University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Dean Sheppard, MD

Dean Sheppard, MD

Professor, Department of Medicine, UCSF

Cancer Center Program Memberships

Non-aligned

Research Summary

Dean Sheppard is a Professor of Medicine, Chief of the Division of Pulmonary, Critical Care, Allergy and Sleep and director of the Lung Biology Center. His research focuses on the molecular mechanisms underlying pulmonary (and other organ) fibrosis, asthma and acute lung injury. One aim of the research is to identify new therapeutic targets to ultimately improve the treatment of each of these common diseases. The work begins with basic investigation of how cells use members of the integrin family to detect, modify and respond to spatially restricted extracellular clues and how these responses contribute to the development of common lung diseases. Utilizing mice with global or conditional knockouts of the epithelial-restricted integrin, avß6, and the widely expressed integrins, a5ß1, a9ß1, avß5 and avß8, the lab has identified important roles for these integrins in models of each common lung disease and key steps upstream and downstream of the integrins that provide potential therapeutic targets. His lab identified the unique roles that 3 integrins, avß1, avß6 and avß8 play in activation of the growth factor, latent transforming growth factor beta (TGFß) and has identified critical roles for this process in acute lung injury, pulmonary fibrosis, post-natal brain development and immunosuppression in the setting of cancer. The lab has partnered with academic colleagues, biotech and pharmaceutical companies to develop novel antibody and small molecule inhibitors of these integrins that are in various stages of pre-clinical and clinical development. Current work is also using single cell RNA sequencing to understand the heterogeneity of cells that contribute to tissue fibrosis in the lung, skin, kidney, liver and central nervous system and is exploring the potential of engineering T cells for local delivery of novel therapeutics to fibrotic organs.

Education

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

  • 1992
    Elected Member, American Society for Clinical Investigation
  • 1995
    Elected Member, Association of American Physicians
  • 1995
    Clean Air Award, California Lung Association
  • 1998
    Scientific Achievement Award, American Thoracic Society
  • 2004-2014
    NIH Merit Award
  • 2013
    Top 20 Translational Scientists, Nature Biotechnology
  • 2016
    UCSF Fraculty Research Lecture in Translational Science
  • 2017
    elected to American Academy of Arts and Sciences

