James E Rothman, PhD
Sterling Professor of Cell Biology and Professor of ChemistryCards
Additional Titles
Director, Nanobiology Institute
Administrative Support
Rothman Lab
Additional Titles
Director, Nanobiology Institute
Administrative Support
Rothman Lab
Additional Titles
Director, Nanobiology Institute
Administrative Support
Rothman Lab
About
Titles
Sterling Professor of Cell Biology and Professor of Chemistry
Director, Nanobiology Institute
Biography
Professor James Rothman, the Sterling Professor of Cell Biology 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), the EB. Wilson Medal (2010) and the Nobel Prize in Physiology or Medicine (2013). 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).
Appointments
Cell Biology
ProfessorPrimaryChemistry
ProfessorSecondary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Cell Biology
- Cell Biology Research
- Chemistry
- Diabetes Research Center
- Fellowship Training
- Membrane Traffic
- Molecular Cell Biology, Genetics and Development
- Rothman Lab
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
Education & Training
- Postdoctoral Fellow
- Massachusetts Institute of Technology (1978)
- PhD
- Harvard Medical School (1976)
- BA
- Yale University (1971)
Research
Overview
- The biophysical mechanisms of membrane fusion.
- Regulation of vesicle fusion in synaptic transmission.
- Structural and functional organization of the Golgi apparatus.
Medical Subject Headings (MeSH)
- View Lab Website
Rothman Lab
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Frederic Pincet, PhD
Feng Li, PhD
Jeff Coleman, PhD
Shyam Krishnakumar, PhD
Derek Toomre, PhD
Erdem Karatekin, PhD
Membrane Fusion
Golgi Apparatus
Publications
2024
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
Chelban V, Aksnes H, Maroofian R, LaMonica L, Seabra L, Siggervåg A, Devic P, Shamseldin H, Vandrovcova J, Murphy D, Richard A, Quenez O, Bonnevalle A, Zanetti M, Kaiyrzhanov R, Salpietro V, Efthymiou S, Schottlaender L, Morsy H, Scardamaglia A, Tariq A, Pagnamenta A, Pennavaria A, Krogstad L, Bekkelund Å, Caiella A, Glomnes N, Brønstad K, Tury S, Moreno De Luca A, Boland-Auge A, Olaso R, Deleuze J, Anheim M, Cretin B, Vona B, Alajlan F, Abdulwahab F, Battini J, İpek R, Bauer P, Zifarelli G, Gungor S, Kurul S, Lochmuller H, Da’as S, Fakhro K, Gómez-Pascual A, Botía J, Wood N, Horvath R, Ernst A, Rothman J, McEntagart M, Crow Y, Alkuraya F, Nicolas G, Arnesen T, Houlden H. Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications. Nature Communications 2024, 15: 2269. PMID: 38480682, PMCID: PMC10937998, DOI: 10.1038/s41467-024-46354-0.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPrimary familial brain calcificationDisease-causing mechanismsLoss-of-functionReduced surface levelsTransmembrane proteinsNAA60Progressive movement disorderBiochemical explanationAcetylation capacityPhosphate uptakeGenesBrain calcificationVariantsProteinHeterogeneous disorderSLC20A2Neurobiological functionsSurface levelMovement disordersCalcium depositionCellsUnraveling cellular complexity with transient adapters in highly multiplexed super-resolution imaging
Schueder F, Rivera-Molina F, Su M, Marin Z, Kidd P, Rothman J, Toomre D, Bewersdorf J. Unraveling cellular complexity with transient adapters in highly multiplexed super-resolution imaging. Cell 2024, 187: 1769-1784.e18. PMID: 38552613, DOI: 10.1016/j.cell.2024.02.033.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsInter-organelle contactsSuper-resolutionMultiplexed super-resolution microscopyIntricate spatial relationshipsGolgi stacksMammalian cellsCellular functionsSuper-resolution microscopyPrimary ciliaSuper-resolution fluorescence microscopyCellular complexityTransient adaptationFluorescence microscopyDNA-PAINTFluorogenic labelingMolecular targetsSpatial relationshipsImagesThroughput
2023
Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
Bera M, Radhakrishnan A, Coleman J, Sundaram R, Ramakrishnan S, Pincet F, Rothman J. Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2311484120. PMID: 37903271, PMCID: PMC10636311, DOI: 10.1073/pnas.2311484120.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSpecific molecular functionsSynaptic vesicle protein synaptophysinTarget membrane bilayerSensor synaptotagminSNARE proteinsMolecular functionsMembrane proteinsSNAREpinsReceptor vesiclesSingle-molecule measurementsGene knockoutMembrane bilayerLipid bilayersProtein synaptophysinVesiclesDetergent extractsHexamer structureSYPMechanism of actionProteinAssemblyChaperonesSynaptotagminExocytosisBilayers
