BBS Faculty Member - Robert V. Farese, Jr.

Robert V. Farese, Jr.

Department of Molecular Metabolism, HSPH
Department of Cell Biology, HMS
Associate Investigator, Broad Institute of Harvard and MIT

Harvard School of Public Health
665 Huntington Avenue
Building I, Room 207
Boston, MA 02115
Tel: 617-432-6051
Email: robert@hsph.harvard.edu
Visit my lab page here.



Cellular lipid metabolism and homeostasis

Lipids are central to all aspects of life, most prominently as constituents of biological membranes and as major energy reservoirs. Diseases of lipid excess, such as obesity, diabetes, and atherosclerosis, are major global health problems.

The Farese & Walther laboratory studies cellular lipid metabolism and homeostasis. We have two main interests. The first is determining the mechanisms of neutral lipid synthesis and storage in cellular lipid droplets. Neutral lipids, such as sterol esters or triglycerides (TGs), are synthesized by enzymes (such as the DGAT enzymes) in the endoplasmic reticulum (ER) and then are stored in cytosolic organelles called lipid droplets (LDs). Our projects focus on neutral lipid synthesis enzymes (structure and biochemical regulation), LD formation, protein targeting to LDs, and consumption of proteins and lipids on LDs. Our work spans biophysical, biochemical, cell biological, and physiological approaches.

Another area of focus is the cell biology of neurodegeneration. We study the biology of endosome-lysosomal trafficking and function and how disruptions of function lead to neuronal cell dysfunction or death. Projects focus on sphingolipid trafficking and metabolism and on the biology of progranulin, a lysosomal protein whose deficiency leads to frontotemporal dementia (FTD). Our work on FTD is part of the Consortium for FTD Research, a highly collaborative group of laboratories who work together to find treatments for FTD, and the Bluefield Project to Cure FTD (http://www.bluefieldproject.org/).



Last Update: 9/11/2020



Publications

For a complete listing of publications click here.

 


 

Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme. Sui X, Wang K, Gluchowski NL, Elliott SD, Liao M, Walther TC, Farese RV Jr.Nature. 2020 May;581(7808):323-328. doi: 10.1038/s41586-020-2289-6. Epub 2020 May 13 PMID: 32433611

Inhibition of sphingolipid synthesis improves outcomes and survival in GARP mutant wobbler mice, a model of motor neuron degeneration. Petit CS, Lee JJ, Boland S, Swarup S, Christiano R, Lai ZW, Mejhert N, Elliott SD, McFall D, Haque S, Huang EJ, Bronson RT, Harper JW, Farese RV Jr, Walther TC.Proc Natl Acad Sci U S A. 2020 May 12;117(19):10565-10574. doi: 10.1073/pnas.1913956117. Epub 2020 Apr 28.PMID: 32345721
 
Partitioning of MLX-Family Transcription Factors to Lipid Droplets Regulates Metabolic Gene Expression.
Mejhert N, Kuruvilla L, Gabriel KR, Elliott SD, Guie MA, Wang H, Lai ZW, Lane EA, Christiano R, Danial NN, Farese RV Jr, Walther TC.Mol Cell. 2020 Mar 19;77(6):1251-1264.e9. doi: 10.1016/j.molcel.2020.01.014. Epub 2020 Feb 4 PMID: 32023484
 
LDAF1 and Seipin Form a Lipid Droplet Assembly Complex. Chung J, Wu X, Lambert TJ, Lai ZW, Walther TC, Farese RV Jr.Dev Cell. 2019 Dec 2;51(5):551-563.e7. doi: 10.1016/j.devcel.2019.10.006. Epub 2019 Nov 7.PMID: 31708432



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