Photo of Stephen C. Harrison,  PhD

Stephen C. Harrison, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 355-7372
Fax: (617) 730-1967


schadmin@crystal.harvard.edu

Stephen C. Harrison, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Giovanni Armenise - Harvard Professor of Basic Biomedical Science, Biological Chemistry and Molecular Pharmacology, Harvard Medical School
  • Professor, Pediatrics, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

The overall objective of our research is to understand how protein interactions determine subcellular structure. We use direct structural approaches -- principally X-ray crystallography -- to determine the atomic organization of macromolecular complexes. Our present work tackles three groups of questions about molecular localization in cells: (1) how do viruses assemble and get into and out of cells? (2) how do protein assemblies that control transcription integrate diverse signals in switching on or off the expression of specific genes? (3) what is the nature of the molecular machinery for various transport steps in membrane traffic? Specific projects related to cancer include studies of human papillomavirus 16 (HPV16), polyomaviruses, Src and Pak kinases, NFkB, IkB and NFAT. Our Howard Hughes Medical Institutes laboratory is integrated with that of Don Wiley, at tow locations -- the Fairchild Building in the Harvard Department of Molecular and Cellular Biology and the Enders Building at Boston Children's Hospital.

Publications from Harvard Catalyst Profiles

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  • Zahm JA, Harrison SC. A communication hub for phosphoregulation of kinetochore-microtubule attachment. Curr Biol 2024. PubMed
  • Deng S, Cai J, Harrison SC, Zhou H, Hinshaw SM. Recognition of centromere-specific histone Cse4 by the inner kinetochore Okp1-Ame1 complex. EMBO Rep. 2023. PubMed
  • Zahm JA, Jenni S, Harrison SC. Structure of the Ndc80 complex and its interactions at the yeast kinetochore-microtubule interface. Open Biol 2023; 13:220378. PubMed
  • Jenni S, Horwitz JA, Bloyet LM, Whelan SPJ, Harrison SC. Visualizing molecular interactions that determine assembly of a bullet-shaped vesicular stomatitis virus particle. Nat Commun 2022; 13:4802. PubMed
  • Jenni S, Li Z, Wang Y, Bessey T, Salgado EN, Schmidt AG, Greenberg HB, Jiang B, Harrison SC. Rotavirus VP4 Epitope of a Broadly Neutralizing Human Antibody Defined by Its Structure Bound with an Attenuated-Strain Virion. J Virol 2022. PubMed
  • Quan Y, Hinshaw SM, Wang PC, Harrison SC, Zhou H. Ctf3/CENP-I provides a docking site for the desumoylase Ulp2 at the kinetochore. J Cell Biol 2021. PubMed
  • Zahm JA, Stewart MG, Carrier JS, Harrison SC, Miller MP. Structural basis of Stu2 recruitment to yeast kinetochores. Elife 2021. PubMed
  • Herrmann T, Torres R, Salgado EN, Berciu C, Stoddard D, Nicastro D, Jenni S, Harrison SC. Functional refolding of the penetration protein on a non-enveloped virus. Nature 2021; 590:666-670. PubMed
  • Hinshaw SM, Harrison SC. The Structural Basis for Kinetochore Stabilization by Cnn1/CENP-T. Curr Biol 2020; 30:3425-3431.e3. PubMed
  • Tomasek D, Rawson S, Lee J, Wzorek JS, Harrison SC, Li Z, Kahne D. Structure of a nascent membrane protein as it folds on the BAM complex. Nature 2020. PubMed
  • Migl D, Kschonsak M, Arthur CP, Khin Y, Harrison SC, Ciferri C, Dimitrova YN. Cryoelectron Microscopy Structure of a Yeast Centromeric Nucleosome at 2.7 Å Resolution. Structure 2020; 28:363-370.e3. PubMed
  • Fei X, Bell TA, Jenni S, Stinson BM, Baker TA, Harrison SC, Sauer RT. Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate. Elife 2020. PubMed
  • Lee PD, Wei H, Tan D, Harrison SC. Structure of the Centromere Binding Factor 3 Complex from Kluyveromyces lactis. J Mol Biol 2019. PubMed
  • Jenni S, Salgado EN, Herrmann T, Li Z, Grant T, Grigorieff N, Trapani S, Estrozi LF, Harrison SC. In situ Structure of Rotavirus VP1 RNA-Dependent RNA Polymerase. J Mol Biol 2019. PubMed
  • Hinshaw SM, Dates AN, Harrison SC. The structure of the yeast Ctf3 complex. Elife 2019. PubMed
  • Hinshaw SM, Harrison SC. The structure of the Ctf19c/CCAN from budding yeast. Elife 2019. PubMed
  • Chao LH, Jang J, Johnson A, Nguyen A, Gray NS, Yang PL, Harrison SC. How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion. Elife 2018. PubMed
  • Jenni S, Harrison SC. Structure of the DASH/Dam1 complex shows its role at the yeast kinetochore-microtubule interface. Science 2018; 360:552-558. PubMed
  • Jenni S, Dimitrova YN, Valverde R, Hinshaw SM, Harrison SC. Molecular Structures of Yeast Kinetochore Subcomplexes and Their Roles in Chromosome Segregation. Cold Spring Harb Symp Quant Biol 2017. PubMed
  • Hinshaw SM, Harrison SC. Kinetochore Function from the Bottom Up. Trends Cell Biol 2017. PubMed
