George H. Caughey, MD

George H. Caughey, MD

Professor, Department of Medicine, UCSF; Chief of Pulmonary and Critical Care Medicine, San Francisco VA Medical Center
Julius and Lilian Nadel Endowed Chair, UCSF

Phone: (415) 221-4810 x2385 (voice)
Mail Box 111-D, Veterans Affairs Medical Center, San Francisco, CA 94121

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Cancer Center Membership

Associate Member » Cancer, Immunity, and Microenvironment

Research Summary

Defining Functions for Epithelial and Inflammatory Cell Proteases in Lung Diseases

The Caughey lab is interested in understanding how protein-cleaving enzymes of mast cells, white blood cells, and cells lining the airway contribute to inflammation, host defense, tissue remodeling and barrier function in the lung. These studies relate to clinical problems in asthma, cystic fibrosis, bronchitis, lung transplantation and bacterial pneumonia. These areas of research are especially related to veterans who have inhaled toxins, who smoke cigarettes, who have received allografts to treat end-stage lung disease, or have lung and bronchial infections. The Caughey lab is perhaps best known for his work with mast cells, which play major roles in allergic diseases, including asthma and fatal reactions to bee stings. He has focused on mast cell proteases, which are enzymes that break down proteins. Over the past decade, the Caughey lab has developed several compelling lines of evidence to suggest that these proteases play deleterious roles in allergic diseases. This work has assisted pharmaceutical development of new classes of anti-inflammatory drugs to treat asthma and other diseases involving mast cells. More recently, he has focused on the positive contributions of mast cells and their proteases to host defense against bacteria and other pathogens, on their role in modulating the inflammatory response to infection, and on defining genetic variation in mast cell protease genes that influence diseases like asthma.


Arizona State University, BS, 1975, Chemistry
Stanford University School of Medicine, MD, 1979, Medicine
Pennsylvania Hospital, 1982, Internal Medicine
University of California, San Francisco, 1986, Pulmonary Medicine

Professional Experience

  • 1988-92
    Assistant Professor, Dept. of Medicine, UCSF
  • 1988-98
    Associate Staff, Cardiovascular Research Institute, UCSF
  • 1992-98
    Associate Professor, Dept. of Medicine, UCSF
  • 1992-present
    Molecular Medicine Program Faculty, UCSF
  • 1995-present
    Editorial Board, American Journal of Respiratory Cell and Molecular Biology
  • 1996-present
    Member of UCSF Graduate Program in Biomedical Sciences
  • 1998-present
    Professor, Dept. of Medicine, UCSF
  • 1999-present
    Associate Director, UCSF Adult Cystic Fibrosis Program
  • 1999-present
    Investigator, Cardiovascular Research Institute, UCSF
  • 2002-present
    Editorial Boards: FASEB Journal and Journal of Childrens Health
  • 2002-present
    Member, UCSF Cancer Center and Center for Neurobiology of Digestive Disease
  • 2004-present
    Editorial Board, Current Respiratory Medicine Reviews
  • 2004-present
    Chief of Pulmonary and Critical Care Medicine, San Francisco VA Medical Center

Honors & Awards

  • 1974
    American Chemical Society Outstanding Undergraduate Award, ASU
  • 1975
    Phi Beta Kappa and Merck Award in Chemistry, ASU
  • 1986
    NIH Clinical Investigator Award
  • 1992
    American Lung Association Career Investigator Award
  • 1992
    Elected to American Society for Clinical Investigation
  • 2000
    Elected to American Association of Physicians
  • 2004
    Recipient of Julius and Lillian Endowed Chair of Medicine

