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George Caughey, MD

Title(s)Professor Emeritus, Medicine
SchoolSchool of Medicine
Address90 Medical Center Way
San Francisco CA 94143
Phone415-221-4810 ext. 6385
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    Collapse Biography 
    Collapse Education and Training
    University of California, San FranciscoPost-Doc Fellow/Scholar Medicine
    University of California, San Francisco Clinical Pulmonary Fellowship Medicine
    Pennsylvania HospitalResidency Internal Medicine
    Stanford UniversityDoctor of MedicineMedicine

    Collapse Overview 
    Collapse Overview
    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.

    Collapse Research 
    Collapse Research Activities and Funding
    Interactions of Lymphocytes, Cytokines and Airway Cells
    NIH P50HL056385Sep 1, 1997 - Aug 31, 2006
    Role: Co-Investigator
    AMIDINE INHIBITORS OF LUNG MAST CELL TRYPTASE
    NIH R41HL057634Mar 1, 1997 - Feb 28, 1999
    Role: Principal Investigator
    HUMAN TRYPTASE GENE EXPRESSION
    NIH R01HL054774Jul 1, 1995 - Jun 30, 1999
    Role: Principal Investigator
    REGULATION FUNCTION OF AIRWAY PROTEASES
    NIH K08HL001736May 1, 1986 - Apr 30, 1991
    Role: Principal Investigator
    Evolving Microenvironments in Airway Inflammation
    NIH P01HL024136Jul 1, 1979 - Jun 30, 2010
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma. Cell. 2020 Jan 23; 180(2):406. Maun HR, Jackman JK, Choy DF, Loyet KM, Staton TL, Jia G, Dressen A, Hackney JA, Bremer M, Walters BT, Vij R, Chen X, Trivedi NN, Morando A, Lipari MT, Franke Y, Wu X, Zhang J, Liu J, Wu P, Chang D, Orozco LD, Christensen E, Wong M, Corpuz R, Hang JQ, Lutman J, Sukumaran S, Wu Y, Ubhayakar S, Liang X, Schwartz LB, Babina M, Woodruff PG, Fahy JV, Ahuja R, Caughey GH, Kusi A, Dennis MS, Eigenbrot C, Kirchhofer D, Austin CD, Wu LC, Koerber JT, Lee WP, Yaspan BL, Alatsis KR, Arron JR, Lazarus RA, Yi T. PMID: 31978350.
      View in: PubMed   Mentions:    Fields:    
    2. An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma. Cell. 2019 Oct 03; 179(2):417-431.e19. Maun HR, Jackman JK, Choy DF, Loyet KM, Staton TL, Jia G, Dressen A, Hackney JA, Bremer M, Walters BT, Vij R, Chen X, Trivedi NN, Morando A, Lipari MT, Franke Y, Wu X, Zhang J, Liu J, Wu P, Chang D, Orozco LD, Christensen E, Wong M, Corpuz R, Hang JQ, Lutman J, Sukumaran S, Wu Y, Ubhayakar S, Liang X, Schwartz LB, Babina M, Woodruff PG, Fahy JV, Ahuja R, Caughey GH, Kusi A, Dennis MS, Eigenbrot C, Kirchhofer D, Austin CD, Wu LC, Koerber JT, Lee WP, Yaspan BL, Alatsis KR, Arron JR, Lazarus RA, Yi T. PMID: 31585081.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimalsCells
    3. Therapeutic targeting of cathepsin C: from pathophysiology to treatment. Pharmacol Ther. 2018 10; 190:202-236. Korkmaz B, Caughey GH, Chapple I, Gauthier F, Hirschfeld J, Jenne DE, Kettritz R, Lalmanach G, Lamort AS, Lauritzen C, L?gowska M, Lesner A, Marchand-Adam S, McKaig SJ, Moss C, Pedersen J, Roberts H, Schreiber A, Seren S, Thakker NS. PMID: 29842917.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansAnimals
    4. A shocking diagnosis. J Hosp Med. 2017 02; 12(2):104-108. PMID: 28182807.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    5. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016 12; 48(12):1564-1569. PMID: 27749843.
