American College of Veterinary Pathologists
American Veterinary Medical Association
American Society for Microbiology
American Association of Veterinary Laboratory Diagnosticians
Conference of Research Workers in Animal Diseases
Department of Biomedical Sciences
Department of Pathology and Laboratory Medicine
Weill Cornell Medical College
Graduate Field of Comparative Biomedical Sciences
Graduate Field of Immunology
VTMED550, Animal Health & Disease Part I
Small Animal Gastrointestinal Pathology
VTMED571, Pathology Clinical Rotation
Education and Training
1982-86 Ph.D., Comparative Pathology
School of Veterinary Medicine, University of California-Davis
Advisor: Dr. Bennie I. Osburn
1980-82 Residency, Veterinary Anatomic Pathology
School of Veterinary Medicine, University of California-Davis
1976-80 Doctor of Veterinary Medicine
Faculty of Veterinary Medicine, University of Montreal
Saint-Hyacinthe, Quebec, Canada
1987 Anatomic Pathology
American College of Veterinary Pathologists
My laboratory focuses on understanding molecular mechanisms of host-parasite interactions and their relationship to susceptibility or resistance against enteric bacterial diseases, particularly within the framework of animal models of colitis.
Over the past 20 years, we have been conducting multi-institutional research together with an extensive network of collaborators in the United States, Australia, and Europe aimed at understanding the mechanism and biology of colitis associated with intestinal Brachyspira spirochete bacteria. Our work has focused primarily on Brachyspira pilosicoli, the cause of colonic spirochetosis (CS), an infection restricted to the large intestine of a broad range of hosts including humans and non-human primates, pigs, dogs, domestic poultry, and wildlife species. Recently, we have shown by in situ analysis studies that CS in non-human primates is identical to the disease found in humans, and consists of a polymicrobial epithelial biofilm composed of the pathogenic intestinal spirochetes Brachyspira pilosicoli and Brachyspira aalborgi together with certain enterohepatic Helicobacter species (EHS).
Presently, we seek to extend our observations to (i) uncover the natural history and biology of Brachyspira and EHS polymicrobial infections in various hosts, (ii) define the genomic diversity, population structure, and zoonotic potential of Brachyspira pilosicoli isolated from animal and environmental sources, and (iii) define the role of cytolethal distending toxin, a virulence factor found in EHS and several other related enteric bacterial pathogens including Campylobacter species associated with foodborne bacterial illnesses worldwide.
Given the broad range of host species where Brachyspira pilosicoli is found intimately adherent along the colonic epithelium together with EHS, we hypothesize that cross-talk between these bacteria leads to coordinate expression of genes involved in colonization and breakdown of colonic mucosal epithelial barrier function. We anticipate that this host-polymicrobial pathogen interaction model system will uncover novel and important mechanisms of colonic mucosal inflammatory and immune activation relevant to understanding the pathogenesis of inflammatory bowel disease.
Animal and cultured cell infection models and advanced microscopy
Fluorescent cytometry and laser scanning confocal microscopy for assessment of (i) bacterial adherence, invasion, and cytotoxicity in cultured human and animal intestinal epithelial cells, (ii) bacterial uptake and intracellular trafficking in human monocytic and mouse macrophage cells, (iii) analysis of lymphocyte subsets, (iv) stable and transient protein expression in eukaryotic cell lines, and (v) fluorescent in situ hybridization (FISH) of bacterial 16S and 23S rRNA genes. Light, transmission, scanning electron microscopy, and laser capture microdissection of tissues taken from spontaneous and experimentally-induced enteric diseases in animal models of human diseases.
Microbial molecular biology and immunology
Aerobic, microaerobic, and anaerobic bacterial culture and isolation from diagnostic specimens, bacterial gene-specific amplification by PCR assays, phylogenetic sequence analysis, bacterial protein fractionation and amino acid sequencing, recombinant fusion-protein overexpression/purification, production of antibodies to purified and synthetic peptide conjugates, ELISA and Western blot analyses, colorimetric bacterial nuclease and protease assays, cytokine quantitation by bead-array flow cytometry, immunohistochemical staining of pathogenic bacteria and host immune system components, and fluorescent activated cell sorting.
