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George Caughey, MD

TitleProfessor
SchoolUCSF School of Medicine
DepartmentMedicine
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
    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. 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
    2. 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 Dec; 48(12):1564-1569. PMID: 27749843.
      View in: PubMed
    3. 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
    4. 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 Oct; 100(10):2090-8. PMID: 27077597.
      View in: PubMed
    5. 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.
    6. 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].
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. Greenland JR, Jewell NP, Gottschall M, Trivedi NN, Kukreja J, Hays SR, Singer JP, Golden JA, Caughey G. Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection. Am J Transplant. 2014 Apr; 14(4):831-40. PMID: 24512389; PMCID: PMC4300200.
    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; PMCID: PMC2756746.
    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; PMCID: PMC1949411.
    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. Wolters PJ, Mallen-St Clair J, Lewis CC, Villalta SA, Baluk P, Erle DJ, Caughey G. Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient Kit(W-sh)/Kit(W-sh) sash mice. Clin Exp Allergy. 2005 Jan; 35(1):82-8. PMID: 15649271; PMCID: PMC2271075.
    45. 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
    46. 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
    47. 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.
    48. 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
    49. 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
    50. 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
    51. 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
    52. Caughey G. Building a better heparin. Am J Respir Cell Mol Biol. 2003 Feb; 28(2):129-32. PMID: 12540478.
      View in: PubMed
    53. 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
    54. 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
    55. Soto D, Malmsten C, Blount JL, Muilenburg DJ, Caughey G. Genetic deficiency of human mast cell alpha-tryptase. Clin Exp Allergy. 2002 Jul; 32(7):1000-6. PMID: 12100045.
      View in: PubMed
    56. 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
    57. 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
    58. Caughey G. Chairman's summary. Mechanisms of airway remodeling. Am J Respir Crit Care Med. 2001 Nov 15; 164(10 Pt 2):S26-7. PMID: 11734463.
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    59. Schmidlin F, Amadesi S, Vidil R, Trevisani M, Martinet N, Caughey G, Tognetto M, Cavallesco G, Mapp C, Geppetti P, Bunnett NW. Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle. Am J Respir Crit Care Med. 2001 Oct 01; 164(7):1276-81. PMID: 11673222.
      View in: PubMed
    60. Wolters PJ, Pham CT, Muilenburg DJ, Ley TJ, Caughey G. Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J Biol Chem. 2001 May 25; 276(21):18551-6. PMID: 11279033.
      View in: PubMed
    61. Frank BT, Rossall JC, Caughey G, Fang KC. Mast cell tissue inhibitor of metalloproteinase-1 is cleaved and inactivated extracellularly by alpha-chymase. J Immunol. 2001 Feb 15; 166(4):2783-92. PMID: 11160345.
      View in: PubMed
    62. Brown JK, Jones CA, Rooney LA, Caughey G. Mast cell tryptase activates extracellular-regulated kinases (p44/p42) in airway smooth-muscle cells: importance of proteolytic events, time course, and role in mediating mitogenesis. Am J Respir Cell Mol Biol. 2001 Feb; 24(2):146-54. PMID: 11159048.
      View in: PubMed
    63. Caughey G, Raymond WW, Wolters PJ. Angiotensin II generation by mast cell alpha- and beta-chymases. Biochim Biophys Acta. 2000 Jul 14; 1480(1-2):245-57. PMID: 10899625.
      View in: PubMed
    64. Caughey G, Raymond WW, Blount JL, Hau LW, Pallaoro M, Wolters PJ, Verghese GM. Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families. J Immunol. 2000 Jun 15; 164(12):6566-75. PMID: 10843716.
      View in: PubMed
    65. Wolters PJ, Laig-Webster M, Caughey G. Dipeptidyl peptidase I cleaves matrix-associated proteins and is expressed mainly by mast cells in normal dog airways. Am J Respir Cell Mol Biol. 2000 Feb; 22(2):183-90. PMID: 10657939.
      View in: PubMed
    66. Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, Trevisani M, Hollenberg MD, Wallace JL, Caughey G, Mitchell SE, Williams LM, Geppetti P, Mayer EA, Bunnett NW. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000 Feb; 6(2):151-8. PMID: 10655102.