      View in: PubMed   Mentions: 22     Fields:    Translation:Humans
    6. Cathepsin L Helps to Defend Mice from Infection with Influenza A. PLoS One. 2016; 11(10):e0164501. PMID: 27716790.
      View in: PubMed   Mentions: 3     Fields:    Translation:AnimalsCells
    7. Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts. Transplantation. 2016 10; 100(10):2090-8. PMID: 27077597.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansCells
    8. Divergent Inhibitor Susceptibility among Airway Lumen-Accessible Tryptic Proteases. PLoS One. 2015; 10(10):e0141169. PMID: 26485396.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansCells
    9. Mast cell proteases as pharmacological targets. Eur J Pharmacol. 2016 May 05; 778:44-55. PMID: 25958181.
      View in: PubMed   Mentions: 30     Fields:    Translation:HumansAnimalsCells
    10. Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux. PLoS One. 2015; 10(5):e0125797. PMID: 25938594.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    11. Mast cells present protrusions into blood vessels upon tracheal allergen challenge in mice. PLoS One. 2015; 10(3):e0118513. PMID: 25789765.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    12. Mast cells in a murine lung ischemia-reperfusion model of primary graft dysfunction. Respir Res. 2014 Aug 13; 15:95. PMID: 25115556.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimalsCells
    13. Dipeptidyl peptidase I controls survival from Klebsiella pneumoniae lung infection by processing surfactant protein D. Biochem Biophys Res Commun. 2014 Jul 18; 450(1):818-823. PMID: 24955853.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    14. 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. PMID: 23600672.
      View in: PubMed   Mentions: 6     Fields:    Translation:AnimalsCells
    15. 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. PMID: 23690397.
      View in: PubMed   Mentions: 33     Fields:    Translation:AnimalsCells
    16. 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. PMID: 23447538.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansAnimalsCells
    17. Association of large-airway lymphocytic bronchitis with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2013 Feb 15; 187(4):417-23. PMID: 23239157.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansCells
    18. Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells. . 2012 Jul; 303(2):L97-106. PMID: 22582115.
      View in: PubMed   Mentions:
    19. The avß6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells. J Clin Invest. 2012 Feb; 122(2):748-58. PMID: 22232213.
      View in: PubMed   Mentions: 31     Fields:    Translation:HumansAnimalsCells
    20. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice. PLoS One. 2011; 6(11):e27564. PMID: 22110673.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    21. Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa. J Leukoc Biol. 2012 Feb; 91(2):275-84. PMID: 22075928.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    22. Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol. 2011; 716:212-34. Caughey GH. PMID: 21713659.
      View in: PubMed   Mentions: 39     Fields:    Translation:HumansAnimalsCells
    23. How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution. J Immunol. 2010 Nov 01; 185(9):5360-8. Raymond WW, Trivedi NN, Makarova A, Ray M, Craik CS, Caughey GH. PMID: 20889553.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
    24. 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. Dougherty RH, Sidhu SS, Raman K, Solon M, Solberg OD, Caughey GH, Woodruff PG, Fahy JV. PMID: 20451039.
      View in: PubMed   Mentions: 72     Fields:    Translation:HumansCells
    25. Mast cell peptidases: chameleons of innate immunity and host defense. Am J Respir Cell Mol Biol. 2010 Mar; 42(3):257-67. Trivedi NN, Caughey GH. PMID: 19933375.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansAnimalsCells
    26. 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. Trivedi NN, Tamraz B, Chu C, Kwok PY, Caughey GH. PMID: 19748655.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansCells
    27. 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 01; 180(3):203-10. Innes AL, Carrington SD, Thornton DJ, Kirkham S, Rousseau K, Dougherty RH, Raymond WW, Caughey GH, Muller SJ, Fahy JV. PMID: 19423716.