Selected Publications

  1. Nimishakavi S, Raymond WW, Gruenert DC, Caughey GH. Divergent Inhibitor Susceptibility among Airway Lumen-Accessible Tryptic Proteases. PLoS One. 2015; 10(10):e0141169.
    View on PubMed
  2. Raymond WW, Xu X, Nimishakavi S, Le C, McDonald DM, Caughey GH. Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux. PLoS One. 2015; 10(5):e0125797.
    View on PubMed
  3. Bose O, Baluk P, Looney MR, Cheng LE, McDonald DM, Caughey GH, Krummel MF. Mast Cells Present Protrusions into Blood Vessels upon Tracheal Allergen Challenge in Mice. PLoS One. 2015; 10(3):e0118513.
    View on PubMed
  4. Greenland JR, Xu X, Sayah DM, Liu FC, Jones KD, Looney MR, Caughey GH. Mast cells in a murine lung ischemia-reperfusion model of primary graft dysfunction. Respir Res. 2014; 15:95.
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  5. Sutherland RE, Barry SS, Olsen JS, Salantes DB, Caughey GH, Wolters PJ. Dipeptidyl peptidase I controls survival from Klebsiella pneumoniae lung infection by processing surfactant protein D. Biochem Biophys Res Commun. 2014 Jul 18; 450(1):818-23.
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  6. Greenland JR, Jewell NP, Gottschall M, Trivedi NN, Kukreja J, Hays SR, Singer JP, Golden JA, Caughey GH. Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection. Am J Transplant. 2014 Apr; 14(4):831-40.
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  7. Xu X, Greenland J, Baluk P, Adams A, Bose O, McDonald DM, Caughey GH. Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis. Am J Respir Cell Mol Biol. 2013 Sep; 49(3):437-44.
    View on PubMed
  8. Chau JY, Tiffany CM, Nimishakavi S, Lawrence JA, Pakpour N, Mooney JP, Lokken KL, Caughey GH, Tsolis RM, Luckhart S. Malaria-associated L-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal Salmonella bacteremia. Infect Immun. 2013 Oct; 81(10):3515-26.
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  9. Raman K, Trivedi NN, Raymond WW, Ganesan R, Kirchhofer D, Verghese GM, Craik CS, Schneider EL, Nimishakavi S, Caughey GH. Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors. J Biol Chem. 2013 Apr 12; 288(15):10588-98.
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  10. Greenland JR, Jones KD, Hays SR, Golden JA, Urisman A, Jewell NP, Caughey GH, Trivedi NN. Association of large-airway lymphocytic bronchitis with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2013 Feb 15; 187(4):417-23.
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  11. Nimishakavi S, Besprozvannaya M, Raymond WW, Craik CS, Gruenert DC, Caughey GH. Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2012 Jul; 303(2):L97-106.
    View on PubMed
  12. Sugimoto K, Kudo M, Sundaram A, Ren X, Huang K, Bernstein X, Wang Y, Raymond WW, Erle DJ, Abrink M, Caughey GH, Huang X, Sheppard D. The avß6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells. J Clin Invest. 2012 Feb 1; 122(2):748-58.
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  13. Sutherland RE, Xu X, Kim SS, Seeley EJ, Caughey GH, Wolters PJ. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice. PLoS One. 2011; 6(11):e27564.
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  14. Xu X, Zhang H, Song Y, Lynch SV, Lowell CA, Wiener-Kronish JP, Caughey GH. Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa. J Leukoc Biol. 2012 Feb; 91(2):275-84.
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  15. Caughey GH. Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol. 2011; 716:212-34.
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  16. Raymond WW, Trivedi NN, Makarova A, Ray M, Craik CS, Caughey GH. How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution. J Immunol. 2010 Nov 1; 185(9):5360-8.
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  17. Dougherty RH, Sidhu SS, Raman K, Solon M, Solberg OD, Caughey GH, Woodruff PG, Fahy JV. Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma. J Allergy Clin Immunol. 2010 May; 125(5):1046-1053.e8.
    View on PubMed
  18. Trivedi NN, Caughey GH. Mast cell peptidases: chameleons of innate immunity and host defense. Am J Respir Cell Mol Biol. 2010 Mar; 42(3):257-67.
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  19. Trivedi NN, Tamraz B, Chu C, Kwok PY, Caughey GH. Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutations. J Allergy Clin Immunol. 2009 Nov; 124(5):1099-105.e1-4.
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  20. Innes AL, Carrington SD, Thornton DJ, Kirkham S, Rousseau K, Dougherty RH, Raymond WW, Caughey GH, Muller SJ, Fahy JV. Ex vivo sputum analysis reveals impairment of protease-dependent mucus degradation by plasma proteins in acute asthma. Am J Respir Crit Care Med. 2009 Aug 1; 180(3):203-10.
    View on PubMed

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