      View in: PubMed
    67. Steinhoff M, Corvera CU, Thoma MS, Kong W, McAlpine BE, Caughey G, Ansel JC, Bunnett NW. Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase. Exp Dermatol. 1999 Aug; 8(4):282-94. PMID: 10439226.
      View in: PubMed
    68. Corvera CU, Déry O, McConalogue K, Gamp P, Thoma M, Al-Ani B, Caughey G, Hollenberg MD, Bunnett NW. Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2. J Physiol. 1999 Jun 15; 517 ( Pt 3):741-56. PMID: 10358115; PMCID: PMC2269379.
    69. Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, Caughey G, Hanahan D. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev. 1999 Jun 01; 13(11):1382-97. PMID: 10364156; PMCID: PMC316772.
    70. Fang KC, Wolters PJ, Steinhoff M, Bidgol A, Blount JL, Caughey G. Mast cell expression of gelatinases A and B is regulated by kit ligand and TGF-beta. J Immunol. 1999 May 01; 162(9):5528-35. PMID: 10228034.
      View in: PubMed
    71. Pallaoro M, Fejzo MS, Shayesteh L, Blount JL, Caughey G. Characterization of genes encoding known and novel human mast cell tryptases on chromosome 16p13.3. J Biol Chem. 1999 Feb 05; 274(6):3355-62. PMID: 9920877.
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    72. Ma Y, Longley BJ, Wang X, Blount JL, Langley K, Caughey G. Clustering of activating mutations in c-KIT's juxtamembrane coding region in canine mast cell neoplasms. J Invest Dermatol. 1999 Feb; 112(2):165-70. PMID: 9989791.
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    73. Liu H, Lazarus SC, Caughey G, Fahy JV. Neutrophil elastase and elastase-rich cystic fibrosis sputum degranulate human eosinophils in vitro. Am J Physiol. 1999 Jan; 276(1 Pt 1):L28-34. PMID: 9887052.
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    74. Caughey G, Raymond WW, Fang KC. Porcine origin of human sputum trypsin? Am J Physiol. 1998 Jul; 275(1 Pt 1):L200-2. PMID: 9688952.
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    75. Wolters PJ, Raymond WW, Blount JL, Caughey G. Regulated expression, processing, and secretion of dog mast cell dipeptidyl peptidase I. J Biol Chem. 1998 Jun 19; 273(25):15514-20. PMID: 9624139.
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    76. Suzuki H, Caughey G, Gao XP, Rubinstein I. Mast cell chymase-like protease(s) modulates Escherichia coli lipopolysaccharide-induced vasomotor dysfunction in skeletal muscle in vivo. J Pharmacol Exp Ther. 1998 Mar; 284(3):1156-64. PMID: 9495878.
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    77. Caughey G, Blount JL, Koerber KL, Kitamura M, Fang KC. Cloning and expression of the dog mast cell alpha-chymase gene. J Immunol. 1997 Nov 01; 159(9):4367-75. PMID: 9379034.
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    78. Auchampach JA, Jin X, Wan TC, Caughey G, Linden J. Canine mast cell adenosine receptors: cloning and expression of the A3 receptor and evidence that degranulation is mediated by the A2B receptor. Mol Pharmacol. 1997 Nov; 52(5):846-60. PMID: 9351976.
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    79. Fang KC, Raymond WW, Blount JL, Caughey G. Dog mast cell alpha-chymase activates progelatinase B by cleaving the Phe88-Gln89 and Phe91-Glu92 bonds of the catalytic domain. J Biol Chem. 1997 Oct 10; 272(41):25628-35. PMID: 9325284.
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    80. Corvera CU, Déry O, McConalogue K, Böhm SK, Khitin LM, Caughey G, Payan DG, Bunnett NW. Mast cell tryptase regulates rat colonic myocytes through proteinase-activated receptor 2. J Clin Invest. 1997 Sep 15; 100(6):1383-93. PMID: 9294103; PMCID: PMC508316.
    81. Caughey G. Of mites and men: trypsin-like proteases in the lungs. Am J Respir Cell Mol Biol. 1997 Jun; 16(6):621-8. PMID: 9191463.