      View in: PubMed   Mentions: 27     Fields:    Translation:Humans
    28. Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activity. J Immunol. 2009 May 01; 182(9):5770-7. Raymond WW, Su S, Makarova A, Wilson TM, Carter MC, Metcalfe DD, Caughey GH. PMID: 19380825.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansCells
    29. Guinea pig chymase is leucine-specific: a novel example of functional plasticity in the chymase/granzyme family of serine peptidases. J Biol Chem. 2008 May 16; 283(20):13943-51. Caughey GH, Beauchamp J, Schlatter D, Raymond WW, Trivedi NN, Banner D, Mauser H, Fingerle J. PMID: 18353771.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansAnimalsCells
    30. Chimerism, point mutation, and truncation dramatically transformed mast cell delta-tryptases during primate evolution. J Allergy Clin Immunol. 2008 May; 121(5):1262-8. Trivedi NN, Raymond WW, Caughey GH. PMID: 18325577.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansAnimalsCells
    31. Mast cell alpha and beta tryptases changed rapidly during primate speciation and evolved from gamma-like transmembrane peptidases in ancestral vertebrates. J Immunol. 2007 Nov 01; 179(9):6072-9. Trivedi NN, Tong Q, Raman K, Bhagwandin VJ, Caughey GH. PMID: 17947681.
      View in: PubMed   Mentions: 12     Fields:    Translation:HumansAnimalsCells
    32. Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev. 2007 Jun; 217:141-54. Caughey GH. PMID: 17498057.
      View in: PubMed   Mentions: 111     Fields:    Translation:HumansAnimalsCells
    33. Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels. Clin Immunol. 2007 Jun; 123(3):268-71. Akin C, Soto D, Brittain E, Chhabra A, Schwartz LB, Caughey GH, Metcalfe DD. PMID: 17449330.
      View in: PubMed   Mentions: 10     Fields:    Translation:Humans
    34. Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritis. Gastroenterology. 2007 Jun; 132(7):2422-37. Cottrell GS, Amadesi S, Pikios S, Camerer E, Willardsen JA, Murphy BR, Caughey GH, Wolters PJ, Coughlin SR, Peterson A, Knecht W, Pothoulakis C, Bunnett NW, Grady EF. PMID: 17570216.
      View in: PubMed   Mentions: 16     Fields:    Translation:AnimalsCells
    35. Regulation of the epithelial Na+ channel by peptidases. Curr Top Dev Biol. 2007; 78:23-46. Planès C, Caughey GH. PMID: 17338914.
      View in: PubMed   Mentions: 39     Fields:    Translation:HumansAnimals
    36. Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. J Exp Med. 2006 Dec 25; 203(13):2907-17. Xu X, Zhang D, Zhang H, Wolters PJ, Killeen NP, Sullivan BM, Locksley RM, Lowell CA, Caughey GH. PMID: 17158962.
      View in: PubMed   Mentions: 30     Fields:    Translation:AnimalsCells
    37. A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense. Curr Respir Med Rev. 2006 Aug; 2(39):263-277. Caughey GH. PMID: 18516248.
      View in: PubMed   Mentions:
    38. Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in mice. Biol Chem. 2006 Aug; 387(8):1143-6. Mallen-St Clair J, Shi GP, Sutherland RE, Chapman HA, Caughey GH, Wolters PJ. PMID: 16895486.
      View in: PubMed   Mentions: 10     Fields:    Translation:AnimalsCells
    39. Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor. . 2006 Dec; 291(6):C1258-70. Verghese GM, Gutknecht MF, Caughey GH. PMID: 16822939.
      View in: PubMed   Mentions:
    40. Tryptase genetics and anaphylaxis. J Allergy Clin Immunol. 2006 Jun; 117(6):1411-4. Caughey GH. PMID: 16751005.
      View in: PubMed   Mentions: 24     Fields:    Translation:HumansAnimals
    41. Mast cell and neutrophil peptidases attack an inactivation segment in hepatocyte growth factor to generate NK4-like antagonists. J Biol Chem. 2006 Jan 20; 281(3):1489-94. Raymond WW, Cruz AC, Caughey GH. PMID: 16303761.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansAnimalsCells
    42. Mast cells protect mice from Mycoplasma pneumonia. Am J Respir Crit Care Med. 2006 Jan 15; 173(2):219-25. Xu X, Zhang D, Lyubynska N, Wolters PJ, Killeen NP, Baluk P, McDonald DM, Hawgood S, Caughey GH. PMID: 16210667.
