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Dean Sheppard, MD


Professor, Department of Medicine, UCSF


Phone: (415) 514-4269 (voice)
Box 2922, UCSF
San Francisco, CA 94143-2922

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Harvard College, Cambridge, MA, A.B., 1972
SUNY at Stony Brook, Stony Brook, NY, M.D., 1975, Medicine
Univ of Washington, Seattle, WA, Resident, 1975-78, Internal Medicine
Univ of California, San Francisco, San Francisco, Fellow, 1978-80, Pulmonary

Professional Experience

  • 1986-present
    Director, Lung Biology Center, University of California, San Francisco
  • 1981-87
    Assistant Professor of Medicine, University of California, San Francisco
  • 1987-92
    Associate Professor of Medicine, University of California, San Francisco
  • 1992-present
    Professor of Medicine, University of California, San Francisco
  • 1997-present
    Associate Chair for Biomedical Research, Department of Medicine, UCSF
  • 2000-present
    Member, NHLBI Program Project Review Committee. 1998-2002, Chair 2000-2002
  • 2004-present
    Member, Lung Injury and Repair Study Section

Honors & Awards

  • Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, Sheppard D, Mohrs M, Donaldson DD, Locksley RM, Corry DB. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998; 282:226-228.
  • Munger JS, Huang XZ , Kawakatsu H , Griffiths MJD, Dalton SL, Wu JF, Pittet JF, Kaminiski N, Garat C, Matthay MA, Rifkin DB, Sheppard D. The integrin avb6 binds and activates latent TGFb1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999; 96:319-328.
  • Taaoka Y, J Chen, T Yednock and D Sheppard. The integrin a9b1 mediates adhesion to activated endothelial cells and trans-endothelial neutrophil migration through interaction with vascular cell adhesion molecule 1. J Cell Biol 1999; 145:413-420.
  • Kaminski N, Allard J, Pittet J-F, Zuo F, Griffiths MJD, Morris D, Huang XZ, Sheppard D, Heller RA. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and remodeling. Proc Nat Acad Sci 2000; 97:1778-1783.
  • Huang XZ, Griffiths M, Wu JF, Farese RV, Sheppard D. Impaired cell migration and adhesion but normal development in b5 deficient mice. Mol Cell Biol 2000; 20:755-759.
  • Huang XZ, Wu JF, Ferrando R, Lee JH, Wang YL, Farese RV Jr, Sheppard D. Fatal bilateral chylothorax in mice lacking the integrin a9b1. Mol Cell Biol 2000; 20:5208-5215.
  • Marcinkiewicz C, Taooka Y, Yokosaki Y, Calvete JJ, Marcinkiewicz MM, Lobb RR, Niewiarowski S, Sheppard D. Inhibitory effects of MLDG-containing heterodimeric disintegrins reveal distinct structural requirements for interaction of the integrin a9b1 with VCAM-1, tenascin-C and osteopontin. J Biol Chem 2000; 275:31930-31937.
  • Miller LC, Blakemore W, Sheppard D, Atakilit AA, King AMQ, Jackson T. Role of the cytoplasmic domain of the b subunit of the integrin avb6 in infection by foot and mouth disease virus. J Virology 2001, 75:4158-4164.
  • Pittet J-F, Griffiths MJD, Geiser T, Kaminski N, Dalton SL, Huang X, Brown LAS, Gotwals PJ, Koetiansky VE, Matthay MA, Sheppard D. TGFb is a critical mediator of acute lung injury. J Clin Invest 2001; 107:1529-1536.
  • Young BA, Taooka Y, Liu S, Askins J, Yokosaki Y, Thomas SM, Sheppard D. The cytoplasmic domain of the integrin a9 subunit requires the adaptor protein paxillin to inhibit cell spreading but promotes cell migration in a paxillin-independent manner. Mol Biol Cell 2001; 12:3214-3225.