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    82. Soong LB, Ganz T, Ellison A, Caughey G. Purification and characterization of defensins from cystic fibrosis sputum. Inflamm Res. 1997 Mar; 46(3):98-102. PMID: 9098722.
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    83. Johnson PR, Ammit AJ, Carlin SM, Armour CL, Caughey G, Black JL. Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus. Eur Respir J. 1997 Jan; 10(1):38-43. PMID: 9032489.
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    84. Sommerhoff CP, Fang KC, Nadel JA, Caughey G. Classical second messengers are not involved in proteinase-induced degranulation of airway gland cells. Am J Physiol. 1996 Nov; 271(5 Pt 1):L796-803. PMID: 8944723.
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    85. Fang KC, Raymond WW, Lazarus SC, Caughey G. Dog mastocytoma cells secrete a 92-kD gelatinase activated extracellularly by mast cell chymase. J Clin Invest. 1996 Apr 01; 97(7):1589-96. PMID: 8601622; PMCID: PMC507221.
    86. Caughey G. Mast cell tryptase: hoisted by its own petard? J Clin Invest. 1996 Feb 15; 97(4):895-6. PMID: 8613539; PMCID: PMC507131.
    87. Brown JK, Tyler CL, Jones CA, Ruoss SJ, Hartmann T, Caughey G. Tryptase, the dominant secretory granular protein in human mast cells, is a potent mitogen for cultured dog tracheal smooth muscle cells. Am J Respir Cell Mol Biol. 1995 Aug; 13(2):227-36. PMID: 7626290.
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    88. Raymond WW, Tam EK, Blount JL, Caughey G. Purification and characterization of dog mast cell protease-3, an oligomeric relative of tryptases. J Biol Chem. 1995 Jun 02; 270(22):13164-70. PMID: 7768912.
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    89. Brown JK, Jones CA, Tyler CL, Ruoss SJ, Hartmann T, Caughey G. Tryptase-induced mitogenesis in airway smooth muscle cells. Potency, mechanisms, and interactions with other mast cell mediators. Chest. 1995 Mar; 107(3 Suppl):95S-96S. PMID: 7875014.
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    90. Caughey G. Serine proteinases of mast cell and leukocyte granules. A league of their own. Am J Respir Crit Care Med. 1994 Dec; 150(6 Pt 2):S138-42. PMID: 7952649.
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    91. Hartmann T, Ruoss SJ, Caughey G. Modulation of thrombin and thrombin receptor peptide mitogenicity by human lung mast cell tryptase. Am J Physiol. 1994 Aug; 267(2 Pt 1):L113-9. PMID: 8074233.
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    92. Yezzi MJ, Hsieh IE, Caughey G. Mast cell and neutrophil expression of dog mast cell protease-3. A novel tryptase-related serine protease. J Immunol. 1994 Mar 15; 152(6):3064-72. PMID: 8144904.
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    93. Caughey G. Should alpha 1-antitrypsin-deficient patients with emphysema continue to receive alpha 1-antitrypsin after lung transplantation? J Heart Lung Transplant. 1993 Jul-Aug; 12(4):708-9. PMID: 8369332.
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    94. Caughey G, Schaumberg TH, Zerweck EH, Butterfield JH, Hanson RD, Silverman GA, Ley TJ. The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression. Genomics. 1993 Mar; 15(3):614-20. PMID: 8468056.
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    95. Caughey G, Raymond WW, Bacci E, Lombardy RJ, Tidwell RR. Bis(5-amidino-2-benzimidazolyl)methane and related amidines are potent, reversible inhibitors of mast cell tryptases. J Pharmacol Exp Ther. 1993 Feb; 264(2):676-82. PMID: 8437115.
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    96. Matin R, Tam EK, Nadel JA, Caughey G. Distribution of chymase-containing mast cells in human bronchi. J Histochem Cytochem. 1992 Jun; 40(6):781-6. PMID: 1588024.
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    97. Sommerhoff CP, Ruoss SJ, Caughey G. Mast cell proteoglycans modulate the secretagogue, proteoglycanase, and amidolytic activities of dog mast cell chymase. J Immunol. 1992 May 01; 148(9):2859-66. PMID: 1573274.
