University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Harold A. Chapman, MD

Harold A. Chapman, MD

Professor, Department of Medicine, UCSF

Cancer Center Program Memberships

Affiliate Member

Research Summary

The Chapman lab has had a longstanding interest and track record of innovation in the field of tissue remodeling, particularly as it relates to lung disease. For many years my work primarily focused on proteolytic enzymes. My group and I cloned and characterized several new members of the cathepsin family and elucidated their roles in bone, brain, lung, and immune disorders. I also pursued basic mechanisms by which proteases and adhesion receptors coordinate cell invasion and extracellular matrix remodeling and this has led to longstanding interest in integrin signaling. We were the first to recognize the physical and functional connections between integrins and the key cell surface protease, plasminogen activator. After moving from Harvard to UCSF 12 years ago I focused my lab on pulmonary fibrosis as a disorder of great unmet medical need and a logical extension of my prior work in matrix biology. I pioneered the in vivo investigation of the role of epithelial mesenchymal transition (EMT) in pulmonary fibrosis and uncovered mechanistic insight as to how integrins and hypoxia regulate epithelial cell plasticity. These studies have provided a roadmap for defining the role of EMT signaling in human fibrosis and lung cancer. More recently we have extended our studies of epithelial plasticity into the realm of lung stem/progenitor cells and are committed to defining the regenerative potential of the lung after injury.

I have trained approximately twenty PhD and/or MD post-docs who now populate academic departments and pharmaceutical labs. As a physician scientist myself, I have particularly enjoyed the responsibility of motivating and training capable young physicians for careers in disease-oriented research. These now include Division and Department Chairs as well as several independent medicine faculty with successful NIH-funded research programs. My lab now is comprised of mainly PhD trainees and junior faculty and we are committed to understanding and targeting the emerging relationship between hypoxia, EMT, and tissue remodeling during fibrogenesis and cancer progression.

Education

Tulane University, 1968, Premedical
University of Alabama School of Medicine, M.D., 1972, Medicine


Professional Experience

  • 1972-1975
    Residency Training in Internal Medicine, University of Utah Affiliated Hospitals, Salt Lake City, UT
  • 1975-1977
    Associate Investigator, V.A. Medical Center, Salt Lake City, UT
  • 1978-1979
    Pulmonary Fellow, University of Utah Affiliated Hospitals, Salt Lake City, UT
  • 1979-1982
    Research Associate in Immunology, V.A. Medical Center, Salt Lake City, UT
  • 1979-1985
    Assistant Professor of Medicine, University of Utah, Department of Medicine, Salt Lake City, UT
  • 1985
    Associate Professor of Medicine, University of Utah, Department of Medicine, Salt Lake City UT
  • 1985-1999
    Associate Professor of Medicine, Harvard Medical School, Department of Medicine, Boston, MA
  • 1992-1999
    Physician, Brigham and Women's Hospital, Boston, MA
  • 1992-1999
    Associate Professor of Environmental Health, Harvard School of Public Health, Boston, MA
  • 2000
    Chief, Pulmonary and Critical Care Medicine Division, University of California, San Francisco
  • 2000
    Professor of Medicine, University of California, San Francisco
  • 2000
    Senior Member, Cardiovascular Research Institute, University of California San Francisco

Honors & Awards

  • 1972
    Alpha Omega Alpha, University of Alabama School of Medicine
  • 1985-1990
    Career Investigator Award, American Lung Association
  • 1987
    American Society for Clinical Investigation
  • 1998
    American Association of Physicians
  • 2001
    MERIT Award, NIH/NHLBI

