors, contribute to human disease risk factors, such as diabetes and obesity. We study these receptors in the context of a simple animal model, the fruit fly Drosophila. Drosophila have been used for over a century to define central aspects of genetics and development. The remarkable lesson from these studies has been that many genes and pathways discovered in the fly carry over through evolution, and can be used to understand key aspects of human biology and causes of human disease. We are currently working on how nuclear receptors sense metabolic compounds, such as fatty acids and cholesterol, and regulate the expression of genes that act in metabolic pathways. In the past year, we have discovered a central role for a nuclear receptor called Hepatic Nuclear Factor 4 (HNF4) in the breakdown of fatty acids for cellular energy. Drosophila HNF4 mutants have low glucose levels, are obese, and die within the first hours of adult life. They abnormally retain fat and are starvation sensitive, consistent with a key role for HNF4 in mobilizing stored fat for energy. The functions of HNF4 in humans remain unclear, and thus our work provides new directions to understand its possible role as a risk for obesity. We are also studying roles for other nuclear receptors in lipid metabolism, cholesterol homeostasis, and carbohydrate metabolism. Taken together our goal is to uncover novel aspects of nuclear receptor signaling that provide insights into how these pathways operate in all higher organisms, including humans.