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    98. Hartmann T, Ruoss SJ, Raymond WW, Seuwen K, Caughey G. Human tryptase as a potent, cell-specific mitogen: role of signaling pathways in synergistic responses. Am J Physiol. 1992 May; 262(5 Pt 1):L528-34. PMID: 1590404.
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    99. Ruoss SJ, Gold WM, Caughey G. Mast cell exocytosis: evidence that granule proteoglycan processing is not coupled to degranulation. Biochem Biophys Res Commun. 1991 Aug 30; 179(1):140-6. PMID: 1909118.
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    100. Ruoss SJ, Hartmann T, Caughey G. Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Invest. 1991 Aug; 88(2):493-9. PMID: 1864960; PMCID: PMC295370.
    101. Caughey G, Zerweck EH, Vanderslice P. Structure, chromosomal assignment, and deduced amino acid sequence of a human gene for mast cell chymase. J Biol Chem. 1991 Jul 15; 266(20):12956-63. PMID: 2071582.
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    102. Caughey G. The structure and airway biology of mast cell proteinases. Am J Respir Cell Mol Biol. 1991 May; 4(5):387-94. PMID: 2021478.
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    103. Rubinstein I, Nadel JA, Graf PD, Caughey G. Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs. J Clin Invest. 1990 Aug; 86(2):555-9. PMID: 2384602; PMCID: PMC296760.
    104. Tam EK, Caughey G. Degradation of airway neuropeptides by human lung tryptase. Am J Respir Cell Mol Biol. 1990 Jul; 3(1):27-32. PMID: 1694672.
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    105. Caughey G, Raymond WW, Vanderslice P. Dog mast cell chymase: molecular cloning and characterization. Biochemistry. 1990 May 29; 29(21):5166-71. PMID: 2378872.
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    106. Vanderslice P, Ballinger SM, Tam EK, Goldstein SM, Craik CS, Caughey G. Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family. Proc Natl Acad Sci U S A. 1990 May; 87(10):3811-5. PMID: 2187193; PMCID: PMC53993.
    107. Tam EK, Franconi GM, Nadel JA, Caughey G. Protease inhibitors potentiate smooth muscle relaxation induced by vasoactive intestinal peptide in isolated human bronchi. Am J Respir Cell Mol Biol. 1990 May; 2(5):449-52. PMID: 2187492.
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    108. Sommerhoff CP, Nadel JA, Basbaum CB, Caughey G. Neutrophil elastase and cathepsin G stimulate secretion from cultured bovine airway gland serous cells. J Clin Invest. 1990 Mar; 85(3):682-9. PMID: 2107207; PMCID: PMC296483.
    109. Caughey G. Tryptase and chymase in dog mast cells. Monogr Allergy. 1990; 27:67-89. PMID: 2084538.
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    110. Pison U, Tam EK, Caughey G, Hawgood S. Proteolytic inactivation of dog lung surfactant-associated proteins by neutrophil elastase. Biochim Biophys Acta. 1989 Sep 15; 992(3):251-7. PMID: 2775786.
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    111. Caughey G. Roles of mast cell tryptase and chymase in airway function. Am J Physiol. 1989 Aug; 257(2 Pt 1):L39-46. PMID: 2669522.
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    112. Nadel JA, Caughey G. Roles of mast cell proteases in airways. Chest. 1989 Jun; 95(6):1328-30. PMID: 2656114.
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    113. Vanderslice P, Craik CS, Nadel JA, Caughey G. Molecular cloning of dog mast cell tryptase and a related protease: structural evidence of a unique mode of serine protease activation. Biochemistry. 1989 May 16; 28(10):4148-55. PMID: 2504277.
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    114. Sommerhoff CP, Caughey G, Finkbeiner WE, Lazarus SC, Basbaum CB, Nadel JA. Mast cell chymase. A potent secretagogue for airway gland serous cells. J Immunol. 1989 Apr 01; 142(7):2450-6. PMID: 2494259.
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    115. Franconi GM, Graf PD, Lazarus SC, Nadel JA, Caughey G. Mast cell tryptase and chymase reverse airway smooth muscle relaxation induced by vasoactive intestinal peptide in the ferret. J Pharmacol Exp Ther. 1989 Mar; 248(3):947-51. PMID: 2495355.