Selected Peer-reviewed Publications (from a total of 64)
- Navarathna DH, Nickerson KW, Duhamel GE, Jerrels TR, Petro TM 2007. Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model. Infect Immun 75:4006-4011.
- Navarathna DHMLP, Hornby JM, Krishnan N, Parkhurst A, Duhamel GE, Nickerson KW. 2007. Effect of farnesol on a mouse model of systemic candidiasis, determined by use of a DPP3 knockout mutant of Candida albicans. Infect Immun 75:1609-1618.
- Carvajal A, De Arriba ML, Rodriguez H, Vidal AB, Duhamel GE, Rubio P. 2006. Prevalence of Brachyspira species in pigs with diarrhoea in Spain. Vet Rec 158:700-701.
- Shivaprasad HL, Duhamel GE. 2005. Cecal spirochetosis caused by Brachyspira pilosicoli in commercial turkeys. Avian Dis 49:609-613.
- Navarathna DHMLP, Hornby JM, Hoerrmann N, Parkhurst AM, Duhamel GE, Nickerson KW. 2005. Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis. J Antimicrob Chemother 56:1156-1159.
- Dassanayake RP, Griep MA, Duhamel GE. 2005. The cytolethal distending toxin B sub-unit of Helicobacter hepaticus is a Ca2+- and Mg2+-dependent neutral nuclease. FEMS Microbiol Lett 251:219-225.
- Dassanayake RP, Zhou Y, Hinkley S, Stryker CJ, Plauche G, Borda JT, Sestak K, Duhamel GE. 2005. Characterization of cytolethal distending toxin of Campylobacter species isolated from captive macaque monkeys. J Clin Microbiol 43:641-649.
- De Cock HEV, Marks SL, Stacy BA, Zabka T, Burkitt J, Lu G, Steffen DJ, Duhamel GE. 2004. Ileocolitis associated with Anaerobiospirillum in cats. J Clin Microbiol 42:2752-2758.
- Johansson KE, Duhamel GE, Bergsjö B, Engvall EO, Persson M, Pettersson B, Fellström C. 2004. Identification of three clusters of canine intestinal spirochaetes by biochemical and 16S rDNA sequence analysis. J Med Microbiol 53:345-350.
- Dassanayake RP, Caceres NE, Sarath G, Duhamel GE. 2004. Biochemical properties of membrane-associated proteases of Brachyspira pilosicoli isolated from humans with intestinal disorders. J Med Microbiol 53:319-323.
- Duhamel GE, Stryker CJ, Lu G, Wong VJ Tarara RP. 2003. Colonic spirochetosis of colony-raised rhesus macaques associated with Brachyspira and Helicobacter. Anaerobe 9:45-55.
- Duhamel GE. 2001. Comparative pathology and pathogenesis of naturally acquired and experimentally induced colonic spirochetosis. Anim Health Res Rev 2:3-17.
- Zhang P, Cheng X, Duhamel GE. 2000. Cloning and DNA sequence analysis of an immunogenic glucose/galactose MglB lipoprotein homologue from Brachyspira pilosicoli, the agent of colonic spirochetosis. Infect Immun 68:4559-4565.
- Barcellos DESN, Mathiesen MR, de Uzeda M, Kader IITA, Duhamel GE. 2000. Prevalence of Brachyspira species isolated from diarrhoeic pigs in Brazil. Vet Rec 146: 398-403.
- Klein EC, Gebhart CJ, Duhamel GE. 1999. Fatal outbreaks of proliferative enteropathy caused by Lawsonia intracellularis in young colony-raised rhesus macaques. J Med Primatol 28:11-18.
