Loading...

George Caughey, MD

TitleProfessor Emeritus
InstitutionUniversity of California San Francisco
DepartmentMedicine
Address90 Medical Center Way
San Francisco CA 94143
Phone415-221-4810 ext. 6385
vCardDownload vCard

    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
    AMIDINE INHIBITORS OF LUNG MAST CELL TRYPTASE
    NIH/NHLBI R41HL057634Mar 1, 1997 - Feb 28, 1999
    Role: Principal Investigator
    Interactions of Lymphocytes, Cytokines and Airway Cells
    NIH/NHLBI P50HL056385Sep 30, 1996 - Aug 31, 2006
    Role: Co-Investigator
    HUMAN TRYPTASE GENE EXPRESSION
    NIH/NHLBI R01HL054774Jul 1, 1995 - Jun 30, 1999
    Role: Principal Investigator
    REGULATION FUNCTION OF AIRWAY PROTEASES
    NIH/NHLBI K08HL001736May 1, 1986 - Apr 30, 1991
    Role: Principal Investigator
    Evolving Microenvironments in Airway Inflammation
    NIH/NHLBI P01HL024136Jul 1, 1979 - Mar 31, 2015
    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.
    List All   |   Timeline
    1. Korkmaz B, Caughey G, Chapple I, Gauthier F, Hirschfeld J, Jenne DE, Kettritz R, Lalmanach G, Lamort AS, Lauritzen C, Legowska M, Lesner A, Marchand-Adam S, McKaig SJ, Moss C, Pedersen J, Roberts H, Schreiber A, Seren S, Thakkar NS. Therapeutic targeting of cathepsin C: from pathophysiology to treatment. Pharmacol Ther. 2018 May 26. PMID: 29842917.
      View in: PubMed
    2. Prabhakaran A, Dhaliwal G, Schilf CR, Caughey G, Pile J. A shocking diagnosis. J Hosp Med. 2017 Feb; 12(2):104-108. PMID: 28182807.
      View in: PubMed
    3. Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, Ho N, Zhao M, Liu Y, O'Connell MP, Trivedi NN, Nelson C, DiMaggio T, Jones N, Matthews H, Lewis KL, Oler AJ, Carlson RJ, Arkwright PD, Hong C, Agama S, Wilson TM, Tucker S, Zhang Y, McElwee JJ, Pao M, Glover SC, Rothenberg ME, Hohman RJ, Stone KD, Caughey G, Heller T, Metcalfe DD, Biesecker LG, Schwartz LB, Milner JD. 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
    4. Xu X, Greenland JR, Gotts JE, Matthay MA, Caughey G. Cathepsin L Helps to Defend Mice from Infection with Influenza A. PLoS One. 2016; 11(10):e0164501. PMID: 27716790.
      View in: PubMed
    5. Greenland JR, Wong CM, Ahuja R, Wang AS, Uchida C, Golden JA, Hays SR, Leard LE, Rajalingam R, Singer JP, Kukreja J, Wolters PJ, Caughey G, Tang Q. 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
    6. Nimishakavi S, Raymond WW, Gruenert DC, Caughey G. Divergent Inhibitor Susceptibility among Airway Lumen-Accessible Tryptic Proteases. PLoS One. 2015; 10(10):e0141169. PMID: 26485396; PMCID: PMC4612780.
    7. Caughey G. Mast cell proteases as pharmacological targets. Eur J Pharmacol. 2016 May 05; 778:44-55. PMID: 25958181; PMCID: PMC4636979 [Available on 05/05/17].
    8. Raymond WW, Xu X, Nimishakavi S, Le C, McDonald DM, Caughey G. Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux. PLoS One. 2015; 10(5):e0125797. PMID: 25938594; PMCID: PMC4418689.
    9. Bose O, Baluk P, Looney MR, Cheng LE, McDonald DM, Caughey G, Krummel MF. Mast cells present protrusions into blood vessels upon tracheal allergen challenge in mice. PLoS One. 2015; 10(3):e0118513. PMID: 25789765; PMCID: PMC4366375.
    10. Greenland JR, Xu X, Sayah DM, Liu FC, Jones KD, Looney MR, Caughey G. Mast cells in a murine lung ischemia-reperfusion model of primary graft dysfunction. Respir Res. 2014 Aug 13; 15:95. PMID: 25115556; PMCID: PMC4151192.
    11. Sutherland RE, Barry SS, Olsen JS, Salantes DB, Caughey G, 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):818-823. PMID: 24955853; PMCID: PMC4107110.
    12. Xu X, Greenland J, Baluk P, Adams A, Bose O, McDonald DM, Caughey G. 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; PMCID: PMC3824055.