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    116. Sekizawa K, Caughey G, Lazarus SC, Gold WM, Nadel JA. Mast cell tryptase causes airway smooth muscle hyperresponsiveness in dogs. J Clin Invest. 1989 Jan; 83(1):175-9. PMID: 2642918; PMCID: PMC303658.
    117. Sigal E, Grunberger D, Craik CS, Caughey G, Nadel JA. Arachidonate 15-lipoxygenase from human leukocytes: purification and structural homology to other mammalian lipoxygenases. Adv Prostaglandin Thromboxane Leukot Res. 1989; 19:156-9. PMID: 2526462.
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    118. Forsberg LS, Lazarus SC, Seno N, DeVinney R, Caughey G, Gold WM. Dog mastocytoma proteoglycans: occurrence of heparin and oversulfated chondroitin sulfates, containing trisulfated disaccharides, in three cell lines. Biochim Biophys Acta. 1988 Dec 15; 967(3):416-28. PMID: 3143422.
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    119. Caughey G, Viro NF, Calonico LD, McDonald DM, Lazarus SC, Gold WM. Chymase and tryptase in dog mastocytoma cells: asynchronous expression as revealed by enzyme cytochemical staining. J Histochem Cytochem. 1988 Aug; 36(8):1053-60. PMID: 3134486.
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    120. Sigal E, Grunberger D, Craik CS, Caughey G, Nadel JA. Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. Purification and structural homology to other mammalian lipoxygenases. J Biol Chem. 1988 Apr 15; 263(11):5328-32. PMID: 3356688.
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    121. Caughey G, Lazarus SC, Viro NF, Gold WM, Nadel JA. Tryptase and chymase: comparison of extraction and release in two dog mastocytoma lines. Immunology. 1988 Feb; 63(2):339-44. PMID: 3127330; PMCID: PMC1454507.
    122. Caughey G, Viro NF, Lazarus SC, Nadel JA. Purification and characterization of dog mastocytoma chymase: identification of an octapeptide conserved in chymotryptic leukocyte proteinases. Biochim Biophys Acta. 1988 Jan 29; 952(2):142-9. PMID: 3122835.
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    123. Sigal E, Grunberger D, Cashman JR, Craik CS, Caughey G, Nadel JA. Arachidonate 15-lipoxygenase from human eosinophil-enriched leukocytes: partial purification and properties. Biochem Biophys Res Commun. 1988 Jan 15; 150(1):376-83. PMID: 3337718.
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    124. Caughey G, Leidig F, Viro NF, Nadel JA. Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. J Pharmacol Exp Ther. 1988 Jan; 244(1):133-7. PMID: 2447273.
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    125. Caughey G, Viro NF, Ramachandran J, Lazarus SC, Borson DB, Nadel JA. Dog mastocytoma tryptase: affinity purification, characterization, and amino-terminal sequence. Arch Biochem Biophys. 1987 Nov 01; 258(2):555-63. PMID: 3118812.
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    126. Borson DB, Corrales R, Varsano S, Gold M, Viro N, Caughey G, Ramachandran J, Nadel JA. Enkephalinase inhibitors potentiate substance P-induced secretion of 35SO4-macromolecules from ferret trachea. Exp Lung Res. 1987; 12(1):21-36. PMID: 2434322.
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    127. Varsano S, Basbaum CB, Forsberg LS, Borson DB, Caughey G, Nadel JA. Dog tracheal epithelial cells in culture synthesize sulfated macromolecular glycoconjugates and release them from the cell surface upon exposure to extracellular proteinases. Exp Lung Res. 1987; 13(2):157-84. PMID: 3311721.
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    128. Caughey G, Wong H, Gamsu G, Golden J. Nonbronchoscopic bronchoalveolar lavage for the diagnosis for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Chest. 1985 Nov; 88(5):659-62. PMID: 2996837.
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    129. Caughey G, Rice SA, Kosek JC, Mazze RI. Effect of phenytoin (DPH) treatment on methoxyflurane metabolism in rats. J Pharmacol Exp Ther. 1979 Aug; 210(2):180-5. PMID: 458627.
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