Selected Publications

  1. Tsujino K, Li JT, Tsukui T, Ren X, Bakiri L, Wagner EF, Sheppard D. Fra-2 negatively regulates postnatal alveolar septation by modulating myofibroblast function. Am J Physiol Lung Cell Mol Physiol. 2017 Aug 17; ajplung.00062.2017.
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  2. Jenkins RG, Moore BB, Chambers RC, Eickelberg O, Königshoff M, Kolb M, Laurent GJ, Nanthakumar CB, Olman MA, Pardo A, Selman M, Sheppard D, Sime PJ, Tager AM, Tatler AL, Thannickal VJ, White ES. An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2017 May; 56(5):667-679.
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  3. Sheppard DM, Li J, Henbest KB, Neil SR, Maeda K, Storey J, Schleicher E, Biskup T, Rodriguez R, Weber S, Hore PJ, Timmel CR, Mackenzie SR. Millitesla magnetic field effects on the photocycle of an animal cryptochrome. Sci Rep. 2017 Feb 08; 7:42228.
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  4. Sundaram A, Chen C, Khalifeh-Soltani A, Atakilit A, Ren X, Qiu W, Jo H, DeGrado W, Huang X, Sheppard D. Targeting integrin a5ß1 ameliorates severe airway hyperresponsiveness in experimental asthma. J Clin Invest. 2017 Jan 03; 127(1):365-374.
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  5. Tsujino K, Reed NI, Atakilit A, Ren X, Sheppard D. Transforming growth factor-ß plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma. Am J Physiol Lung Cell Mol Physiol. 2017 Jan 01; 312(1):L22-L31.
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  6. Reed NI, Tang YZ, McIntosh J, Wu Y, Molnar KS, Civitavecchia A, Sheppard D, DeGrado WF, Jo H. Exploring N-Arylsulfonyl-l-proline Scaffold as a Platform for Potent and Selective avß1 Integrin Inhibitors. ACS Med Chem Lett. 2016 Oct 13; 7(10):902-907.
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  7. Meliopoulos VA, Van de Velde LA, Van de Velde NC, Karlsson EA, Neale G, Vogel P, Guy C, Sharma S, Duan S, Surman SL, Jones BG, Johnson MD, Bosio C, Jolly L, Jenkins RG, Hurwitz JL, Rosch JW, Sheppard D, Thomas PG, Murray PJ, Schultz-Cherry S. An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens. PLoS Pathog. 2016 Aug; 12(8):e1005804.
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  8. McAleer JP, Nguyen NL, Chen K, Kumar P, Ricks DM, Binnie M, Armentrout RA, Pociask DA, Hein A, Yu A, Vikram A, Bibby K, Umesaki Y, Rivera A, Sheppard D, Ouyang W, Hooper LV, Kolls JK. Pulmonary Th17 Antifungal Immunity Is Regulated by the Gut Microbiome. J Immunol. 2016 Jul 01; 197(1):97-107.
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  9. Reboldi A, Arnon TI, Rodda LB, Atakilit A, Sheppard D, Cyster JG. IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches. Science. 2016 May 13; 352(6287):aaf4822.
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  10. Sun KH, Chang Y, Reed NI, Sheppard D. a-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFß activation or collagen production across multiple models of organ fibrosis. Am J Physiol Lung Cell Mol Physiol. 2016 May 01; 310(9):L824-36.
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  11. Mohammed J, Beura LK, Bobr A, Astry B, Chicoine B, Kashem SW, Welty NE, Igyártó BZ, Wijeyesinghe S, Thompson EA, Matte C, Bartholin L, Kaplan A, Sheppard D, Bridges AG, Shlomchik WD, Masopust D, Kaplan DH. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-ß. Nat Immunol. 2016 Apr; 17(4):414-21.
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  12. Tsujino K, Sheppard D. Critical Appraisal of the Utility and Limitations of Animal Models of Scleroderma. Curr Rheumatol Rep. 2016 Jan; 18(1):4.
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  13. Peng ZW, Ikenaga N, Liu SB, Sverdlov DY, Vaid KA, Dixit R, Weinreb PH, Violette S, Sheppard D, Schuppan D, Popov Y. Integrin avß6 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis. Hepatology. 2016 Jan; 63(1):217-32.
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  14. Plaks V, Boldajipour B, Linnemann JR, Nguyen NH, Kersten K, Wolf Y, Casbon AJ, Kong N, van den Bijgaart RJ, Sheppard D, Melton AC, Krummel MF, Werb Z. Adaptive Immune Regulation of Mammary Postnatal Organogenesis. Dev Cell. 2015 Sep 14; 34(5):493-504.
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  15. Li JT, Melton AC, Su G, Hamm DE, LaFemina M, Howard J, Fang X, Bhat S, Huynh KM, O'Kane CM, Ingram RJ, Muir RR, McAuley DF, Matthay MA, Sheppard D. Unexpected Role for Adaptive aßTh17 Cells in Acute Respiratory Distress Syndrome. J Immunol. 2015 Jul 01; 195(1):87-95.
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  16. Reed NI, Jo H, Chen C, Tsujino K, Arnold TD, DeGrado WF, Sheppard D. The avß1 integrin plays a critical in vivo role in tissue fibrosis. Sci Transl Med. 2015 May 20; 7(288):288ra79.
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  17. Sheppard D. Epithelial-mesenchymal interactions in fibrosis and repair. Transforming growth factor-ß activation by epithelial cells and fibroblasts. Ann Am Thorac Soc. 2015 Mar; 12 Suppl 1:S21-3.
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  18. Xu P, Bailey-Bucktrout S, Xi Y, Xu D, Du D, Zhang Q, Xiang W, Liu J, Melton A, Sheppard D, Chapman HA, Bluestone JA, Derynck R. Innate antiviral host defense attenuates TGF-ß function through IRF3-mediated suppression of Smad signaling. Mol Cell. 2014 Dec 18; 56(6):723-37.
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  19. Arnold TD, Niaudet C, Pang MF, Siegenthaler J, Gaengel K, Jung B, Ferrero GM, Mukouyama YS, Fuxe J, Akhurst R, Betsholtz C, Sheppard D, Reichardt LF. Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking aVß8-TGFß signaling in the brain. Development. 2014 Dec; 141(23):4489-99.
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  20. Bhattacharya M, Sundaram A, Kudo M, Farmer J, Ganesan P, Khalifeh-Soltani A, Arjomandi M, Atabai K, Huang X, Sheppard D. IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction. J Clin Invest. 2014 Nov; 124(11):4895-8.
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