About

Gerald Duhamel, DVM, PhD, DACVP, is a Professor of Anatomic Pathology at Cornell University College of Veterinary Medicine, where he is also affiliated with the Department of Biomedical and Translational Sciences and the Department of Population Medicine and Diagnostic Sciences. His research 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. Over the past 30 years, he has engaged in basic and applied biomedical research aimed at characterizing the molecular basis of microbial pathogenesis and host defense, with practical applications to the diagnosis and control of enteric diseases affecting animals and humans.

Research topics

• Biology
• Medicine
• Genetics
• Pathology
• Cancer research
• Sociology
• Anatomy
• Endocrinology
• Immunology
• Internal medicine

Selected publications

• Cervical suppurative fasciitis and sudden death in a 4-month-old Angus steer

  Journal of the American Veterinary Medical Association · 2026-04-17

  articleSenior author
  PublisherDOI

• Neuroepithelial reprogramming and ERBB vulnerability in canine acanthomatous ameloblastoma

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-05

  articleOpen access

  Abstract Canine acanthomatous ameloblastoma (CAA) is a locally invasive benign oral neoplasm that is difficult to distinguish from canine oral squamous cell carcinoma (COSCC) due to overlapping clinical, radiologic, and histologic features. Although both tumors exhibit MAPK pathway activation, their mutational landscapes are distinct. Furthermore, previous studies using bulk RNA sequencing (RNA-seq) have demonstrated pronounced differences in programs related to, among others, hypoxia, PI3K-AKT signaling, and cell proliferation. However, these bulk studies lacked the resolution to elucidate the cellular heterogeneity of CAA relative to COSCC. We therefore performed single-nucleus RNA-seq to define the cellular gene expression landscape of CAA, COSCC, and healthy gingiva. Across ∼205,000 nuclei, we identified major epithelial, immune, endothelial, and mesenchymal populations, as well as two epithelial subtypes uniquely enriched in CAA. The CAA-specific keratinocytes exhibited a neuronal-like expression program defined by synaptic regulators, KRAS-associated signaling pathways, and markedly elevated expression of PEG3, ERBB4, GABRB1, MAGI2 , and CASK . These findings were validated by bulk RNA-seq, qPCR, and immunohistochemistry, which demonstrated strong nuclear localization of PEG3 exclusively in CAA epithelium. A kinase inhibitor screen independently identified ERBB4 as a candidate therapeutic vulnerability, and pharmacologic inhibition with neratinib was effective. Together, these findings reveal a previously unrecognized neuroepithelial cell state that defines CAA, distinguishes it from COSCC, and reveals unique diagnostic and therapeutic signaling dependencies. Given the molecular and histopathologic parallels between CAA and human ameloblastoma, these data further position CAA as a naturally occurring comparative model for studying ameloblastoma biology and therapeutic vulnerabilities. Significance Statement Canine acanthomatous ameloblastoma (CAA) is a common locally aggressive oral neoplasm often misdiagnosed as canine oral squamous cell carcinoma (COSCC) due to overlapping clinical, radiologic, and histologic features. Using single-nucleus RNA sequencing of CAA, COSCC, and healthy gingiva, we resolve the microenvironment of these tumors and detect two epithelial subpopulations unique to CAA. These CAA-specific keratinocytes exhibit a neuroepithelial-like signature characterized by synaptic regulators, KRAS-associated signaling, and elevated PEG3 and ERBB4 expression. Functional kinase inhibitor screening of patient derived microtumor slices independently converged on ERBB4 as an effective therapeutic target. Together, our study provides a molecular framework for distinguishing CAA from COSCC and establishes a comparative oncology model with translational relevance to human ameloblastoma and other ERBB-driven epithelial neoplasms.

