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

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  • Harrison SC. Viral membrane fusion. Virology 2015; 479-480:498-507. 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
  • Bellizzi JJ 3rd, Sorger PK, Harrison SC. Crystal structure of the yeast inner kinetochore subunit Cep3p. Structure 2007; 15:1422-30. PubMed
  • Harrison SC. Comments on the NIGMS PSI. Structure 2007; 15:1344-6. 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
  • Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 2005; 309:1864-8. PubMed
  • Lei M, Robinson MA, Harrison SC. The active conformation of the PAK1 kinase domain. Structure 2005; 13:769-78. PubMed
  • Lacy DB, Wigelsworth DJ, Melnyk RA, Harrison SC, Collier RJ. Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation. Proc Natl Acad Sci U S A 2004; 101:13147-51. PubMed
  • Lei M, Lu W, Meng W, Parrini MC, Eck MJ, Mayer BJ, Harrison SC. Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell 2000; 102:387-97. PubMed
  • Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC. Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell 2000; 5:557-67. PubMed
  • Ferrer M, Kapoor TM, Strassmaier T, Weissenhorn W, Skehel JJ, Oprian D, Schreiber SL, Wiley DC, Harrison SC. Selection of gp41-mediated HIV-1 cell entry inhibitors from biased combinatorial libraries of non-natural binding elements. Nat Struct Biol 1999; 6:953-60. PubMed
  • Bauer PH, Cui C, Liu R, Stehle T, Harrison SC, DeCaprio JA, Benjamin TL. Discrimination between sialic acid-containing receptors and pseudoreceptors regulates polyomavirus spread in the mouse. J Virol 1999; 73:5826-32. PubMed
  • Ferrer M, Harrison SC. Peptide ligands to human immunodeficiency virus type 1 gp120 identified from phage display libraries. J Virol 1999; 73:5795-802. PubMed
  • Musacchio A, Smith CJ, Roseman AM, Harrison SC, Kirchhausen T, Pearse BM. Functional organization of clathrin in coats: combining electron cryomicroscopy and X-ray crystallography. Mol Cell 1999; 3:761-70. PubMed
  • Xu W, Doshi A, Lei M, Eck MJ, Harrison SC. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol Cell 1999; 3:629-38. PubMed
  • Jacobs MD, Harrison SC. Structure of an IkappaBalpha/NF-kappaB complex. Cell 1998; 95:749-58. PubMed
  • Huang H, Chopra R, Verdine GL, Harrison SC. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 1998; 282:1669-75. PubMed
  • ter Haar E, Musacchio A, Harrison SC, Kirchhausen T. Atomic structure of clathrin: a beta propeller terminal domain joins an alpha zigzag linker. Cell 1998; 95:563-73. PubMed
  • Huse M, Eck MJ, Harrison SC. A Zn2+ ion links the cytoplasmic tail of CD4 and the N-terminal region of Lck. J Biol Chem 1998; 273:18729-33. PubMed
  • Berger JM, Fass D, Wang JC, Harrison SC. Structural similarities between topoisomerases that cleave one or both DNA strands. Proc Natl Acad Sci U S A 1998; 95:7876-81. PubMed
  • Chen L, Glover JN, Hogan PG, Rao A, Harrison SC. Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 1998; 392:42-8. PubMed
  • Ferrer M, Godbout KL, Sullivan BJ, Austen DA, Sanderson CT, Kelley KC, Osburne MS, Harrison SC, van Schravendijk MR. Construction and characterization of a radio-iodinatable mutant of recombinant human CD4. J Immunol Methods 1998; 210:215-25. PubMed
  • Stehle T, Harrison SC. High-resolution structure of a polyomavirus VP1-oligosaccharide complex: implications for assembly and receptor binding. EMBO J 1997; 16:5139-48. PubMed
  • Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997; 387:426-30. PubMed
  • Casasnovas JM, Springer TA, Liu JH, Harrison SC, Wang JH. Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface. Nature 1997; 387:312-5. PubMed
  • Musacchio A, Cantley LC, Harrison SC. Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit. Proc Natl Acad Sci U S A 1996; 93:14373-8. PubMed
  • Harrison SC. Peptide-surface association: the case of PDZ and PTB domains. Cell 1996; 86:341-3. PubMed
  • Fass D, Harrison SC, Kim PS. Retrovirus envelope domain at 1.7 angstrom resolution. Nat Struct Biol 1996; 3:465-9. PubMed
  • Stehle T, Yan Y, Benjamin TL, Harrison SC. Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment. Nature 1994; 369:160-3. PubMed
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