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. Divergent Inhibitor Susceptibility among Airway Lumen-Accessible Tryptic Proteases. PLoS One. 2015; 10(10):e0141169.
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  2. Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux. PLoS One. 2015; 10(5):e0125797.
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  3. Mast Cells Present Protrusions into Blood Vessels upon Tracheal Allergen Challenge in Mice. PLoS One. 2015; 10(3):e0118513.
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  4. Mast cells in a murine lung ischemia-reperfusion model of primary graft dysfunction. Respir Res. 2014; 15:95.
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  5. 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. Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection. Am J Transplant. 2014 Apr; 14(4):831-40.
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  7. 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.
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  8. 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. 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. 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. 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.
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  12. 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. 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. 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. Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol. 2011; 716:212-34.
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  16. 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. 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.
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  18. 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. 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. 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.
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