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Thomas Bugge, Ph.D.

Thomas Bugge, Ph.D.Senior Investigator
Chief, Proteases and Tissue Remodeling Section

BETHESDA MD 20892-4340

Phone: (301) 435-1840
Fax: (301) 402-0823

Biographical Sketch

Thomas H. Bugge received his Ph.D. from the European Molecular Biology Laboratory and the University of Copenhagen, Denmark in 1993. He performed postdoctoral studies at Childrens' Hospital Research Foundation, Cincinnati, Ohio and University of Copenhagen from 1993-1995. Dr. Bugge was a research leader at The Finsen Laboratory, Copenhagen, Denmark from 1995-1996 and Associate Professor of Pediatrics in the Division of Developmental Biology, University of Cincinnati from 1997-1999, before being appointed to his current position. Dr. Bugge’s current research focuses on understanding the role of pericellular proteolysis in pathological and physiological tissue remodeling processes, with an emphasis on determining its contribution to the development, regeneration, and malignant transformation of oral tissues. He has published over 150 peer-reviewed articles, reviews, and book chapters on these topics. Dr. Bugge has organized and co-organized several scientific meetings, including Gordon Conferences, served on editorial boards of scientific journals and as a member of multiple national and international study sections and other scientific advisory committees. Service within NIDCR includes chairing the Institutional Animal Care and Use and Animal Program Director Search Committee, and memberships on the Gene Targeting Facility Oversight, Animal Care Facility Oversight, and Promotion and Tenure Committees. NIH service includes membership on the Animal Research Advisory, NIH Investigative, Earl Stadtman Search's Cell Biology/Cell Signaling Committees, and ad hoc review for the NIH Central Tenure Committee.

Mentoring is an important aspect of Dr. Bugge's work. He has supervised and mentored numerous post-baccalaureate and graduate students, research fellows, and tenure-track investigators, many of whom are now playing leadership roles at institutions in the U.S. and abroad. Dr. Bugge has received several NIH and international awards for his research, mentoring, and service to the scientific community, including the International Society for Fibrinolysis and Proteolysis Prize 2012 for "Outstanding Contributions to the Field of Fibrinolysis, Thrombolysis and Proteolysis."

Research Interests/Scientific Focus

Vertebrate genomes contain genes encoding hundreds of proteolytic enzymes that act on the cell surface to regulate all aspects of life, but when inappropriately regulated, they also play a critical role in the development and progression of numerous important human diseases. The aim of Dr. Bugge's Section is to understand the biochemistry, biology, and pathology of cell surface proteolysis, with particular emphasis on determining its contribution to the development, regeneration, and malignant transformation of oral tissues. The Section combines an assortment of sophisticated techniques to achieve this aim, including mouse molecular genetics, advanced imaging procedures, genomics, and state-of-the-art biochemistry. Current projects include: a) The study of membrane-anchored serine proteases in epithelial development, homeostasis, and malignant transformation. b) Use of protease-activated bacterial cytotoxins for the treatment of solid tumors. c) Defining the mechanisms and functions of intracellular turnover of collagen.

Major achievements of the section in recent years include the identification and characterization of novel membrane-anchored serine proteases, defining the molecular targets for transmembrane serine protease inhibitors, uncovering a cell surface serine protease cascade required for development of stratified epithelium, discovery of a role of membrane proteases in epithelial tight junction formation, revealing a principal role of urokinase binding to its receptor in suppressing fibrin-associated chronic inflammation, elucidation of protease-mediated tumor-initiating signaling pathways, development with Steve Leppla, NIAID, of protease-activated bacterial cytoxins for tumor treatment and protease imaging, and the identification and functional characterization of a receptor responsible for the cellular uptake and lysosomal degradation of collagen.

