Frances Brodsky, DPhil

Frances Brodsky, DPhil

Professor, Departments of Biopharmaceutical Sciences, Pharmaceutical Chemistry, and Microbiology/Immunology, UCSF

Phone: (415) 476-6406 (voice)
Box 0552, UCSF
San Francisco, CA 94143-0552

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Research Summary

Clathrin is a self-assembling protein that controls the formation of intracellular transport vesicles required for several key membrane traffic pathways. These include receptor-mediated endocytosis and biogenesis of lysosomes and secretory granules. Thus clathrin plays a critical role in cell growth control, antigen presentation, neuronal function and hormone secretion. Malfunction of clathrin pathways is associated with development of cancer, heart disease and neuronal defects. Clathrin-mediated pathways are also subverted by certain viruses and intracellular bacteria to facilitate their infection. A novel isoform of clathrin (CHC22) that is primarily expressed in skeletal muscle, cardiac muscle and fat has been recently characterized by the Brodsky laboratory. Its tissue-specific function is to package the GLUT4 glucose transporter into intracellular vesicles that are released in response to insulin stimulation, leading to clearance of glucose from the bloodstream. This CHC22 clathrin isoform is therefore associated with pathways that are defective in type 2 diabetes. The focus of the Brodsky laboratory since 1982 has been to define the biochemistry, regulation, evolution and physiological function of the clathrin subunits and their isoforms, focusing on their role in disease states, as well as in normal cellular physiology. The laboratory has made significant contributions in these areas over the years and maintains an international reputation for expertise on clathrin structure and function.

There are four current projects in the laboratory. These projects aim to define the comparative functions of the two clathrin heavy chain (CHC) isoforms (CHC17 and CHC22) and the two clathrin light chain isoforms (LCa and LCb). The regulation of CHC17 clathrin function by signaling pathways and the cooperation of CHC17 clathrin with the actin cytoskeleton through clathrin light chain interaction with the actin-binding Hip proteins is being investigated in the context of cell adhesion and migration. Establishing the mechanistic role of CHC22 clathrin in GLUT4 transport and pathways that malfunction in type 2 diabetes is also a major goal for the laboratory.


Harvard University, Massachusetts, B.A., 1976, Biochemistry
Oxford University, England, D. Phil., 1979, Genetics
Harvard University, Massachusetts, Postdoc 1980, Biochemistry
Stanford University, California Postdoc, 1980-82, Structural Biology

Professional Experience

  • 1976-1979
    Graduate Student with Dr. W.F. Bodmer, Genetics Laboratory, Oxford, U.K.
  • 1979-1980
    Postdoctoral Fellow with Dr. J.L. Strominger, Harvard University, Cambridge, MA
  • 1980-1982
    Postdoctoral Fellow with Dr. P. Parham, Stanford University, School of Medicine, Stanford, CA
  • 1982-1986
    Program Manager, Cell Biology, Research and Development Department, Becton Dickinson Immunocytometry Systems
  • 1987-1991
    Assistant Professor of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy; Assistant Adjunct Professor of Microbiology, School of Medicine, University of California, San Francisco.
  • 1991-1994
    Associate Professor of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy; Associate Professor of Microbiology and Immunology, School of Medicine, University of California, San Francisco
  • 1994-Present
    Professor of Biopharmaceutical Sciences and Pharmaceutical Chemistry, School of Pharmacy; Professor of Microbiology and Immunology, School of Medicine, University of California, San Francisco

Honors & Awards

  • 1975
    Dreyfus Fellowship (summer research), Phi Beta Kappa-junior year
  • 1976
    Graduated Summa cum laude in Biochemical Sciences, Harvard
  • 1976-1979
    Marshall Scholarship for study in the United Kingdom
  • 1980-1982
    Damon Runyon-Walter Winchell Fund, Postdoctoral Fellowship
  • 1984-1999
    Member, Editorial Board of Human Immunology
  • 1987
    Pharmaceutical Manufacturers Association Fund Research Starter Grant
  • 1988-1992
    Pew Scholar award
  • 2005
    Boehinger-Ingelheim Lecturer, McGill University
  • 2005-2007
    Honorary Professor, Institute for Molecular Bioscience, University of Queensland
  • 2006-2011
    Member, Searle Scholars Advisory Board
  • 2006
    Margaret Pittman Lecturer, National Institutes of Health
  • 2006
    Visiting fellow, King's College Cambridge