Selected Publications

  1. Wang C, Reyes de Mochel NS, Christenson SA, Cassandras M, Moon R, Brumwell AN, Byrnes LE, Li A, Yokosaki Y, Shan P, Sneddon JB, Jablons D, Lee PJ, Matthay MA, Chapman HA, Peng T. Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype. J Clin Invest. 2018 Jul 12.
    View on PubMed
  2. Jourdan Le Saux C, Chapman HA. Idiopathic Pulmonary Fibrosis: Cell Death and Inflammation Revisited. Am J Respir Cell Mol Biol. 2018 Apr 26.
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  3. Kim KK, Sheppard D, Chapman HA. TGF-ß1 Signaling and Tissue Fibrosis. Cold Spring Harb Perspect Biol. 2018 Apr 02; 10(4).
    View on PubMed
  4. Zhou Y, Horowitz JC, Naba A, Ambalavanan N, Atabai K, Balestrini J, Bitterman PB, Corley RA, Ding BS, Engler AJ, Hansen KC, Hagood JS, Kheradmand F, Lin QS, Neptune E, Niklason L, Ortiz LA, Parks WC, Tschumperlin DJ, White ES, Chapman HA, Thannickal VJ. Extracellular matrix in lung development, homeostasis and disease. Matrix Biol. 2018 Mar 08.
    View on PubMed
  5. Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA. Fibroblast-specific inhibition of TGF-ß1 signaling attenuates lung and tumor fibrosis. J Clin Invest. 2017 Oct 02; 127(10):3675-3688.
    View on PubMed
  6. Xi Y, Kim T, Brumwell AN, Driver IH, Wei Y, Tan V, Jackson JR, Xu J, Lee DK, Gotts JE, Matthay MA, Shannon JM, Chapman HA, Vaughan AE. Local lung hypoxia determines epithelial fate decisions during alveolar regeneration. Nat Cell Biol. 2017 Aug; 19(8):904-914.
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  7. McClendon J, Jansing NL, Redente EF, Gandjeva A, Ito Y, Colgan SP, Ahmad A, Riches DWH, Chapman HA, Mason RJ, Tuder RM, Zemans RL. Hypoxia-Inducible Factor 1a Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury. Am J Pathol. 2017 Aug; 187(8):1772-1786.
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  8. Vaughan AE, Chapman HA. Failure of Alveolar Type 2 Cell Maintenance Links Neonatal Distress with Adult Lung Disease. Am J Respir Cell Mol Biol. 2017 04; 56(4):415-416.
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  9. Kanegai CM, Xi Y, Donne ML, Gotts JE, Driver IH, Amidzic G, Lechner AJ, Jones KD, Vaughan AE, Chapman HA, Rock JR. Persistent Pathology in Influenza-Infected Mouse Lungs. Am J Respir Cell Mol Biol. 2016 10; 55(4):613-615.
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  10. Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG, Treutlein B, Tan K, Tan V, Liu FC, Looney MR, Matthay MA, Rock JR, Chapman HA. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature. 2015 Jan 29; 517(7536):621-5.
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  11. 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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  12. Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, Niklason L, Calle E, Le A, Randell SH, Rock J, Snitow M, Krummel M, Stripp BR, Vu T, White ES, Whitsett JA, Morrisey EE. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell. 2014 Aug 07; 15(2):123-38.
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  13. Reiser J, Chapman H. Soluble urokinase-type plasminogen activator receptor in FSGS: stirred but not shaken. J Am Soc Nephrol. 2014 Aug; 25(8):1611-3.
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  14. Grove LM, Southern BD, Jin TH, White KE, Paruchuri S, Harel E, Wei Y, Rahaman SO, Gladson CL, Ding Q, Craik CS, Chapman HA, Olman MA. Urokinase-type plasminogen activator receptor (uPAR) ligation induces a raft-localized integrin signaling switch that mediates the hypermotile phenotype of fibrotic fibroblasts. J Biol Chem. 2014 May 02; 289(18):12791-804.
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  15. 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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  16. Xi Y, Tan K, Brumwell AN, Chen SC, Kim YH, Kim TJ, Wei Y, Chapman HA. Inhibition of epithelial-to-mesenchymal transition and pulmonary fibrosis by methacycline. Am J Respir Cell Mol Biol. 2014 Jan; 50(1):51-60.
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  17. Shum AK, Alimohammadi M, Tan CL, Cheng MH, Metzger TC, Law CS, Lwin W, Perheentupa J, Bour-Jordan H, Carel JC, Husebye ES, De Luca F, Janson C, Sargur R, Dubois N, Kajosaari M, Wolters PJ, Chapman HA, Kämpe O, Anderson MS. BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease. Sci Transl Med. 2013 Oct 09; 5(206):206ra139.
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  18. Yang J, Wheeler SE, Velikoff M, Kleaveland KR, LaFemina MJ, Frank JA, Chapman HA, Christensen PJ, Kim KK. Activated alveolar epithelial cells initiate fibrosis through secretion of mesenchymal proteins. Am J Pathol. 2013 Nov; 183(5):1559-1570.
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  19. Matthay MA, Anversa P, Bhattacharya J, Burnett BK, Chapman HA, Hare JM, Hei DJ, Hoffman AM, Kourembanas S, McKenna DH, Ortiz LA, Ott HC, Tente W, Thébaud B, Trapnell BC, Weiss DJ, Yuan JX, Blaisdell CJ. Cell therapy for lung diseases. Report from an NIH-NHLBI workshop, November 13-14, 2012. Am J Respir Crit Care Med. 2013 Aug 01; 188(3):370-5.
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  20. Morrisey EE, Cardoso WV, Lane RH, Rabinovitch M, Abman SH, Ai X, Albertine KH, Bland RD, Chapman HA, Checkley W, Epstein JA, Kintner CR, Kumar M, Minoo P, Mariani TJ, McDonald DM, Mukouyama YS, Prince LS, Reese J, Rossant J, Shi W, Sun X, Werb Z, Whitsett JA, Gail D, Blaisdell CJ, Lin QS. Molecular determinants of lung development. Ann Am Thorac Soc. 2013 Apr; 10(2):S12-6.
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