    13. Chau JY, Tiffany CM, Nimishakavi S, Lawrence JA, Pakpour N, Mooney JP, Lokken KL, Caughey G, 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. PMID: 23690397; PMCID: PMC3811760.
    14. Raman K, Trivedi NN, Raymond WW, Ganesan R, Kirchhofer D, Verghese GM, Craik CS, Schneider EL, Nimishakavi S, Caughey G. 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; PMCID: PMC3624440.
    15. Greenland JR, Jones KD, Hays SR, Golden JA, Urisman A, Jewell NP, Caughey G, 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. PMID: 23239157; PMCID: PMC3603592.
    16. Nimishakavi S, Besprozvannaya M, Raymond WW, Craik CS, Gruenert DC, Caughey G. 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. PMID: 22582115; PMCID: PMC3404626.
    17. Sugimoto K, Kudo M, Sundaram A, Ren X, Huang K, Bernstein X, Wang Y, Raymond WW, Erle DJ, Abrink M, Caughey G, Huang X, Sheppard D. The avß6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells. J Clin Invest. 2012 Feb; 122(2):748-58. PMID: 22232213; PMCID: PMC3266785.
    18. Sutherland RE, Xu X, Kim SS, Seeley EJ, Caughey G, Wolters PJ. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice. PLoS One. 2011; 6(11):e27564. PMID: 22110673; PMCID: PMC3217977.
    19. Xu X, Zhang H, Song Y, Lynch SV, Lowell CA, Wiener-Kronish JP, Caughey G. Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa. J Leukoc Biol. 2012 Feb; 91(2):275-84. PMID: 22075928; PMCID: PMC3290427.
    20. Caughey G. Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol. 2011; 716:212-34. PMID: 21713659; PMCID: PMC3954859.
    21. Raymond WW, Trivedi NN, Makarova A, Ray M, Craik CS, Caughey G. 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. PMID: 20889553; PMCID: PMC3954857.
    22. Dougherty RH, Sidhu SS, Raman K, Solon M, Solberg OD, Caughey G, 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. PMID: 20451039; PMCID: PMC2918406.
    23. Trivedi NN, Caughey G. Mast cell peptidases: chameleons of innate immunity and host defense. Am J Respir Cell Mol Biol. 2010 Mar; 42(3):257-67. PMID: 19933375; PMCID: PMC2830402.
    24. Trivedi NN, Tamraz B, Chu C, Kwok PY, Caughey G. 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. PMID: 19748655; PMCID: PMC2783561.
    25. Innes AL, Carrington SD, Thornton DJ, Kirkham S, Rousseau K, Dougherty RH, Raymond WW, Caughey G, 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 01; 180(3):203-10. PMID: 19423716; PMCID: PMC2724713.
    26. Raymond WW, Su S, Makarova A, Wilson TM, Carter MC, Metcalfe DD, Caughey G. 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. PMID: 19380825.
      View in: PubMed
    27. Caughey G, Beauchamp J, Schlatter D, Raymond WW, Trivedi NN, Banner D, Mauser H, Fingerle J. 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. PMID: 18353771; PMCID: PMC2376239.
    28. Trivedi NN, Raymond WW, Caughey G. Chimerism, point mutation, and truncation dramatically transformed mast cell delta-tryptases during primate evolution. J Allergy Clin Immunol. 2008 May; 121(5):1262-8. PMID: 18325577.
      View in: PubMed
    29. Trivedi NN, Tong Q, Raman K, Bhagwandin VJ, Caughey G. 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. PMID: 17947681; PMCID: PMC2366170.
    30. Caughey G. Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev. 2007 Jun; 217:141-54. PMID: 17498057; PMCID: PMC2275918.
    31. Akin C, Soto D, Brittain E, Chhabra A, Schwartz LB, Caughey G, Metcalfe DD. Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels. Clin Immunol. 2007 Jun; 123(3):268-71. PMID: 17449330.
      View in: PubMed
    32. Cottrell GS, Amadesi S, Pikios S, Camerer E, Willardsen JA, Murphy BR, Caughey G, Wolters PJ, Coughlin SR, Peterson A, Knecht W, Pothoulakis C, Bunnett NW, Grady EF. Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritis. Gastroenterology. 2007 Jun; 132(7):2422-37. PMID: 17570216; PMCID: PMC2366898.
    33. Planès C, Caughey G. Regulation of the epithelial Na+ channel by peptidases. Curr Top Dev Biol. 2007; 78:23-46. PMID: 17338914; PMCID: PMC2276519.
    34. Xu X, Zhang D, Zhang H, Wolters PJ, Killeen NP, Sullivan BM, Locksley RM, Lowell CA, Caughey G. Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. J Exp Med. 2006 Dec 25; 203(13):2907-17. PMID: 17158962; PMCID: PMC2118183.
