个人简介
Professor James Rothman, the Wallace Professor of the Biomedical Sciences at Yale University, is one of the world's most distinguished biochemists and cell biologists. He is Chairman of the Yale School of Medicine’s Department of Cell Biology and is the Director and founder of the Nanobiology Institute on Yale’s new West Campus. Rothman graduated from Yale College (1971) where he studied physics. He received his Ph.D. degree in biological chemistry from Harvard (1976) and was a student at Harvard Medical School from 1971 to 1973. From 1976 to 1978, he completed a fellowship in the Department of Biology at the Massachusetts Institute of Technology. From 1978 to 1988, he was a professor in the Department of Biochemistry at Stanford University. Dr. Rothman was the E.R. Squibb Professor of Molecular Biology at Princeton University (1988-1991). He founded and chaired the Department of Cellular Biochemistry and Biophysics at Memorial Sloan-Kettering Cancer Center (1991-2004), where he held the Paul A. Marks Chair and served as Vice-Chairman of Sloan-Kettering. Prior to coming to Yale in 2008, Dr. Rothman was the Wu Professor of Chemical Biology in the Department of Physiology and Cellular Biophysics, and Director of Columbia University’s Sulzberger Genome Center.
Professor Rothman discovered key molecular machinery responsible for transfer of materials among compartments within cells, providing the conceptual framework for understanding such diverse and important processes as the release of insulin into the blood, communication between nerve cells in the brain, and the entry of viruses to infect cells. Numerous kinds of tiny membrane-enveloped vesicles ferry packets of enclosed cargo. Each type of vesicle must deliver its specialized cargo to the correct destination among the maze of distinct compartments that populate the cytoplasm of a complex animal cell. The delivery process, termed membrane fusion, is fundamental for physiology and medicine, as pathology in this process can cause metabolic, neuropsychiatric and other diseases. Rothman reconstituted vesicle budding and fusion in a cell-free system (1984) and discovered the complex of SNARE proteins (1993) which mediates membrane fusion and affords it specificity. He also uncovered the GTPase-switch mechanism which controls coated vesicle budding in the cell (1991).
Rothman has also contributed to other fields. Together with Gero Miesenbock, he showed how patterns of synaptic activity in neural networks could be recorded optically using encoded synapto-pHlourins (1998). He discovered that hsp70’s are ATPases (1986) and peptide binding proteins (1989), thereby revealing how these molecular chaperones cycle on and off proteins to control their folding/unfolding. On theoretical grounds, he proposed (1981) that the role of the Golgi is to iteratively purify proteins, using its cisternae like plates in a distillation tower, an idea now implicit in all models of Golgi dynamics; and he provided the first evidence of sequential processing and vectorial transport across the stack (1981-1985). Rothman’s current research concerns the biophysics of membrane fusion and its regulation in exocytosis; the dynamics of the Golgi apparatus at super-resolution; and the use of bio-inspired design in nanotechnology.
Dr. Rothman has received numerous awards and honors in recognition of his work on vesicle trafficking and membrane fusion, including the King Faisal International Prize for Science (1996), the Gairdner Foundation International Award (1996), the Lounsbery Award of the National Academy of Sciences (1997), the Heineken Foundation Prize of the Netherlands Academy of Sciences (2000), the Louisa Gross Horwitz prize of Columbia University (2002), the Lasker Basic Science Award (2002), the Kavli Prize in Neuroscience (2010), the Massry Prize (2010) and the EB. Wilson Medal (2010). He is a member of the National Academy of Sciences (1993) and its Institute of Medicine (1995), and a Fellow of the American Academy of Arts and Sciences (1994).
PhD Harvard Medical School (1976)
BA Yale University (1971)
Postdoctoral Fellow Massachusetts Institute of Technology
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Complexin Cross-links perfusion SNAREs into a Zig-Zag
Kümmel, D., Krishnakumar, S.S., Radoff, D.T., Li, F., Giraudo, C.G., Pincet, F., Rothman, J.E., and Reinisch, K.M. 2011. Complexin Cross-links perfusion SNAREs into a Zig-Zag Array. 2011. Nat. Struct. Mol. Biol. 18:927-33.
A Conformational Switch in Complexin is Required for Synaptotagmin to Trigger Synaptic Fusion
Krishnakumar, S.S., Radoff, D.T., Kümmel, D, Giraudo,C.G., Li, F., Khandan, L., Baguley, S.W., Coleman, J., Reinisch, K.M., Pincet, F., and Rothman, J.E. "A Conformational Switch in Complexin is Required for Synaptotagmin to Trigger Synaptic Fusion" Nat. Struct. Mol. Biol. (2011) 18, 933-40.
Complexin Activates and Clamps SNAREpins by a Common Mechanism Involving an Intermediate Energetic State
Li, F., Pincet, F., Perez, E., Giraudo, C.G., Tareste, D., and Rothman, J.E. " Complexin Activates and Clamps SNAREpins by a Common Mechanism Involving an Intermediate Energetic State" Nat. Struct. Mol. Biol. (2011) 18, 941-46.
Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes
Lavieu, G., Orci, L., Shi, L., Geiling, M., Ravazzola, M., Wieland, F., Cosson, P. and Rothman, J. E. “Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes” Proc. Natl. Acad. Sci. (2010) 107, 6876-81.
A fast, single-vesicle fusion assay mimics physiological SNARE requirements
Karatekin, E., Di Giovanni, J., Iborra, C., Coleman, J., O'Shaughnessy, B., Seagar, M. and Rothman, J. E. “A fast, single-vesicle fusion assay mimics physiological SNARE requirements” Proc. Natl. Acad. Sci. (2010) 107, 3517-21
Mostafavi H, Thiyagarajan S, Stratton BS, Karatekin E, Warner JM, Rothman JE, O'Shaughnessy B: Entropic forces drive self-organization and membrane fusion by SNARE proteins. Proc Natl Acad Sci U S A. 2017 May 10; 2017 May 10. PMID: 28490503
Bottanelli F, Kilian N, Ernst AM, Rivera-Molina F, Schroeder LK, Kromann EB, Lessard MD, Erdmann RS, Schepartz A, Baddeley D, Bewersdorf J, Toomre D, Rothman JE: A novel physiological role for ARF1 in the formation of bi-directional tubules from the Golgi. Mol Biol Cell. 2017 Apr 20; 2017 Apr 20. PMID: 28428254
Salpietro V, Lin W, Vedove AD, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS, SYNAPS Study Group., Pitt M, Bello OD, Rothman JE, Basel-Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H: Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome. Ann Neurol. 2017 Apr; 2017 Mar 29. PMID: 28253535
François-Martin C, Rothman JE, Pincet F: Low energy cost for optimal speed and control of membrane fusion. Proc Natl Acad Sci U S A. 2017 Feb 7; 2017 Jan 23. PMID: 28115718
Zhang X, Rebane AA, Ma L, Li F, Jiao J, Qu H, Pincet F, Rothman JE, Zhang Y: Stability, folding dynamics, and long-range conformational transition of the synaptic t-SNARE complex. Proc Natl Acad Sci U S A. 2016 Dec 13; 2016 Nov 28. PMID: 27911771
Li F, Tiwari N, Rothman JE, Pincet F: Kinetic barriers to SNAREpin assembly in the regulation of membrane docking/priming and fusion. Proc Natl Acad Sci U S A. 2016 Sep 20; 2016 Sep 6. PMID: 27601655
Huang F, Sirinakis G, Allgeyer ES, Schroeder LK, Duim WC, Kromann EB, Phan T, Rivera-Molina FE, Myers JR, Irnov I, Lessard M, Zhang Y, Handel MA, Jacobs-Wagner C, Lusk CP, Rothman JE, Toomre D, Booth MJ, Bewersdorf J: Ultra-High Resolution 3D Imaging of Whole Cells. Cell. 2016 Aug 11; 2016 Jul 7. PMID: 27397506
Zanetti MN, Bello OD, Wang J, Coleman J, Cai Y, Sindelar CV, Rothman JE, Krishnakumar SS: Ring-like oligomers of Synaptotagmins and related C2 domain proteins. Elife. 2016 Jul 19; 2016 Jul 19. PMID: 27434670
Pincet F, Adrien V, Yang R, Delacotte J, Rothman JE, Urbach W, Tareste D: FRAP to Characterize Molecular Diffusion and Interaction in Various Membrane Environments. PLoS One. 2016; 2016 Jul 7. PMID: 27387979
Dancourt J, Zheng H, Bottanelli F, Allgeyer ES, Bewersdorf J, Graham M, Liu X, Rothman JE, Lavieu G: Small cargoes pass through synthetically glued Golgi stacks. FEBS Lett. 2016 Jun; 2016 May 31. PMID: 27174538
Yang Y, Wang J, Shigematsu H, Xu W, Shih WM, Rothman JE, Lin C: Self-assembly of size-controlled liposomes on DNA nanotemplates. Nat Chem. 2016 May; 2016 Mar 21. PMID: 27102682
Bello OD, Auclair SM, Rothman JE, Krishnakumar SS: Using ApoE Nanolipoprotein Particles To Analyze SNARE-Induced Fusion Pores. Langmuir. 2016 Mar 29; 2016 Mar 18. PMID: 26972604
Bottanelli F, Kromann EB, Allgeyer ES, Erdmann RS, Wood Baguley S, Sirinakis G, Schepartz A, Baddeley D, Toomre DK, Rothman JE, Bewersdorf J: Two-colour live-cell nanoscale imaging of intracellular targets. Nat Commun. 2016 Mar 4; 2016 Mar 4. PMID: 26940217
Xu W, Wang J, Rothman JE, Pincet F: Accelerating SNARE-Mediated Membrane Fusion by DNA-Lipid Tethers. Angew Chem Int Ed Engl. 2015 Nov 23; 2015 Oct 6. PMID: 26439984
Motta I, Gohlke A, Adrien V, Li F, Gardavot H, Rothman JE, Pincet F: Formation of Giant Unilamellar Proteo-Liposomes by Osmotic Shock. Langmuir. 2015 Jun 30; 2015 Jun 15. PMID: 26038815
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