  • Hinshaw SM, Makrantoni V, Harrison SC, Marston AL. The Kinetochore Receptor for the Cohesin Loading Complex. Cell 2017; 171:72-84.e13. PubMed
  • Harrison SC. Protein tentacles. J Struct Biol 2017. PubMed
  • Kim IS, Jenni S, Stanifer ML, Roth E, Whelan SP, van Oijen AM, Harrison SC. Mechanism of membrane fusion induced by vesicular stomatitis virus G protein. Proc Natl Acad Sci U S A 2017; 114:E28-E36. PubMed
  • Valverde R, Ingram J, Harrison SC. Conserved Tetramer Junction in the Kinetochore Ndc80 Complex. Cell Rep 2016; 17:1915-1922. PubMed
  • Petrovic A, Keller J, Liu Y, Overlack K, John J, Dimitrova YN, Jenni S, van Gerwen S, Stege P, Wohlgemuth S, Rombaut P, Herzog F, Harrison SC, Vetter IR, Musacchio A. Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores. Cell 2016; 167:1028-1040.e15. PubMed
  • Dimitrova YN, Jenni S, Valverde R, Khin Y, Harrison SC. Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly. Cell 2016; 167:1014-1027.e12. PubMed
  • Kuraoka M, Schmidt AG, Nojima T, Feng F, Watanabe A, Kitamura D, Harrison SC, Kepler TB, Kelsoe G. Complex Antigens Drive Permissive Clonal Selection in Germinal Centers. Immunity 2016; 44:542-52. PubMed
  • Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Christopher Fromme J, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P. Data publication with the structural biology data grid supports live analysis. Nat Commun 2016; 7:10882. PubMed
  • Wang Q, Vogan EM, Nocka LM, Rosen CE, Zorn JA, Harrison SC, Kuriyan J. Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate. Elife 2015. PubMed
  • Kirchhausen T, Owen D, Harrison SC. Molecular structure, function, and dynamics of clathrin-mediated membrane traffic. Cold Spring Harb Perspect Biol 2014; 6:a016725. PubMed
  • Hinshaw SM, Harrison SC. An Iml3-Chl4 heterodimer links the core centromere to factors required for accurate chromosome segregation. Cell Rep 2013; 5:29-36. PubMed
  • Corbett KD, Harrison SC. Molecular architecture of the yeast monopolin complex. Cell Rep 2012; 1:583-9. PubMed
  • Böcking T, Aguet F, Harrison SC, Kirchhausen T. Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating. Nat Struct Mol Biol 2011; 18:295-301. PubMed
  • Schmidt AG, Yang PL, Harrison SC. Peptide Inhibitors of Flavivirus Entry Derived from the E-protein Stem. J Virol 2010; 84:12549-54. PubMed
  • Harrison SC, Brugge JS. Mechanistic biology in the next quarter century. Mol Biol Cell 2010; 21:3799-800. PubMed
  • Yu A, Xing Y, Harrison SC, Kirchhausen T. Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling. Structure 2010; 18:1311-20. PubMed
  • Guan R, Han D, Harrison SC, Kirchhausen T. Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding. Structure 2010; 18:1191-8. PubMed
  • Harrison SC. Virology. Looking inside adenovirus. Science 2010; 329:1026-7. PubMed
  • Harrison SC, Kirchhausen T. Structural biology: Conservation in vesicle coats. Nature 2010; 466:1048-9. PubMed
  • Corbett KD, Yip CK, Ee LS, Walz T, Amon A, Harrison SC. The monopolin complex crosslinks kinetochore components to regulate chromosome-microtubule attachments. Cell 2010; 142:556-67. PubMed
  • Al-Bassam J, Kim H, Brouhard G, van Oijen A, Harrison SC, Chang F. CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule. Dev Cell 2010; 19:245-58. PubMed
  • Floyd DL, Harrison SC, van Oijen AM. Analysis of kinetic intermediates in single-particle dwell-time distributions. Biophys J 2010; 99:360-6. PubMed
  • Xing Y, Böcking T, Wolf M, Grigorieff N, Kirchhausen T, Harrison SC. Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly. EMBO J 2010; 29:655-65. PubMed
  • Hite RK, Gonen T, Harrison SC, Walz T. Interactions of lipids with aquaporin-0 and other membrane proteins. Pflugers Arch 2008; 456:651-61. PubMed
  • Ivanovic T, Agosto MA, Zhang L, Chandran K, Harrison SC, Nibert ML. Peptides released from reovirus outer capsid form membrane pores that recruit virus particles. EMBO J 2008; 27:1289-98. PubMed
  • Zhang X, Settembre E, Xu C, Dormitzer PR, Bellamy R, Harrison SC, Grigorieff N. Near-atomic resolution using electron cryomicroscopy and single-particle reconstruction. Proc Natl Acad Sci U S A 2008; 105:1867-72. PubMed
  • Brouhard GJ, Stear JH, Noetzel TL, Al-Bassam J, Kinoshita K, Harrison SC, Howard J, Hyman AA. XMAP215 is a processive microtubule polymerase. Cell 2008; 132:79-88. PubMed
  • Harrison SC. Three-dimensional intricacies in protein-DNA recognition and transcriptional control. Nat Struct Mol Biol 2007; 14:1118-9. PubMed
  • Harrison SC. Comments on the NIGMS PSI. Structure 2007; 15:1344-6. PubMed
  • Bellizzi JJ 3rd, Sorger PK, Harrison SC. Crystal structure of the yeast inner kinetochore subunit Cep3p. Structure 2007; 15:1422-30. PubMed
  • Kim S, Malinverni JC, Sliz P, Silhavy TJ, Harrison SC, Kahne D. Structure and function of an essential component of the outer membrane protein assembly machine. Science 2007; 317:961-4. PubMed
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