Research Interests

My laboratory focuses on understanding molecular mechanisms of host-parasite interactions and their relationship to susceptibility or resistance against diseases, particularly within the framework of enteric bacterial infections in animal models of human diseases.

Perspective

Over the past 30 years, I have been engaged in basic and applied biomedical research aimed at characterizing the molecular basis of microbial pathogenesis and host defense with practical applications to diagnosis and control of enteric diseases of animals and human beings. As a board-certified Diplomate of the American College of Veterinary Pathologists and a Professor of Anatomic Veterinary Pathology, I oversee a research program focused on microbial pathogenesis of enteropathogenic Campylobacter and Helicobacter bacterial species in humans and animals, including laboratory mice and non-human primates and polymicrobial infections caused by these pathogens together with the intestinal spirochete Brachyspira pilosicoli. Specifically, I am interested in defining molecular mechanisms of bacterial virulence and host-pathogen interactions in cultured cell and animal models, phenotypic and genotypic bases of microbial diversity, and functional genomics. For the past several years my research efforts have focused on mechanisms of a novel bacterial genotoxin cytolethal distending toxin (CDT)-induced DNA damage response (DDR) within the context of intestinal disease of human and animals. I also collaborate with a wide range of basic research scientists by providing pathology assessment of various laboratory mouse models primarily of intestinal diseases.

Current Investigations

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.

Major Techniques

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.

PhD, Comparative Pathology, School of Veterinary Medicine, University of California-Davis, 1986 (Advisor: Dr. Bennie I. Osburn)
Residency, Veterinary Anatomic Pathology, School of Veterinary Medicine, University of California-Davis, 1980-1982
1976-80 Doctor of Veterinary Medicine, University of Montreal, 1980

Cornell University
Professor
2007 – Present
College of Veterinary Medicine and NY Animal Health Diagnostic Center

University of Nebraska–Lincoln
Professor
1986 – 2006
Department of Veterinary & Biomedical Sciences
 

1. Ki67 Labeling Index of Neoplastic Epithelial Cells Differentiates Canine Acanthomatous Ameloblastoma from Oral Squamous Cell Carcinoma. Peralta S, Grenier JK, McCleary-Wheeler AL, Duhamel GE. J Comp Pathol. 2019 Aug:171:59-69. doi: 10.1016/j.jcpa.2019.08.001 Epub 2019 Sep 5. PMID: 31540626
2. Pathology in Practice. Ruby RE, Sokol S, Duhamel GE. J AM Vet Med Assoc. 2019 Sep 1;255(5):543-545. doi: 10.2460/javma.255.5.543. PMID: 31429658
3. Pathology in Practice. Demeter EA, Canales GM, Scrivani PV, Duhamel GE. J Am Vet Med Assoc. 2019 Jun 1;254(11):1287-1290. doi: 10.2460/javma.254.11.1287. PMID: 31067183
4. Ultra-frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma. Peralta S, McCleary-Wheeler AL, Duhamel GE, Heikinheimo K, Grenier JK. Vet Comp Oncol. 2019 Sep;17(3):439-445. doi: 10.1111/vco.12487. Epub 2019 Jun 13. PMID: 31041834
5. Neuroborreliosis in a horse with common variable immunodeficiency. Pecoraro HL, Felippe MJB, Miller AD, Divers TJ, Simpson KW, Guyer KM, Duhamel GE. J Vet Diagn Invest. 2019 Mar;31(2):241-245. doi: 10.1177/1040638718824146. Epub 2019 Jan 19. PMID: 30661472
6. Small Intestinal Lymphatic Hypoplasia in Three Dogs with Clinical Signs of Protein-losing Enteropathy. Malatos JM, Kurpios NA, Duhamel GE. J Comp Pathol. 2018 Apr;160:3-49. doi: 10.1016/j.jcpa.2018.02.005. Epub 2018 Apr 4. PMID: 29729720
7. The Typhoid Toxin Produced by the Nontyphoidal Salmonella enterica Serotype Javiana Is Required for Induction of a DNA Damage Response In Vitro and Systemic Spread In Vivo. Miller RA, Betteken MI, Guo X, Altier C, Duhamel GE, Wiedmann M. mBio. 2018 Mar 27;9(2):e00467-18. doi: 10.1128/mBio.00467-18. PMID: 29588404
8. Characterization of a Vesivirus Associated with an Outbreak of Acute Hemorrhagic Gastroenteritis in Domestic Dogs. Renshaw RW, Griffing J, Weisman J, Crofton LM, Laverack MA, Poston RP, Duhamel GE, Dubovi EJ. J Clin Microbiol. 2018 Apr 25:56(5):e01951-17. doi: 10.1128/JCM.01951-17. Print 2018 May. PMID: 29444830
9. Gastric Dilatation Associated with Gastric Colonization with Sarcina-Like Bacteria in a Cat with Chronic Enteritis. Im JY, Sokol S, Duhamel GE. J Am Anim Hosp Assoc. 2017 Nov/Dec;53(6):321-325. doi: 10.5326/JAAHA.MS-6503. Epub 2017 Sep 11. PMID: 28892423
10. First demonstration of equid gammaherpesviruses within the gastric mucosal epithelium of horses. Pennington MR, Cossic BGA, Perkins GA, Duffy C, Duhamel GE, Van de Walle GR. Virus Res. 2017 Oct 15;242:30-36. doi: 10.1016/j.viruses.2017.09.002. Epub 2017 Sep 18. PMID: 28870469

Browse PubMed for a complete listing of Dr. Duhamel's publications

Professional Affiliations
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

Academic Affiliations
Department of Biomedical Sciences
Graduate Field of Comparative Biomedical Sciences
Graduate Field of Immunology