- Muniappa N, Ramanathan MR, Tarara RP, Westerman RB, Mathiesen MR, Duhamel GE. 1998. Attachment of human and rhesus Serpulina pilosicoli to cultured cells and comparison with a chick infection model. J Spirochetal and Tick-borne Dis 5:44-53.
- Duhamel GE, Trott DJ, Muniappa N, Mathiesen MR, Tarasiuk K, Lee JI, Hampson DJ. 1998. Canine intestinal spirochetes consist of Serpulina pilosicoli and a newly identified group provisionally designated "Serpulina canis" sp. nov. J Clin Microbiol 36:2264-2270.
- Fisher LN, Mathiesen MR, Duhamel GE. 1997. Restriction fragment length polymorphism of the periplasmic flagellar flaA1 gene of Serpulina species. Clin Diagn Lab Immunol 4:681-686.
- Duhamel, GE, Elder RO, Muniappa N, Mathiesen MR, Wong VJ, Tarara RP. 1997. Colonic spirochetal infections in nonhuman primates that were associated with Brachyspira aalborgi, Serpulina pilosicoli, and unclassified flagellated bacteria. Clin Infect Dis 25(Supp 2):186-188.
- Fisher LN, Duhamel GE, Westerman RB, Mathiesen MR. 1997. Immunoblot reactivity of polyclonal and monoclonal antibodies with periplasmic flagellar FlaA1 and FlaB of porcine Serpulina species. Clin Diagn Lab Immunol 4:400-404.
- Muniappa N, Mathiesen MR, Duhamel GE. 1997. Laboratory identification and enteropathogenicity testing of Serpulina pilosicoli associated with porcine colonic spirochetosis. J Vet Diagn Invest 9:165-171.
- Muniappa N, Duhamel GE, Mathiesen MR, Bargar TW. 1996. Light microscopic and ultrastructural changes in the ceca of chicks inoculated with human and canine Serpulina pilosicoli. Vet Pathol 33:542-550.
- Trott DJ, Stanton TB, Jensen NS, Duhamel GE, Johnson JL, Hampson DJ. 1996. Serpulina pilosicoli sp. nov., the agent of porcine intestinal spirochetosis. Intl J Syst Bacteriol 46:206-215.
- Duhamel GE, Muniappa N, Mathiesen MR, Johnson JL, Toth J, Elder RO, Doster AR. 1995. Certain canine weakly ß-hemolytic intestinal spirochetes are phenotypically and genotypically related to spirochetes associated with human and porcine intestinal spirochetosis. J Clin Microbiol 33:2212-2215.
Selected Chapters in Books (from a total of 7)
- Duhamel GE. Neonatal calf enteric disease vaccines. In: Large Animal Internal Medicine. 4th ed., Smith BP (ed). Mosby, Inc., St. Louis, Missouri, in press.
- Hampson DJ, Duhamel GE. 2006. Porcine colonic spirochetosis/Intestinal spirochetosis. In: Diseases of Swine. 9th ed. Straw BE, Zimmerman JJ, D'Allaire S, and Taylor DJ (eds). Blackwell Publishing Ltd, Ames, Iowa, pp. 755-767.
- Duhamel GE. 2001. Neonatal calf enteric disease vaccines. In: Large Animal Internal Medicine. 3rd ed., Smith BP (ed). Mosby, Inc., St. Louis, Missouri, pp.1423-1427.
- Moxley RA, Duhamel GE. 1999. Comparative pathology of enteric bacterial diseases of swine. In: Mechanisms in the Pathogenesis of Enteric Diseases. Paul PS, Francis DH, and Benfield D (eds.), Plenum Publishing Corp., Washington, D.C., Adv. Exp. Med. Biol. 473:83-101.
- Duhamel GE. 1997. Intestinal spirochaetosis in non-production animals. In: Intestinal Spirochaetes in Domestic Animals and Humans. Hampson DJ, and Stanton TB (eds.). CAB International, Wallingford, England, pp. 301-320.