David G Besselsen

David G Besselsen

Veterinary Specialist
Adjunct Associate Professor, Animal and Comparative Biomedical Sciences
Associate Research Scientist, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Contact
(520) 626-6702

Research Interest

David Besselsen, DVM, PhD, is the Director of University Animal Care (UAC), the Attending Veterinarian. He is a board-certified veterinary specialist (Diplomate) in the American College of Laboratory Animal Medicine and the American College of Veterinary Pathology, and served as Interim Dean for the College of Veterinary Medicine from 2017-2019. In addition to his administrative and service responsibilities, Dr. Besselsen is actively engaged in research through the provision of comparative pathology support for rodent models and oversight of the gnotobiotic mouse service. He has directed UAC Pathology Services since his arrival in 1995 and has over 80 peer-reviewed publications. UAC Pathology Services provides diagnostic and comparative pathology support for the research animals and research animal facilities at the University of Arizona. Capabilities include hematology, blood chemistry, necropsy, histologic preparation and interpretation, and others.

Publications

Besselsen, D. G., Romero-Aleshire, M. J., Munger, S. J., Marcus, E. C., Henderson, K. S., & Wagner, A. M. (2008). Embryo transfer rederivation of C.B-17/Icr-Prkdc(scid) mice experimentally infected with mouse parvovirus 1. Comparative medicine, 58(4), 353-9.

We determined whether embryos derived from C.B-17/Icr-Prkdc(scid) (SCID) mice infected with mouse parvovirus (MPV) 1b and mated to MPV-naive B6C3F1 mice would transmit virus to naive recipient female mice and rederived progeny. Viral DNA was detected by quantitative PCR (qPCR) in lymphoid tissues, gonad, sperm, and feces of all MPV1b-inoculated SCID mice. Viral DNA was detected in 1 of 16 aliquots of embryos from infected male SCID mice and in 12 of 18 aliquots of embryos from infected female SCID mice. All recipient female mice implanted with embryos from infected SCID male mice and their progeny were negative by serology and qPCR. In contrast, 3 of 5 recipient female mice implanted with embryos from infected SCID female mice and 14 of 15 progeny mice from these recipients were seropositive by multiplex fluorescent immunoassay (MFI) for MPV capsid antigen (rVP2). All of these mice were negative by MFI for parvovirus nonstructural protein antigen (rNS1) and by qPCR, with the exception of 1 recipient female mouse that displayed weak rNS1 seroreactivity and low levels of MPV DNA in lymphoid tissues. Seroreactivity to rVP2 declined over time in all progeny mice from infected SCID female mice until all were seronegative by 20 wk of age, consistent with maternal antibody transfer. Given that the high levels of MPV contamination detected in our experimentally infected SCID mice are unlikely in naturally infected immunocompetent mice, these data indicate that embryo transfer rederivation is effective for the eradication of MPV from infected colonies.

Akporiaye, E. T., Bradley-Dunlop, D., Gendler, S. J., Mukherjee, P., Madsen, C. S., Hahn, T., Besselsen, D. G., Dial, S. M., Cui, H., & Trevor, K. (2007). Characterization of the MUC1.Tg/MIN transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas. Vaccine, 25(39-40), 6965-74.

A bigenic MUC1.Tg/MIN mouse model was developed by crossing Apc/(MIN/+) (MIN) mice with human MUC1 transgenic mice to evaluate MUC1 antigen-specific immunotherapy of intestinal adenomas. The MUC1.Tg/MIN mice developed adenomas at a rate comparable to that of MIN mice and had similar levels of serum MUC1 antigen. A MUC1-based vaccine consisting of MHC class I-restricted MUC1 peptides, a MHC class II-restricted pan-helper peptide, unmethylated CpG oligodeoxynucleotide and GM-CSF caused flattening of adenomas and significantly reduced the number of large adenomas. Immunization was successful in generating a MUC1-directed immune response evidenced by increased MUC1 peptide-specific anti-tumor cytotoxicity and IFN-gamma secretion by lymphocytes.

Rausch, M. P., Hahn, T., Ramanathapuram, L., Bradley-Dunlop, D., Mahadevan, D., Mercado-Pimentel, M. E., Runyan, R. B., Besselsen, D. G., Zhang, X., Cheung, H., Lee, W., Ling, L. E., & Akporiaye, E. T. (2009). An orally active small molecule TGF-beta receptor I antagonist inhibits the growth of metastatic murine breast cancer. Anticancer research, 29(6), 2099-109.

Transforming growth factor beta (TGF-beta) plays a complex role in breast carcinogenesis. Initially functioning as a tumor suppressor, this cytokine later contributes to the progression of malignant cells by enhancing their invasive and metastatic potential as well as suppressing antitumor immunity. The purpose of this study was to investigate the efficacy of SM16, a novel small molecule ALK5 kinase inhibitor, to treat a highly metastatic, TGF-beta-producing murine mammary carcinoma (4T1).

Bartlett, M. J., Flores, A. J., Dollish, H. K., Farrell, D. C., Parent, K. L., Besselsen, D. G., Heien, M. L., Doyle, K., Cowen, S. L., Steece-Collier, K., Sherman, S. J., & Falk, T. (2017). Neuroplastic mechanism of sub-anesthetic ketamine treatment to reduce development of L-DOPA-induced dyskinesia. Science Translational Medicine.
BIO5 Collaborators
David G Besselsen, Kristian Doyle
Ignatenko, N. A., Besselsen, D. G., Stringer, D. E., Blohm-Mangone, K. A., Cui, H., & Gerner, E. W. (2008). Combination chemoprevention of intestinal carcinogenesis in a murine model of familial adenomatous polyposis. Nutrition and cancer, 60 Suppl 1, 30-5.

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited syndrome in humans. The Apc(Min/+) mouse, which expresses a mutant homolog of the adenomatous polyposis coli gene, is a model of FAP in humans. Treatment with the nonsteroidal anti-inflammatory drugs (NSAIDS) sulindac or celecoxib can suppress polyp development in FAP patients, but responses are generally transient and incomplete. Combination chemoprevention with the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) and either celecoxib or sulindac was evaluated in the Apc(Min/+) mouse. Combinations of DFMO and either NSAID reduced intestinal tumor number by more than 80% (P 0.0001) compared to untreated controls. In addition to the dramatic reduction in tumor number, the combination of DFMO and sulindac reduced the development of high-grade intestinal adenomas compared to sulindac alone (P = 0.003). The fraction of high-grade intestinal adenomas remaining after treatment was similar for the combination of DFMO and celecoxib and celecoxib alone. Only combinations of DFMO plus sulindac reduced total intestinal polyamine contents compared to untreated mice. These data support the rationale for treatment of FAP patients postcolectomy with DFMO combined with either celecoxib or sulindac but indicate that sulindac may be more effective than celecoxib in reducing intestinal polyamine contents and the incidence of high-grade intestinal adenomas when combined with DFMO.