BBS Faculty Member - Robert V. Farese, Jr.

Robert V. Farese, Jr.

Department of Genetics and Complex Diseases, 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: 7/27/2015



Publications

For a complete listing of publications click here.

 


 

Krahmer, N., Guo, Y., Wilfing, F., Hilger, M., Lingrell, S., Heger, K., Newman, H.W., Schmid-Supprian, M., Vance, D. E., Mann, M., Farese, Jr., R.V., Walther, T. C. (2011) Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. Cell Metab. 14:504-15.

Haas, J.T.*, Winter, H.S.*, Lim, E., Kirby, A., Blumenstiel, B., DeFelice, M., Gabriel, S., Branski, D., Grueter, C.A., Toporovski, M.S., Walther, T.C., Daly, M.J., Farese, Jr., R.V. (2012) DGAT1 mutation in a family with a congenital diarrheal disorder.
J. Clin. Invest. 122:4680-4.

Wilfling, F., Wang, H., Haas, J.T., Krahmer, N., Gould, T., Uchida, A., Cheng, J.X., Graham, M., Christiano, R., Fröhlich, F., Liu, X., Buhman, K.K., Coleman, R.A., Bewersdorf, J., Farese, Jr., R.V., Walther, T.C. (2013) Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets.
Dev. Cell. 24:384-99.

Wilfling, F., Thiam, A.R., Olarte, M.J., Wang, J., Beck, R., Gould, T.J. Allgeyer, E.S., Pincet, F., Bewersdorf, J., Farese, R.V., Jr., Walther, T.C. (2014) Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting. Elife, Epub 2014 Feb 4.

* Joint first authors.



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