2011
Complexin activates and clamps SNAREpins by a common mechanism involving an intermediate energetic state
Li F, Pincet F, Perez E, Giraudo CG, Tareste D, Rothman JE. Complexin activates and clamps SNAREpins by a common mechanism involving an intermediate energetic state. Nature Structural & Molecular Biology 2011, 18: 941-946. PMID: 21785413, PMCID: PMC3736826, DOI: 10.1038/nsmb.2102.Peer-Reviewed Original ResearchCitationsMeSH KeywordsA conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion
Krishnakumar SS, Radoff DT, Kümmel D, Giraudo CG, Li F, Khandan L, Baguley SW, Coleman J, Reinisch KM, Pincet F, Rothman JE. A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion. Nature Structural & Molecular Biology 2011, 18: 934-940. PMID: 21785412, PMCID: PMC3668341, DOI: 10.1038/nsmb.2103.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdaptor Proteins, Vesicular TransportAmino Acid SequenceAnimalsBinding SitesCrystallography, X-RayHumansMembrane FusionModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNerve Tissue ProteinsProtein Structure, TertiaryRatsSynaptosomal-Associated Protein 25SynaptotagminsSyntaxin 1Vesicle-Associated Membrane Protein 2Complexin cross-links prefusion SNAREs into a zigzag array
Kümmel D, Krishnakumar SS, Radoff DT, Li F, Giraudo CG, Pincet F, Rothman JE, Reinisch KM. Complexin cross-links prefusion SNAREs into a zigzag array. Nature Structural & Molecular Biology 2011, 18: 927-933. PMID: 21785414, PMCID: PMC3410656, DOI: 10.1038/nsmb.2101.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and Concepts
2010
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, Rothman JE. Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 6876-6881. PMID: 20351264, PMCID: PMC2872465, DOI: 10.1073/pnas.1002536107.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsCortical endoplasmic reticulumMost animal cell typesEndoplasmic reticulumMicrotubule plus-end binding protein EB1Animal cell typesLysine-rich tailRNA interference experimentsEndoplasmic reticulum membraneCoatomer bindingSTIM proteinsMammalian cellsProtein EB1Transmembrane proteinC-terminal peptidePlasma membraneYeast cellsReticulum membraneCell typesPeptide bindsProteinPeptide sequencesIst2ReticulumInterference experimentsDimerizationA fast, single-vesicle fusion assay mimics physiological SNARE requirements
Karatekin E, Di Giovanni J, Iborra C, Coleman J, O'Shaughnessy B, Seagar M, Rothman JE. A fast, single-vesicle fusion assay mimics physiological SNARE requirements. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 3517-3521. PMID: 20133592, PMCID: PMC2840481, DOI: 10.1073/pnas.0914723107.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and Concepts
Academic Achievements & Community Involvement
honor The Nobel Prize in Physiology or Medicine
International AwardThe Nobel Assembly at Karolinska InstitutetDetails10/07/2013Swedenhonor The Kavli Prize for Neuroscience
International AwardThe Kavli FoundationDetails10/15/2010United Stateshonor The E.B. Wilson Medal
National AwardAmerican Society for Cell Biology for ScienceDetails10/12/2010United Stateshonor The Massry Prize
National AwardMeira and Shaul G. Massry FoundationDetails08/11/2010United Stateshonor The Louisa Gross Horwitz Prize
International AwardDetails01/01/2002United States
News
News
- March 28, 2024Source: Cell
FLASH-PAINT enables highly-multiplexed super-resolution microscopy
- September 21, 2020Source: Clear+Vivid with Alan Alda
On discovering 'FedEx trucks' in our cells" - Actor Alan Alda interviews Nobel laureate James Rothman
- August 23, 2019
Royal Society inducts Rothman
- April 17, 2019
Yale’s Rothman Named Fellow of Royal Society
Get In Touch
Contacts
Cell Biology
333 Cedar Street, P.O. Box 208002
New Haven, CT 06520-8002
United States
Administrative Support
Locations
Rothman Laboratory
Lab
Sterling Hall of Medicine, C-Wing
333 Cedar Street, Ste SHM C-434
New Haven, CT 06510
Appointments
203.785.5873