  • Reynolds LE, Wyder L, Lively JG, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, Hodivala-Dilke KM. Enhanced angiogenesis in b3 integrin-deficient and b3/b5 integrin-deficient mice. Nature Medicine 2002; 8:27-34.
  • Jackson T, Mould PA, Sheppard D, King AMQ. The integrin avb1 is a receptor for foot-and-mouth disease virus. J Virology 2002; 76:935-941.
  • Elicieri BP, Puente XS, Hood JD, Huang X, Schlaepfer DA, Sheppard D, Cheresh DA. VEGF endothelial response requires src-mediated coupling of FAK to integrin avb5 J. Cell Biol. 2002 157:149-160.
  • Mu D, Cambier S, Fjellbirkeland L, Baron JL, Munger J, Kawakatsu H, Sheppard D, Broaddus VC, Nishimura SL. The integrin avb8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-b1. J Cell Biol 2002 157:493-507.
  • Zuo F, Kaminski N, Fugui E, Allard J, Yakhini Z, Ben-Dor A, Lollini L, Morris D, Kim Y, DeLustro B, Sheppard D, Pardo A, Selman M, Heller R. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc Nat Acad Sci (USA) 2002; 99:6292-6297.
  • Liao YF, Gotwals PJ, Koteliansky VE, Sheppard D, Van de Water L, The EIIIA segment of fibronectin is a ligand for the integrins a9b1 and a4b1 providing a novel mechanism for regulating cell adhesion by alternative splicing. J Biol Chem 2002; 277:14467-14474.
  • Eto K, Huet C, Tarui T, Kupriyanov S, Liu H-Z, Puzon-McLaughlin W, Zhang X-P, Sheppard D, Engvall E, Takada Y. Functional classification of ADAMs based on a conserved motif for binding to integrin a9b1; implications for sperm-egg binding and other cell interactions. J. Biol. Chem 2002 277:17804-10.
  • Knight PA, Wright SH, Brown JK, Huang X, Sheppard D, Miller HRP. Enteric expression of the integrin avb6 is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1. Am J Pathol 2002 161:771-779.
  • Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, Dolganov G, Glick, A, Sheppard D. Loss of integrin avb6-mediated TGFb activation causes Mmp12-dependent emphysema. Nature 2003 422:169-173.
  • Frank J, Roux J, Kawakatsu H, Su G, Dagenais A, Berthiaume Y, Howard MB, Canessa C, Fang XH, Sheppard D, Matthay MA, Pittet JF. TGF-b1 decreases _ENaC expression and alveolar epithelial vectorial sodium and fluid transport via an ERK 1/2-dependent mechanism. J Biol Chem 2003 278:43939-43950.
  • Ma L-J, Yang H, Gaspert H, Carlesso G, Davidson JM, Sheppard D, Fogo AM, Transforming growth factor-b dependent and independent pathways of induction of tubulointerstitial fibrosis in b6-/- mice Am J Pathol 2003 163:1261-73.
  • Lind DL, Choudhry S, Ung N, Ziv E, Avila PC, Coyle NE, Salari K, Nazario S, Casal J, Torres A, Rodriguez-Santana AJ, Matallana H, Lilly CM, Salas J, Selman M, Boushey HA, Weiss ST, Chapela R, Ford JG, Rodriguez-Cintron W, Silverman EK, Sheppard D, Kwok P-Y and Burchard EG. ADAM33 is not associated with asthma in Latino populations. Am J Respir Crit Care Med 2003 168:1312-1316.
  • Bazan-Socha S, Kisiel DG, Young B, Theakston DG, Calvete JJ, Sheppard D, Marcinkiewicz C. Structural requirements of MLD-containing disintegrins for functional interactions with a4b1 and a9b1 integrins. Biochemistry 2004 43:1639-1647.
  • Weinreb PH, Simon KJ, Rayborn P, Yang WJ, Leone DR, Dolinski BM, Yokota Y, Kawakatsu H, Atakilit A, Sheppard D, Violette SM. Function-blocking integrin avb6 antibodies: Distinct ligand mimetic and non-ligand-mimetic classes. J Biol Chem 2004 279:17875-87.
  • Chen C, Young BA, Coleman CS, Pegg AE, Sheppard D. Spermidine/Spermine N1-Acetyltransferase specifically binds to the integrin a9 subunit cytoplasmic domain and enhances cell migration J Cell Biol 2004 (in press).

