Prospective Students | Students | Faculty | Staff | Patients | Visitors | Alumni
 
 
Denver Skyline Image
Dr. Amura's Photo

 

Sean P. Colgan , PhD
Director of Mucosal Inflammation Program

Education

  • Undergraduate: BS, Microbiology, Colorado State University, Fort Collins, CO
  • Graduate: MS, Experimental Pathology, Colorado State University, Fort Collins, CO
    • PhD, Experimental Pathology, Colorado State University, Fort Collins, CO
  • Research Fellowship: Harvard Medical School

Honors and Awards

  • 1994 - Society of Leukocyte Biology: Young Investigator Award
  • 1999 - Mark and Diane Goldman and Family Research Scholar
  • 1999 - Designated Lecture, Physiological Society, Newcastle, UK
  • 2006 - Honorary M.A.: Harvard University, Cambridge, MA
  • 2008 - United of Colorado Outstanding PhD Research and Teaching Award

Faculty Appointments

  • 1994 - Instructor of Anaesthesiology, Harvard Medical School
  • 1994 - 1999 - Assistant Professor of Anaesthesiology, Harvard Medical School
  • 1999 - 2005 - Associate Professor of Anaesthesiology, Harvard Medical School
  • 2005 - present - Professor of Anaesthesiology, Harvard Medical School
  • 2006 - present - Kern Professor of Medicine, University of Colorado Denver
  • 2006 - present - Director, Mucosal Inflammation Program, University of Colorado Denver

Committees and Responsibilities

  • 2007-2010 Member, General Medicine and Pathobiology (GMPB) study section, NIH National Institutes of Diabetes and Digestive and Kidney Diseases
  • 2006 - Member, CCFA Medical Advisory Committee, Rocky Mountain Region
  • 2008 - Chairman, External Advisory Committee, Colorado Center for AIDS Research
  • 2008 - Section Editor, Journal of Immunology

Research Interests

Studies from Dr. Colgan's laboratory are aimed at understanding how epithelial and endothelial cells coordinate inflammatory bowel disease.

  • 1) Leukocyte cell-cell interactions: The pathological hallmark of many mucosal diseases is the accumulation of inflammatory cells such as neutrophils, macrophages and lymphocytes. At present, the signals and events which elicit recruitment of leukocytes to mucosal sites is not fully understood. Ongoing studies are aimed at determining the cellular and acellular components which contribute to trafficking of leukocytes across cell surfaces such as the intestine during infectious and inflammatory events. Specifically, we have focused on defining epithelial adhesion molecules important in neutrophil-epithelial interactions, and how such interactions might be regulated by soluble mediators present in the tissue microenvironment (chemokines, cytokines, lipids). Understanding the basic mechanisms of these events provide the basis for development of specific therapies aimed at treating such inflammatory conditions.
  • 2) Regulation of epithelial structure/function during inflammation: Epithelial cells which line mucosal organs such as the lung and intestine provide a barrier and a conduit for vectoral fluid transport. Our laboratory has a particular interest in defining the regulation of structural features of epithelial cells (polarity, membrane ion channels, cytoskeletal elements) during inflammation. Recent studies, for example, indicate that during periods of modeled inflammation, epithelial cells lose many classic epithelial features (e.g. barrier function, ion secretion) and garner many qualities indicative of immune accessory cells (e.g. MHC class expression, chemokine/cytokine synthesis). This epithelial “phenotype switch” contributes to the pathophysiologic mechanisms of mucosal diseases such as inflammatory bowel disease (IBD) and cystic fibrosis, and current studies are directed at developing models to examine potential therapeutic approaches to treat such disorders.
  • 3) Transcriptional signaling by hypoxia during inflammation: Diminished oxygen tension (hypoxia) is a contributing factor to developmental pathways and to a number of disease processes, including inflammation. Basic mechanisms of eukaryotic oxygen sensing and the transcriptional profile of genes induced by cellular hypoxia are not fully elucidated. Current studies are aimed at understanding basic cellular signaling pathways which contribute to transcriptional regulation of gene expression by hypoxia. Specifically, we employ the use of differential mRNA display technologies to profile transcriptional regulation of eukaryotic genes during episodes of diminished oxygen tension. Such studies are aimed at understanding novel crosstalk pathways between different cell types, how such crosstalk may be important during episodes of inflammation, and strategies for development of putative therapeutics.