  PublisherDOI

• The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma

  Scientific Reports · 2025-02-27 · 8 citations

  articleOpen access

  Oral tumors are relatively common in dogs, and canine oral squamous cell carcinoma (COSCC) is the most prevalent oral malignancy of epithelial origin. COSCC is locally aggressive with up to 20% of patients showing regional or distant metastasis at the time of diagnosis. The treatment of choice most typically involves wide surgical excision. Although long-term remission is possible, treatments are associated with considerable morbidity and can negatively impact functionality and quality of life. OSCCs have substantial upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously hypothesized that small-molecule inhibitors that target RAS signaling might effectively inhibit tumor growth and progression. Here, we demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for human cancers, substantially inhibits the growth of six COSCC cell lines established from current patient tumor samples. We further show preliminary clinical evidence that the drug is able to cause ~ 40% and ~ 80% tumor regression in two out of four patients with spontaneously occurring COSCC, a partial response according to commonly used RECIST criteria. Given the limited treatment options available and the number of dogs for which standard of care is not acceptable, these preliminary findings provide new hope that more suitable treatment options may soon enter the veterinary clinic.

  PublisherOA PDFDOI

• Clinical application of the MEK inhibitor trametinib in dogs with oral squamous cell carcinoma

  Veterinary oncology. · 2025-11-24 · 1 citations

  articleOpen access

  Oral squamous cell carcinoma (OSCC) is a common and, if left untreated, deadly disease in dogs. The current standard of care involves wide-margin surgical excision of tumor tissue, which is frequently disfiguring. Surgical treatment can also be debilitating and lead to a reduced quality of life. Recent studies have demonstrated that OSCC in dogs typically shows highly elevated RAS signaling compared to healthy gingival tissue. Here, we examine the drug trametinib, which is FDA-approved for use in humans for BRAF-mutant melanomas, as an approach to treating OSCC in dogs. Domestic companion dogs (N = 20) with spontaneously occurring OSCC were recruited over a two-year period for an interventional study without concurrent controls. Dogs were prescribed 0.015 to 0.035 mg/kg trametinib daily to be given orally. Treatment was continued for 8 weeks, with examinations every 2 weeks. Health monitoring was conducted via routine bloodwork combined with at-home questionnaires. Tumor volume was assessed by caliper measurement and by computed tomography (CT) imaging. Tumor response categorization was based on R.E.C.I.S.T. criteria. Final R.E.C.I.S.T. categorization was based on CT measurement, while mid-experiment detection of progressive disease (PD) was based on caliper measurement. Dogs exited the study immediately upon determination of PD. Five dogs (25%) achieved a partial response (PR), and one dog (5%) had a complete response (CR) based on CT imaging at the end of 8 weeks of treatment, however cancer cells were detected by histological examination. Five dogs had stable disease (SD, 25%), and nine dogs (45%) were removed from the trial after demonstrating PD. For the seven dogs with BRAF p.V595E mutant tumors, one dog (14%) had PCR, four (57%) had PR, one (14%) had SD, and one (14%) had PD. Adverse events were rare, low grade, and resolved with outpatient supportive care. Trametinib blocks the growth of canine OSCC in approximately half of dogs, with objective response of 30% (CR+PR) and an additional 25% of dogs having SD. Overall, this work presents an effective, safe, and available targeted therapeutic approach for the treatment of OSCC tumors in dogs.

  PublisherDOI

• Clinical application of the MEK inhibitor trametinib in dogs with oral squamous cell carcinoma

  Research Square · 2025-06-17

  preprintOpen access
  PublisherOA PDFDOI

• Successful management of pneumonia and pyogranulomatous cranial mediastinitis due to <i>Coccidioides</i> species infection with fluconazole in a 3‐year‐old horse