Selected Publications

  1. Erle DJ, Sheppard D. The cell biology of asthma. J Cell Biol. 2014 Jun 9; 205(5):621-31.
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  2. Ito K, Morimoto J, Kihara A, Matsui Y, Kurotaki D, Kanayama M, Simmons S, Ishii M, Sheppard D, Takaoka A, Uede T. Integrin a9 on lymphatic endothelial cells regulates lymphocyte egress. Proc Natl Acad Sci U S A. 2014 Feb 25; 111(8):3080-5.
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  3. Madala SK, Korfhagen TR, Schmidt S, Davidson C, Edukulla R, Ikegami M, Violette SM, Weinreb PH, Sheppard D, Hardie WD. Inhibition of the avß6 integrin leads to limited alteration of TGF-a-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2014 Apr; 306(8):L726-35.
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  4. Blackwell TS, Tager AM, Borok Z, Moore BB, Schwartz DA, Anstrom KJ, Bar-Joseph Z, Bitterman P, Blackburn MR, Bradford W, Brown KK, Chapman HA, Collard HR, Cosgrove GP, Deterding R, Doyle R, Flaherty KR, Garcia CK, Hagood JS, Henke CA, Herzog E, Hogaboam CM, Horowitz JC, King TE, Loyd JE, Lawson WE, Marsh CB, Noble PW, Noth I, Sheppard D, Olsson J, Ortiz LA, O'Riordan TG, Oury TD, Raghu G, Roman J, Sime PJ, Sisson TH, Tschumperlin D, Violette SM, Weaver TE, Wells RG, White ES, Kaminski N, Martinez FJ, Wynn TA, Thannickal VJ, Eu JP. Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report. Am J Respir Crit Care Med. 2014 Jan 15; 189(2):214-22.
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  5. Travis MA, Sheppard D. TGF-ß Activation and Function in Immunity. Annu Rev Immunol. 2014 Mar 21; 32:51-82.
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  6. Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG, Griggs DW, Prinsen MJ, Maher JJ, Iredale JP, Lacy-Hulbert A, Adams RH, Sheppard D. Targeting of av integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013 Dec; 19(12):1617-24.
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  7. Goh YP, Henderson NC, Heredia JE, Red Eagle A, Odegaard JI, Lehwald N, Nguyen KD, Sheppard D, Mukundan L, Locksley RM, Chawla A. Eosinophils secrete IL-4 to facilitate liver regeneration. Proc Natl Acad Sci U S A. 2013 Jun 11; 110(24):9914-9.
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  8. Katsumoto TR, Kudo M, Chen C, Sundaram A, Callahan EC, Zhu JW, Lin J, Rosen CE, Manz BN, Lee JW, Matthay MA, Huang X, Sheppard D, Weiss A. The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases. J Clin Invest. 2013 May 1; 123(5):2037-48.
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  9. Sheppard D. ROCKing pulmonary fibrosis. J Clin Invest. 2013 Mar 1; 123(3):1005-6.
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  10. Su G, Atakilit A, Li JT, Wu N, Luong J, Chen R, Bhattacharya M, Sheppard D. Effective treatment of mouse sepsis with an inhibitory antibody targeting integrin avß5. Crit Care Med. 2013 Feb; 41(2):546-53.
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  11. Friedman SL, Sheppard D, Duffield JS, Violette S. Therapy for fibrotic diseases: nearing the starting line. Sci Transl Med. 2013 Jan 9; 5(167):167sr1.
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  12. Freimuth J, Clermont FF, Huang X, DeSapio A, Tokuyasu TA, Sheppard D, Akhurst RJ. Epistatic interactions between Tgfb1 and genetic loci, Tgfbm2 and Tgfbm3, determine susceptibility to an asthmatic stimulus. Proc Natl Acad Sci U S A. 2012 Oct 30; 109(44):18042-7.
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  13. Henderson NC, Sheppard D. Integrin-mediated regulation of TGFß in fibrosis. Biochim Biophys Acta. 2013 Jul; 1832(7):891-6.
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  14. Huang F, Zhang H, Wu M, Yang H, Kudo M, Peters CJ, Woodruff PG, Solberg OD, Donne ML, Huang X, Sheppard D, Fahy JV, Wolters PJ, Hogan BL, Finkbeiner WE, Li M, Jan YN, Jan LY, Rock JR. Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction. Proc Natl Acad Sci U S A. 2012 Oct 2; 109(40):16354-9.
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  15. Chen C, Kudo M, Rutaganira F, Takano H, Lee C, Atakilit A, Robinett KS, Uede T, Wolters PJ, Shokat KM, Huang X, Sheppard D. Integrin a9ß1 in airway smooth muscle suppresses exaggerated airway narrowing. J Clin Invest. 2012 Aug 1; 122(8):2916-27.
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  16. Sheppard D. Modulation of acute lung injury by integrins. Proc Am Thorac Soc. 2012 Jul; 9(3):126-9.
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  17. Thornton EE, Looney MR, Bose O, Sen D, Sheppard D, Locksley R, Huang X, Krummel MF. Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung. J Exp Med. 2012 Jun 4; 209(6):1183-99.
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  18. Bhattacharya M, Su G, Su X, Oses-Prieto JA, Li JT, Huang X, Hernandez H, Atakilit A, Burlingame AL, Matthay MA, Sheppard D. IQGAP1 is necessary for pulmonary vascular barrier protection in murine acute lung injury and pneumonia. Am J Physiol Lung Cell Mol Physiol. 2012 Jul 1; 303(1):L12-9.
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  19. Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, Wang Y, Bernstein X, Li JT, Atabai K, Huang X, Sheppard D. IL-17A produced by aß T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med. 2012 Apr; 18(4):547-54.
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  20. Doherty TA, Khorram N, Sugimoto K, Sheppard D, Rosenthal P, Cho JY, Pham A, Miller M, Croft M, Broide DH. Alternaria induces STAT6-dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness. J Immunol. 2012 Mar 15; 188(6):2622-9.
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