Robert V. Farese Jr., MD

Senior Investigator

Phone: (415) 734-2713
Fax: (415) 355-0960
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Professor, Medicine and Biochemistry & Biophysics, University of California, San Francisco

Administrative Assistant

Daryl Jones
(415) 734-2713
djones@gladstone.ucsf.edu

More about Dr. Farese

Dr. Farese’s research focuses on the complex process by which fat molecules are synthesized and stored in cells—investigations that can lead to solutions for obesity and its related conditions, such as heart disease and type 2 diabetes. As a leader of the UCSF-based Consortium for Frontotemporal Dementia (FTD), he also investigates the basic biology of FTD, a common cause of dementia in people under the age of 65.

For his work on metabolism, Dr. Farese won the 2005 “Freedom to Discover Award” from Bristol-Myers Squibb. Dr. Farese has received many other honors, including election to the honorary societies of American Society for Clinical Investigation and Association of American Physicians. He is also a member of the American Heart Association, American Diabetes Association and American Society for Cell Biology.

Dr. Farese earned a bachelor’s degree in chemistry from the University 
of Florida. He completed his medical training at Vanderbilt University and 
his residency and chief residency in internal medicine at the University of Colorado Affiliated Hospitals. He trained in endocrinology at UCSF and was a Postdoctoral Fellow at Gladstone from 1990 to 1992.

 

More scientific details, please

Other Professional Titles

Professor, Medicine and Biochemistry & Biophysics, University of California, San Francisco

Administrative Assistant

Daryl Jones
(415) 734-2713
djones@gladstone.ucsf.edu

Areas of Investigation

Our laboratory studies the mechanisms for how cells synthesize, store, and utilize lipids. Our studies range from the basic biology of DGATs and other enzymes involved in the synthesis of triaglycerols (TGs) to genetic models aimed at discovering genes that govern the formation of cytosolic lipid droplets (LDs), where metabolic energy is stored as TGs and other nonpolar lipids. Our model systems include yeast, mammalian cells, mice, and human induced pluripotent stem (iPS) cells. Our discoveries of basic mechanisms from in vitro and cellular studies are tested in whole organisms for their applications to physiology and disease. Excessive accumulation of lipids in LDs of tissues underlies the pathogenesis of diseases such as obesity, diabetes, fatty liver, and atherosclerosis. Additionally, lipid storage in LDs is a focus of efforts to increase oil yields from crops or microorganisms. Much of our work on cell biology is done in partnership with Dr. Tobias Walther at Yale University.

Our lab also studies progranulin, a secreted protein that is emerging as a key regulator of inflammation with relevance to obesity and diabetes. Our work on progranulin also has direct relevance to frontotemporal dementia (FTD), a common cause of dementia in people under age 65 that can be caused by progranulin mutations.  

Current Lab Focus

  • How are the lipid synthesis enzymes, such as DGATs, regulated?
  • How is lipid synthesis molecularly coupled to lipid-droplet formation?
  • How are proteins targeted to lipid droplets?
  • What is the connection between lipid synthesis pathways and whole-animal energy homeostasis?
  • How does progranulin regulate energy stores? How does progranulin and/or granulin peptides regulate insulin sensitivity?

Joined Gladstone

1990 (postdoctoral fellow)
1993 (faculty)

Why Gladstone?

I came to Gladstone originally for postdoctoral fellowship training, where I studied cholesterol metabolism and mastered the techniques of inducing mutations in mouse embryonic stems cells to generate murine models of physiology and disease.

Key Achievements

  • Used mouse models to elucidate the physiological roles of apolipoprotein B.
  • Cloned genes for many of the enzymes involved in neutral lipid synthesis, most importantly the DGAT enzymes that catalyze triglyceride synthesis and the MGAT enzymes, which mediate intestinal fat absorption.
  • Showed that mice that overexpress DGAT1 in macrophages—thereby increasing the TG storage capacity—are protected against the detrimental consequences of obesity.
  • Identified DGAT1 as a host factor that is required for efficient infection of liver cells by hepatitis C virus (HCV) and that DGAT1 is required for HCV to induce hepatic steatosis (in collaboration with the Ott Laboratory at Gladstone).
  • Identified a key mechanism involved in LD expansion. We found that growing LDs require specific phospholipids to coat their surfaces, and that the synthesis of these lipids is activated at LD surfaces through a fascinating homeostatic mechanism (in collaboration with Dr. Walther’s Laboratory at Yale University).
  • Identified hundreds of novel genes involved in cellular lipid storage and promises more insights releveant to disease and even biofuels (in collaboration with Dr. Walther’s Laboratory at Yale University).
  • Identified several drug targets for obesity, diabetes, and atherosclerosis.

Education

University of Florida (BS), Chemistry (1981)
Vanderbilt University Medical School (MD) (1985)

Affiliations

UCSF Cardiovascular Research Institute
UCSF Liver Center
Hillblom Center for Aging
UCSF Molecular Medicine Training Program
UCSF Medical Scientist Training Program
UCSF Diabetes Center
UCSF Tetrad, Biomedical Sciences and Biophysics Graduate Programs
American Diabetes Association
American Heart Association
American Society for Biochemistry and Molecular Biology
American Society for Cell Biology
Green Pacific Bio, Scientific Advisor

Awards

  • Phi Beta Kappa, Phi Kappa Phi, Golden Key Honor Society, University of Florida (1981)
  • Alpha Omega Alpha Honor Medical Society, Vanderbilt University Medical School (1985)
  • Albert Weinstein Prize in Medicine, Vanderbilt University Medical School (1985)
  • Postdoctoral Research Fellowship Award, Howard Hughes Medical Institute (1991)
  • Irvine H. Page Young Investigator Award (Abstract Finalist), American Heart Association (1995)
  • Established Investigator Award, American Heart Association (1998)
  • Elected to American Society of Clinical Investigation (1999)
  • Elected to Association of American Physicians (2002)
  • Cardiovascular Biology Training Program Distinguished Lecturer, Washington University (2002)
  • Freedom to Discover Unrestricted Metabolic Diseases Research Grant, Bristol-Myers Squibb (2002)
  • Rubenstein Lectureship, Canadian Lipoprotein Conference (2004)
  • University of Colorado, Dept. of Molecular Biology Program, Bodie Lecturer (2011)
  • Keystone Symposium: Lipid Biology and Lipotoxicity; Journal of Lipid Research Lecturer (2012)
Syndicate publications

Featured Publications

Bob Farese, MDHarris C, Herker E, Farese RV, Ott M. Hepatitis C Virus Core Protein Decreases Lipid Droplet Turnover: A MECHANISM FOR CORE-INDUCED STEATOSIS. J Biol Chem. 2011 Dec 9; 286(49):42615-25. View in: PubMed
Bob Farese, MDKrahmer N, Guo Y, Wilfling F, Hilger M, Lingrell S, Heger K, Newman HW, Schmidt-Supprian M, Vance DE, Mann M, Farese RV, Walther TC. Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. Cell Metab. 2011 Oct 5; 14(4):504-15. View in: PubMed