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.

Research Funding

  • July 1, 1979 - March 31, 2015 - Evolving Microenvironments in Airway Inflammation, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: P01HL024136
  • September 1, 1997 - August 31, 2006 - Interactions of Lymphocytes, Cytokines and Airway Cells, Co-Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: P50HL056385
  • July 1, 1995 - June 30, 1999 - HUMAN TRYPTASE GENE EXPRESSION, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R01HL054774
  • March 1, 1997 - February 28, 1999 - AMIDINE INHIBITORS OF LUNG MAST CELL TRYPTASE, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R41HL057634

Education

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

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. 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 An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma.  View on PubMed
  2. 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 An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma.  View on PubMed
  3. 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 Therapeutic targeting of cathepsin C: from pathophysiology to treatment.  View on PubMed
  4. Prabhakaran A, Dhaliwal G, Schilf CR, Caughey GH, Pile J A shocking diagnosis.  View on PubMed
  5. 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 GH, Heller T, Metcalfe DD, Biesecker LG, Schwartz LB, Milner JD Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.  View on PubMed
  6. Xu X, Greenland JR, Gotts JE, Matthay MA, Caughey GH Cathepsin L Helps to Defend Mice from Infection with Influenza A.  View on PubMed
  7. 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 GH, Tang Q Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts.  View on PubMed
  8. Nimishakavi S, Raymond WW, Gruenert DC, Caughey GH Divergent Inhibitor Susceptibility among Airway Lumen-Accessible Tryptic Proteases.  View on PubMed
  9. Caughey GH Mast cell proteases as pharmacological targets.  View on PubMed
  10. 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.  View on PubMed
  11. 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.  View on PubMed
  12. 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.  View on PubMed
  13. 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.  View on PubMed
  14. 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.  View on PubMed
  15. 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.  View on PubMed
  16. 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.  View on PubMed
  17. 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.  View on PubMed
  18. 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.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

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