Representative Original Publications

  1. Canny G, Levy O, Furuta GT, Narravula S, Sisson RB, Serhan CN, Colgan SP. Lipid mediator induced expression of bactericidal / permeability-increasing protein (BPI) in human mucosal epithelia. Proc Nat Acad Sci (USA) 2002; 99:3902-7 (download pdf)
  2. Lawrence DW, Bruyninckx WJ, Louis NA, Lublin DM, Stahl GL, Parkos CA, Colgan SP. Anti-adhesive role of apical decay-accelerating factor (DAF, CD55) in human neutrophil transmigration across mucosal epithelia. J Exp Med 2003; 198:999-1010 (download pdf)
  3. Karhausen JK, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH: Epithelial HIF-1 is protective in murine experimental colitis. J Clin Invest 2004; 114:1107-1116. (download pdf)
  4. Thompson LF, Eltzschig HK, Ibla JC, Van de Wiele CJ, Resta R, Morote-Garcia JC, Colgan SP. Crucial role for ecto-5'-nucleotidase in vascular leak during hypoxia. J Exp Med 2004; 200:1395-1405. (download pdf)
  5. Louis NA, Hamilton KE, Kong T, Colgan SP. HIF-dependent induction of apical CD55 coordinates epithelial clearance of neutrophils. FASEB J 2005:19, 950-959. (download pdf)
  6. Khoury J, Ibla JC, Neish AS and Colgan SP. Anti-inflammatory adaptation to hypoxia through adenosine-mediated Cullin-1 deneddylation. J Clin Invest. 2007: 117: 703-711. (download pdf)
  7. Kong T, Scully M, CS Shelley, Colgan SP. Identification of Pur-alpha as a new hypoxia response factor responsible for coordinated induction of the beta-2 integrin family. J Immunol 2007: 179: 1934-1941. (download pdf)
  8. Campbell E, Louis NA, Tomassetti SE, Canny GO, Arita M, Serhan CN and Colgan SP. Resolvin E1 promotes mucosal surface clearance of neutrophils: A new paradigm for inflammatory resolution. FASEB J 2007: 21: 3162-3170.(download pdf)
  9. Robinson AM, Keely S, Karhausen J, Gerich ME, Furuta GT, Colgan SP. Mucosal protection by hypoxia-inducible factor (HIF) prolyl hydroxylation inhibition. Gastroenterol 2008:134: 145-155.(download pdf)

Representative Books and Reviews

  1. Canny G, Colgan SP. Themes Perspective: Adaptation to a microbial world: role of epithelial bactericidal/permeability-increasing protein (BPI). Am J Physiol (Gastrointest Liver Physiol) 2005;288:G593-G597. (download PDF)
  2. Karhausen J, Haase VH, Colgan SP. Inflammatory hypoxia: Role of hypoxia-inducible factor. Cell. Cycle 2005; 4: 256-258.
  3. Weismuller T, Eltzschig HK, Colgan SP. Dynamic purine signaling and metabolism during neutrophil-endothelial interactions. Purinergic Signalling 2005;1:229-239. (download PDF)
  4. Colgan SP, editor.  Cell-Cell Interactions. Methods in Molecular Biology. Humana Press. Totowa, NJ. 2006.
  5. Taylor CT, Colgan SP. Hypoxia and gastrointestinal disease. J Mol Med 2008: 85:1295-1300.
  6. Eltzschig HK, ManManus CF, Colgan SP. Neutrophils as sources of extracellular nuleotides: Functional consequences at the vascular interface. Trends Cardio Med 2008: 8:103-107.