Peter Tontonoz

Position Titles

Professor, Pathology and Laboratory Medicine

Biography

Dr. Tontonoz is Professor and the Francis and Albert Piansky Endowed Chair in Pathology and Laboratory Medicine. He received his B.A. from Wesleyan University and his M.D. and Ph.D. from Harvard Medical School. His Ph.D. thesis was carried out at the Dana-Farber Cancer Institute and his postdoctoral training at the Salk Institute for Biological Studies. He completed his residency training in Pathology at the University of California, San Diego. The focus of his laboratory is the control of gene expression by lipids and the role of nuclear receptors in lipid metabolism. His major research contributions include the delineation of role of PPAR and LXR in adipogenesis and atherosclerosis, and elucidation of mechanisms of crosstalk between metabolism, inflammation and immunity. He has been elected to the American Society of Clinical Investigation and the American Association of Physicians. Dr. Tontonoz is the recipient of the Richard. E. Weitzman and Gerald D. Aurbach Awards from the Endocrine Society, the Jeffrey M. Hoeg Award for Basic Science and Clinical Research from the American Heart Association, and a Bristol Myers-Squibb Freedom to Discover Award in Cardiovascular Disease. He is a past President of American Society for Clinical Investigation. Dr. Tontonoz serves on a number of editorial boards and is a Reviewing Editor for eLife and the Editor in Chief of Molecular and Cellular Biology.

Research Description

Obesity, diabetes and cardiovascular disease are the leading causes of morbidity and mortality in industrialized societies. The common thread that links these disorders is dysregulation of lipid metabolism. The focus of the Tontonoz laboratory is the regulation of the regulation of lipid metabolism and the links between lipids, inflammation and immunity, and metabolic diseases.

Work in our group over the past nineteen years has revealed that the lipid-activated nuclear receptors PPAR and LXR function as coordinators of lipid metabolism and modulators of immunity and inflammation. These transcription factors positively regulate the transcription of a battery of genes directly linked to lipid uptake, efflux and transport, and negatively regulate genes involved in inflammatory responses. Our studies have revealed new mechanisms whereby cholesterol and triglyceride metabolism impact the functions of immune cells. In addition, we have provided in vivo evidence that the LXR and PPAR signaling pathway are important determinant of atherosclerosis, insulin resistance and immune tolerance.

Ongoing work is centered on novel downstream mechanisms by which LXR, PPARs and their target genes regulate lipid and immune homeostasis. We have identified and characterized novel players in the control of lipid homeostasis, including the E3 ligase IDOL, the lncRNAs LeXis and MeXis, the phospholipid remodeling enzyme Lpcat3 and the Aster family of sterol transport proteins. Future studies are expected to provide insight into fundamental regulatory strategies and may identify targets for therapeutic intervention in human metabolic disease.