  Equine Veterinary Education · 2024-06-24 · 1 citations

  articleOpen accessSenior author

  Summary A 3‐year‐old Quarter Horse gelding originating from Texas presented for fever and inappetence. An encapsulated, mixed echogenic cranial mediastinal mass visible ultrasonographically in the left and right fourth intercostal space that displaced the heart caudally was identified. Histological evaluation of needle biopsies obtained under general anaesthesia revealed a severe pyogranulomatous inflammatory process associated with intralesional round, 15–25 μm in diameter, thick double‐contoured cell wall fungal structures. Sequencing of products obtained from DNA extracted from the paraffin‐embedded biopsy sample and a panfungal PCR assay targeting the large ribosomal unit region had a 99.1% identity to either Coccidioides immitis or C. posadessii . Bronchoscopy revealed purulent exudate in the right primary bronchus. Cytological evaluation of bronchial alveolar lavage fluid (BALF) contained 96% moderately degenerative neutrophils and 4% macrophages. Fungal structures were not appreciated in the BALF. However, the mediastinitis could have resulted from inhalation and dissemination of arthroconidia through lymphatics or directly from the lung parenchyma. Quantitative immunodiffusion of serum for the presence of coccidioidal IgG antibodies yielded a titre of 1:256 suggestive of disseminated coccidioidomycosis. After oral fluconazole for 24 months, the horse's general health and athletic performance had returned to normal and the mediastinal mass was not appreciated sonographically.

  PublisherOA PDFDOI

• Impact of E. muris infection on B. burgdorferi–induced joint pathology in mice

  Frontiers in Immunology · 2024-08-20 · 2 citations

  articleOpen access

  Tick-borne infections are increasing in the United States and around the world. The most common tick-borne disease in the United States is Lyme disease caused by infection with the spirochete Borrelia burgdorferi ( Bb ), and pathogenesis varies from subclinical to severe. Bb infection is transmitted by Ixodes ticks, which can carry multiple other microbial pathogens, including Ehrlichia species. To address how the simultaneous inoculation of a distinct pathogen impacted the course of Bb -induced disease, we used C57BL/6 (B6) mice which are susceptible to Bb infection but develop only mild joint pathology. While infection of B6 mice with Bb alone resulted in minimal inflammatory responses, mice co-infected with both Bb and the obligate intracellular pathogen Ehrlichia muris ( Em ) displayed hematologic changes, inflammatory cytokine production, and emergency myelopoiesis similar to what was observed in mice infected only with Em . Moreover, infection of B6 mice with Bb alone resulted in no detectable joint inflammation, whereas mice co-infected with both Em and Bb exhibited significant inflammation of the ankle joint. Our findings support the concept that co-infection with Ehrlichia can exacerbate inflammation, resulting in more severe Bb -induced disease.

  PublisherOA PDFDOI

• Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas

  Research Square · 2024-05-02 · 2 citations

  preprintOpen access
  PublisherOA PDFDOI

• An Australian Shepherd with possible Behçet-like disease characterized by cutaneous and intestinal vasculitis leading to septic abdomen

  Journal of the American Veterinary Medical Association · 2024-10-18

  articleOpen access

  "An Australian Shepherd with possible Behçet-like disease characterized by cutaneous and intestinal vasculitis leading to septic abdomen" published on 18 Oct 2024 by American Veterinary Medical Association.

  PublisherOA PDFDOI

• Unilateral right mammary gland enlargement in a multiparous, pregnant 14-year-old American Quarter Horse mare

  Journal of the American Veterinary Medical Association · 2023-09-05

  article
  PublisherDOI

Recent grants

• Contribution of Campylobacter jejuni nuclease in Animal Models of Acute Infection

  NIH · $408k · 2010–2012

• NIH Grant R03AI059532

  NIH · $140k · 2008

Frequent coauthors

• A Najman

  Hôpital Saint-Antoine

  32 shared

• Gary R. Whittaker

  Curtin University

  31 shared

• G Marchal

  Laboratoire d’Etudes du Rayonnement et de la Matière en Astrophysique et Atmosphères

  27 shared

• Rebecca E. Ruby

  University of Kentucky

  26 shared

• Ricardo Matos

  Universidade de São Paulo

  25 shared

• Alison E. Stout

  New York University

  25 shared

• Danielle K. Tarbert

  Veterinary Medical Teaching Hospital

  25 shared

• Deanna M. W. Schaefer

  25 shared

Education

• PhD, Anatomic Pathology

  University of California Davis

  1986

• DVM, School of Veterinary Medicine

  University of Montreal

  1980