Tobias Christian Walther
Professor of Cell Biology, Harvard Medical School
Investigator, Howard Hughes Medical Institute
Our research focuses on understanding lipid synthesis and storage, and how these processes are coordinated with energy and membrane generation.
Lipids are central to all aspects of life, most prominently as constituents of biological membranes and as a major energy reservoir. The availability of energy for membrane synthesis, as well as the need for energy expenditure and membrane biogenesis fluctuates. Most cells have thus evolved buffer systems to store lipids and regulatory mechanisms to adapt metabolism to changing needs for lipids. The over-accumulation of lipids and the concomitant overwhelming of homeostatic mechanisms lie at the heart of the current pandemic of metabolic diseases, seen by many as the most pressing global public health problem of the future. We determine how homeostasis is achieved through buffer systems of lipid storage, the regulation of metabolic pathways, and the coordination of lipid metabolism with other cellular and physiological processes. The goal of our work is to provide basic insights into lipid homeostasis, both to define how cells and organisms work and to identify treatments for metabolic diseases. As a general strategy, we combine biophysical, biochemical, structural and physiology approaches with unbiased analytic tools, such as high resolution mass spectrometry based proteomics, lipidomics or genetic screening to answer focused questions.
Prévost, C., Sharp, M.E., Kory, N., Lin, Q., Voth, G.A., Farese R.V. Jr. *, Walther T.C. * Mechanism and determinants of amphipathic helix-containing protein targeting to lipid droplets. Dev Cell. 2018 Jan 8;44(1):73-86.
Inloes JM, Kiosses WB, Wang H, Walther TC, Farese RV Jr, Cravatt BF. Functional contribution of the spastic paraplegia-related triglyceride hydrolase DDHD2 to the formation and content of lipid droplets. Biochemistry. 2017 Dec 26. doi: 10.1021/acs.biochem.7b01028
Walther T.C.†, Chung, J., Farese, R.V. Jr. Lipid Droplet Biogenesis. Annu Rev Cell Dev Biol. 2017 Aug 9. doi: 10.1146/annurev-cellbio-100616-060608.
Chitraju, C., Mejhert, N., Haas, J.T., Diaz-Ramirez, L.G., Grueter, C.A., Imbriglio, J.E., Pinto, S., Koliwad. S.K., Walther, T.C. †, Farese, R.V. Jr. Triglyceride synthesis by DGAT1 protects adipocytes from lipid-induced ER stress during lipolysis. Cell Metab. 2017 Aug 1;26(2):407-418.e3. doi: 10.1016/
Christiano, R., Kolev, N.G., Shi, H., Ullu, E., Walther, T.C., Tschudi, C. The proteome and transcriptome of the infectious metacyclic form of Trypanosoma brucei define quiescent cells primed for mammalian invasion. Mol Microbiol. 2017 Jul 25. doi: 10.1111/
Gluchowski, N.L., Becuwe, M., Walther, T.C†., Farese, R.V. Jr. Lipid droplets and liver disease: from basic biology to clinical implications. Nat Rev Gastroenterol Hepatol. 2017 Apr 21. doi: 10.1038/nrgastro.2017.32.
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