Selected Publications

  1. Goyos A, Guethlein LA, Horowitz A, Hilton HG, Gleimer M, Brodsky FM, Parham P. A Distinctive Cytoplasmic Tail Contributes to Low Surface Expression and Intracellular Retention of the Patr-AL MHC Class I Molecule. J Immunol. 2015 Oct 15; 195(8):3725-36.
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  2. Brodsky FM, Sosa RT, Ybe JA, O'Halloran TJ. Unconventional functions for clathrin, ESCRTs, and other endocytic regulators in the cytoskeleton, cell cycle, nucleus, and beyond: links to human disease. Cold Spring Harb Perspect Biol. 2014 Sep; 6(9):a017004.
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  3. Majeed SR, Vasudevan L, Chen CY, Luo Y, Torres JA, Evans TM, Sharkey A, Foraker AB, Wong NM, Esk C, Freeman TA, Moffett A, Keen JH, Brodsky FM. Clathrin light chains are required for the gyrating-clathrin recycling pathway and thereby promote cell migration. Nat Commun. 2014; 5:3891.
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  4. Vassilopoulos S, Gentil C, Lainé J, Buclez PO, Franck A, Ferry A, Précigout G, Roth R, Heuser JE, Brodsky FM, Garcia L, Bonne G, Voit T, Piétri-Rouxel F, Bitoun M. Actin scaffolding by clathrin heavy chain is required for skeletal muscle sarcomere organization. J Cell Biol. 2014 May 12; 205(3):377-93.
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  5. Sullivan CS, Scheib JL, Ma Z, Dang RP, Schafer JM, Hickman FE, Brodsky FM, Ravichandran KS, Carter BD. The adaptor protein GULP promotes Jedi-1-mediated phagocytosis through a clathrin-dependent mechanism. Mol Biol Cell. 2014 Jun 15; 25(12):1925-36.
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  6. Asensio CS, Sirkis DW, Maas JW, Egami K, To TL, Brodsky FM, Shu X, Cheng Y, Edwards RH. Self-assembly of VPS41 promotes sorting required for biogenesis of the regulated secretory pathway. Dev Cell. 2013 Nov 25; 27(4):425-37.
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  7. Hoshino S, Sakamoto K, Vassilopoulos S, Camus SM, Griffin CA, Esk C, Torres JA, Ohkoshi N, Ishii A, Tamaoka A, Funke BH, Kucherlapati R, Margeta M, Rando TA, Brodsky FM. The CHC22 clathrin-GLUT4 transport pathway contributes to skeletal muscle regeneration. PLoS One. 2013; 8(10):e77787.
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  8. Brodsky F. Frances Brodsky: so you think you know all about clathrin? Interview by Caitlin Sedwick. J Cell Biol. 2013 Sep 16; 202(6):830-1.
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  9. Stachowiak JC, Brodsky FM, Miller EA. A cost-benefit analysis of the physical mechanisms of membrane curvature. Nat Cell Biol. 2013 Sep; 15(9):1019-27.
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  10. Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R, Yanamandra K, Ouidja MO, Brodsky FM, Marasa J, Bagchi DP, Kotzbauer PT, Miller TM, Papy-Garcia D, Diamond MI. Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc Natl Acad Sci U S A. 2013 Aug 13; 110(33):E3138-47.
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  11. Young A, Stoilova-McPhie S, Rothnie A, Vallis Y, Harvey-Smith P, Ranson N, Kent H, Brodsky FM, Pearse BM, Roseman A, Smith CJ. Hsc70-induced changes in clathrin-auxilin cage structure suggest a role for clathrin light chains in cage disassembly. Traffic. 2013 Sep; 14(9):987-96.
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  12. Bonazzi M, Kühbacher A, Toledo-Arana A, Mallet A, Vasudevan L, Pizarro-Cerdá J, Brodsky FM, Cossart P. A common clathrin-mediated machinery co-ordinates cell-cell adhesion and bacterial internalization. Traffic. 2012 Dec; 13(12):1653-66.
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  13. Foraker AB, Camus SM, Evans TM, Majeed SR, Chen CY, Taner SB, Corrêa IR, Doxsey SJ, Brodsky FM. Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG. J Cell Biol. 2012 Aug 20; 198(4):591-605.
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  14. Brodsky FM. Diversity of clathrin function: new tricks for an old protein. Annu Rev Cell Dev Biol. 2012; 28:309-36.
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  15. Brodsky FM, Thattai M, Mayor S. Evolutionary cell biology: Lessons from diversity. Nat Cell Biol. 2012 Jul; 14(7):651.
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  16. Bonazzi M, Vasudevan L, Mallet A, Sachse M, Sartori A, Prevost MC, Roberts A, Taner SB, Wilbur JD, Brodsky FM, Cossart P. Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization. J Cell Biol. 2011 Oct 31; 195(3):525-36.
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  17. Stoddart A, Tennant TR, Fernald AA, Anastasi J, Brodsky FM, Le Beau MM. The clathrin-binding domain of CALM-AF10 alters the phenotype of myeloid neoplasms in mice. Oncogene. 2012 Jan 26; 31(4):494-506.
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  18. Shieh JC, Schaar BT, Srinivasan K, Brodsky FM, McConnell SK. Endocytosis regulates cell soma translocation and the distribution of adhesion proteins in migrating neurons. PLoS One. 2011; 6(3):e17802.
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  19. Taner SB, Pando MJ, Roberts A, Schellekens J, Marsh SG, Malmberg KJ, Parham P, Brodsky FM. Interactions of NK cell receptor KIR3DL1*004 with chaperones and conformation-specific antibody reveal a functional folded state as well as predominant intracellular retention. J Immunol. 2011 Jan 1; 186(1):62-72.
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  20. Wilbur JD, Hwang PK, Ybe JA, Lane M, Sellers BD, Jacobson MP, Fletterick RJ, Brodsky FM. Conformation switching of clathrin light chain regulates clathrin lattice assembly. Dev Cell. 2010 May 18; 18(5):841-8.
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