    35. Mallen-St Clair J, Shi GP, Sutherland RE, Chapman HA, Caughey G, Wolters PJ. 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. PMID: 16895486; PMCID: PMC2271110.
    36. Caughey G. A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense. Curr Respir Med Rev. 2006 Aug; 2(39):263-277. PMID: 18516248.
      View in: PubMed
    37. Verghese GM, Gutknecht MF, Caughey G. Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor. Am J Physiol Cell Physiol. 2006 Dec; 291(6):C1258-70. PMID: 16822939; PMCID: PMC2271112.
    38. Caughey G. Tryptase genetics and anaphylaxis. J Allergy Clin Immunol. 2006 Jun; 117(6):1411-4. PMID: 16751005; PMCID: PMC2271076.
    39. Raymond WW, Cruz AC, Caughey G. 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. PMID: 16303761; PMCID: PMC2271111.
    40. Xu X, Zhang D, Lyubynska N, Wolters PJ, Killeen NP, Baluk P, McDonald DM, Hawgood S, Caughey G. Mast cells protect mice from Mycoplasma pneumonia. Am J Respir Crit Care Med. 2006 Jan 15; 173(2):219-25. PMID: 16210667; PMCID: PMC2662990.
    41. Xu X, Golden JA, Dolganov G, Jones KD, Donnelly S, Weaver T, Caughey G. Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens. J Heart Lung Transplant. 2005 Aug; 24(8):1055-66. PMID: 16102441; PMCID: PMC2271113.
    42. Raymond WW, Sommerhoff CP, Caughey G. Mastin is a gelatinolytic mast cell peptidase resembling a mini-proteasome. Arch Biochem Biophys. 2005 Mar 15; 435(2):311-22. PMID: 15708374.
      View in: PubMed
    43. Somasundaram P, Ren G, Nagar H, Kraemer D, Mendoza L, Michael LH, Caughey G, Entman ML, Frangogiannis NG. Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts. J Pathol. 2005 Jan; 205(1):102-11. PMID: 15586361; PMCID: PMC2275298.
    44. Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey G. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol. 2004 Nov; 287(5):L928-35. PMID: 15246975.
      View in: PubMed
    45. Baluk P, Raymond WW, Ator E, Coussens LM, McDonald DM, Caughey G. Matrix metalloproteinase-2 and -9 expression increases in Mycoplasma-infected airways but is not required for microvascular remodeling. Am J Physiol Lung Cell Mol Physiol. 2004 Aug; 287(2):L307-17. PMID: 15075248.
      View in: PubMed
    46. Mallen-St Clair J, Pham CT, Villalta SA, Caughey G, Wolters PJ. Mast cell dipeptidyl peptidase I mediates survival from sepsis. J Clin Invest. 2004 Feb; 113(4):628-34. PMID: 14966572; PMCID: PMC338261.
    47. Henningsson F, Wolters P, Chapman HA, Caughey G, Pejler G. 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. PMID: 14669996.
      View in: PubMed
    48. Verghese GM, Tong ZY, Bhagwandin V, Caughey G. 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. PMID: 12959947.
      View in: PubMed
    49. Raymond WW, Ruggles SW, Craik CS, Caughey G. 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. PMID: 12815038.
      View in: PubMed
    50. Reiling KK, Krucinski J, Miercke LJ, Raymond WW, Caughey G, Stroud RM. Structure of human pro-chymase: a model for the activating transition of granule-associated proteases. Biochemistry. 2003 Mar 11; 42(9):2616-24. PMID: 12614156.
      View in: PubMed
    51. Caughey G. Building a better heparin. Am J Respir Cell Mol Biol. 2003 Feb; 28(2):129-32. PMID: 12540478.
      View in: PubMed
    52. Bhagwandin VJ, Hau LW, Mallen-St Clair J, Wolters PJ, Caughey G. 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. PMID: 12441343.
      View in: PubMed
    53. Caughey G. New developments in the genetics and activation of mast cell proteases. Mol Immunol. 2002 Sep; 38(16-18):1353-7. PMID: 12217407.
      View in: PubMed
    54. Muilenburg DJ, Raymond WW, Wolters PJ, Caughey G. Lys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymase. Biochim Biophys Acta. 2002 Apr 29; 1596(2):346-56. PMID: 12007614.
      View in: PubMed
    55. Brown JK, Jones CA, Rooney LA, Caughey G, Hall IP. Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions. Am J Physiol Lung Cell Mol Physiol. 2002 Feb; 282(2):L197-206. PMID: 11792624.
      View in: PubMed
    George's Networks
    Concepts
    Derived automatically from this person's publications.
    _
    Co-Authors
    People in Profiles who have published with this person.
    _
    Related Authors
    People who share related concepts with this person.
    _