Selected Publications

  1. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway Madsen DH, Leonard D, Masedunskas A, Moyer A, Jessen Jürgensen H, Peters DE, Amornphimoltham P, Selvaraj A, Yamada SS, Brenner DA, Burgdorf S, Engelholm LH, Behrendt N, Holmbeck K, Weigert R, and Bugge TH. J Cell Biol 2013 Sep 16;202(6):951-66. Epub 2013 Sep 9. PMID: 24019537 [PubMed - in process]
  2. Membrane-anchored serine proteases in vertebrate cell and developmental biology Szabo R, Bugge TH. Annu Rev Cell Dev Biol. 2011 Nov 10;27:213-35. Epub 2011 Jun 29. PubMed PMID: 21721945.
  3. c-Met-induced epithelial carcinogenesis is initiated by the serine protease matriptase Szabo R, Rasmussen AL, Moyer AB, Kosa P, Schafer JM, Molinolo AA, Gutkind JS, Bugge TH. Oncogene. 2011 Apr 28;30(17):2003-16. Epub 2011 Jan 10. PubMed PMID: 21217780; PubMed Central PMCID: PMC3084339.
  4. Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome Sales KU, Masedunskas A, Bey AL, Rasmussen AL, Weigert R, List K, Szabo R, Overbeek PA, Bugge TH. Nat Genet. 2010 Aug;42(8):676-83. Epub 2010 Jul 25. PubMed PMID: 20657595; PubMed Central PMCID: PMC3081165.
  5. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation Connolly BM, Choi EY, Gårdsvoll H, Bey AL, Currie BM, Chavakis T, Liu S, Molinolo A, Ploug M, Leppla SH, Bugge TH. Blood. 2010 Sep 2;116(9):1593-603. Epub 2010 May 13. PubMed PMID: 20466854; PubMed Central PMCID: PMC2938846.
  6. Epithelial integrity is maintained by a matriptase-dependent proteolytic pathway List K, Kosa P, Szabo R, Bey AL, Wang CB, Molinolo A, Bugge TH. Am J Pathol. 2009 Oct;175(4):1453-63. Epub 2009 Aug 28. PubMed PMID: 19717635; PubMed Central PMCID: PMC2751542.
  7. Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice Szabo R, Hobson JP, Christoph K, Kosa P, List K, Bugge TH. Development. 2009 Aug;136(15):2653-63. PubMed PMID: 19592578; PubMed Central PMCID: PMC2709071.
  8. Matriptase inhibition by hepatocyte growth factor activator inhibitor-1 is essential for placental development Szabo R, Molinolo A, List K, Bugge TH. Oncogene. 2007 Mar 8;26(11):1546-56. Epub 2006 Sep 18. PubMed PMID: 16983341.
  9. Evidence for a matriptase-prostasin proteolytic cascade regulating terminal epidermal differentiation Netzel-Arnett S, Currie BM, Szabo R, Lin CY, Chen LM, Chai KX, Antalis TM, Bugge TH, List K. J Biol Chem. 2006 Nov 3;281(44):32941-5. Epub 2006 Sep 15. PubMed PMID: 16980306
  10. Imaging specific cell-surface proteolytic activity in single living cells Hobson JP, Liu S, Rønø B, Leppla SH, Bugge TH. Nat Methods. 2006 Apr;3(4):259-61. PubMed PMID: 16554829.
  11. Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation List K, Szabo R, Molinolo A, Sriuranpong V, Redeye V, Murdock T, Burke B, Nielsen BS, Gutkind JS, Bugge TH. Genes Dev. 2005 Aug 15;19(16):1934-50. PubMed PMID: 16103220; PubMed Central PMCID: PMC1186192.
  12. Intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin Liu S, Redeye V, Kuremsky JG, Kuhnen M, Molinolo A, Bugge TH, Leppla SH. Nat Biotechnol. 2005 Jun;23(6):725-30. Epub 2005 May 15. PubMed PMID: 15895075; PubMed Central PMCID: PMC2405912.
  13. Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy Curino AC, Engelholm LH, Yamada SS, Holmbeck K, Lund LR, Molinolo AA, Behrendt N, Nielsen BS, Bugge TH. J Cell Biol. 2005 Jun 20;169(6):977-85. PubMed PMID: 15967816; PubMed Central PMCID: PMC2171632.
  14. Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1 List K, Szabo R, Wertz PW, Segre J, Haudenschild CC, Kim SY, Bugge TH. J Cell Biol. 2003 Nov 24;163(4):901-10. PubMed PMID: 14638864; PubMed Central PMCID: PMC2173680.
  15. uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion Engelholm LH, List K, Netzel-Arnett S, Cukierman E, Mitola DJ, Aaronson H, Kjøller L, Larsen JK, Yamada KM, Strickland DK, Holmbeck K, Danø K, Birkedal-Hansen H, Behrendt N, Bugge TH. J Cell Biol. 2003 Mar 31;160(7):1009-15. PubMed PMID: 12668656; PubMed Central PMCID: PMC2172772.
  16. Potent antitumor activity of a urokinase-activated engineered anthrax toxin
    Liu S, Aaronson H, Mitola DJ, Leppla SH, Bugge TH. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):657-62. Epub 2003 Jan 13. PubMed PMID: 12525700; PubMed Central PMCID: PMC141052.

Complete CV (PDF, 79KB)

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This page last updated: May 28, 2014