      View in: PubMed   Mentions: 32     Fields:    Translation:AnimalsCells
    43. Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens. J Heart Lung Transplant. 2005 Aug; 24(8):1055-66. Xu X, Golden JA, Dolganov G, Jones KD, Donnelly S, Weaver T, Caughey GH. PMID: 16102441.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansCells
    44. Mastin is a gelatinolytic mast cell peptidase resembling a mini-proteasome. Arch Biochem Biophys. 2005 Mar 15; 435(2):311-22. Raymond WW, Sommerhoff CP, Caughey GH. PMID: 15708374.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansAnimalsCells
    45. Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts. J Pathol. 2005 Jan; 205(1):102-11. Somasundaram P, Ren G, Nagar H, Kraemer D, Mendoza L, Michael LH, Caughey GH, Entman ML, Frangogiannis NG. PMID: 15586361.
      View in: PubMed   Mentions: 27     Fields:    Translation:AnimalsCells
    46. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line. . 2004 Nov; 287(5):L928-35. Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH. PMID: 15246975.
      View in: PubMed   Mentions:
    47. Matrix metalloproteinase-2 and -9 expression increases in Mycoplasma-infected airways but is not required for microvascular remodeling. . 2004 Aug; 287(2):L307-17. Baluk P, Raymond WW, Ator E, Coussens LM, McDonald DM, Caughey GH. PMID: 15075248.
      View in: PubMed   Mentions:
    48. Mast cell dipeptidyl peptidase I mediates survival from sepsis. J Clin Invest. 2004 Feb; 113(4):628-34. Mallen-St Clair J, Pham CT, Villalta SA, Caughey GH, Wolters PJ. PMID: 14966572.
      View in: PubMed   Mentions: 59     Fields:    Translation:AnimalsCells
    49. Mast cell cathepsins C and S control levels of carboxypeptidase A and the chymase, mouse mast cell protease 5. Biol Chem. 2003 Oct-Nov; 384(10-11):1527-31. Henningsson F, Wolters P, Chapman HA, Caughey GH, Pejler G. PMID: 14669996.
      View in: PubMed   Mentions: 11     Fields:    Translation:AnimalsCells
    50. Mouse prostasin gene structure, promoter analysis, and restricted expression in lung and kidney. Am J Respir Cell Mol Biol. 2004 Apr; 30(4):519-29. Verghese GM, Tong ZY, Bhagwandin V, Caughey GH. PMID: 12959947.
      View in: PubMed   Mentions: 9     Fields:    Translation:AnimalsCells
    51. Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site. J Biol Chem. 2003 Sep 05; 278(36):34517-24. Raymond WW, Ruggles SW, Craik CS, Caughey GH. PMID: 12815038.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansCells
    52. Structure of human pro-chymase: a model for the activating transition of granule-associated proteases. Biochemistry. 2003 Mar 11; 42(9):2616-24. Reiling KK, Krucinski J, Miercke LJ, Raymond WW, Caughey GH, Stroud RM. PMID: 12614156.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansCells
    53. Building a better heparin. Am J Respir Cell Mol Biol. 2003 Feb; 28(2):129-32. Caughey GH. PMID: 12540478.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimals
    54. Structure and activity of human pancreasin, a novel tryptic serine peptidase expressed primarily by the pancreas. J Biol Chem. 2003 Jan 31; 278(5):3363-71. Bhagwandin VJ, Hau LW, Mallen-St Clair J, Wolters PJ, Caughey GH. PMID: 12441343.
      View in: PubMed   Mentions: 12     Fields:    Translation:HumansAnimalsCells
    55. New developments in the genetics and activation of mast cell proteases. Mol Immunol. 2002 Sep; 38(16-18):1353-7. Caughey GH. PMID: 12217407.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansAnimalsCells
    56. Lys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymase. Biochim Biophys Acta. 2002 Apr 29; 1596(2):346-56. Muilenburg DJ, Raymond WW, Wolters PJ, Caughey GH. PMID: 12007614.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansAnimalsCells
    57. Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions. . 2002 Feb; 282(2):L197-206. Brown JK, Jones CA, Rooney LA, Caughey GH, Hall IP. PMID: 11792624.
      View in: PubMed   Mentions:
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