The Veterinary Pathology Section includes both the Clinical and Anatomic Pathology Laboratories. These laboratories provide disease surveillance, diagnostic services, and production of unique biologics, tissue banking, GLP drug safety testing, and research support for clinicians and investigators using animals in this department and the institution. General laboratory services include hematological, serum chemical, serological, parasitological and microbiological analyses as well as necropsy (autopsy) and histopathological evaluations. Similar services and support may be provided to other state institutions and extramural organizations upon request.
Immunotherapeutic Reagents Against Ovarian Cancer
Dr. Feng Wang-Johanning and Dr. Gary Johanning are studying human endogenous retroviruses (HERVs) in human cancers. Their hypothesis is that multiple HERV env proteins expressed in ovarian cancer may serve as novel tumor markers that can be targeted for development of an immunotherapeutic vaccine against ovarian cancer. This research has led to the discovery of new breast cancer therapeutic monoclonal antibodies and the development of early breast cancer tests.
Folic Acid and Resistance to Cisplatin
One major area of research in our laboratory is to determine the role of the vitamin folic acid (folate) in carcinogenesis and cancer prevention. An important aspect of this research is evaluating the influence of folic acid on the development of resistance to cisplatin and other chemotherapeutic agents. Cancer cells can become resistant to the cytotoxic action of chemotherapeutic agents either at the outset of therapy (intrinsic resistance) or after the agents are administered for a period of time (acquired resistance). Resistance to cisplatin and other agents is an important problem in cancer therapy, and the mechanism by which resistance develops is not clear. We have in vitro and in vivo data indicating that folic acid can prevent the development of both intrinsic and acquired resistance to cisplatin in lung and ovarian cancer cell lines.
Influence of Psychosocial Variables on Immune Responses and Health
Psychosocial variables influence several aspects of the immune and nervous systems, but the molecular mechanisms are not very well understood. In a collaborative project between behavioral management and immunology, we are studying the relationship between behavioral factors and the immune and nervous system using rhesus monkeys and chimpanzees as models. To date, in the rhesus monkeys, we have demonstrated that certain measures of cell-mediated immunity are associated with both dominance status and environmental enrichment. At present, we are studying stress during blood sampling (by comparing voluntary versus anesthesia-dependent sampling) as a cofactor on the responses of the immune system and neurotransmitter levels in chimpanzees. The psychosocial, immunological and neurological parameters will have important implications for the management, treatment and selection of nonhuman primates as models for vaccine development and drug testing of immunotherapeutics. The enhanced understanding of the immune system of nonhuman primates will improve the implementation and interpretation of these studies for human diseases.
Our studies of enrichment, positive reinforcement training and socialization strategies in chimpanzees and rhesus monkeys have identified a number of beneficial behavioral management strategies that are currently being implemented in our colonies and disseminated to other groups of primate users. Because federal regulations mandate the promotion of psychological well-being in laboratory primates, these types of empirical investigations are of critical importance. Positive reinforcement training is currently being emphasized and studied as an independent variable and as a mechanism for providing the animals with the opportunity to voluntarily participate in necessary husbandry, veterinary and research procedures.
Cellular Immune Response Against Hepatitis C Virus
Investigations are under way to study hepatitis C virus (HCV) infection and vaccination in chimpanzees. Specifically, we are analyzing blood samples obtained from chimpanzees for cell-mediated immunity responses (which include antigen-specific proliferation and ELISPOT analysis) to HCV vaccination to assess the vaccine’s protective efficacy against HCV infection.
Synthetic Peptide-Based Vaccines and Therapeutics Against HIV
A research program in viral oncology and immunology focuses on the development of synthetic peptide-based vaccines and therapeutics against HIV. The synthetic peptide approach offers the advantage of being defined, safe and economical.
Synthetic Peptide Therapeutic Targeting Host Human Cells to Prevent Entry of HIV
The peptide therapeutic targets a critical interaction between the HIV envelope and host cell surface glycosphingolipids (GSL) that we discovered in collaboration with scientists from France to be essential for entry and infection by the vast majority of HIV strains around the world. Thus, compared to the current standard therapy targeting the virus after it gains entry into cells, this novel strategy attempts to target HIV outside the host cell to block viral entry. From the basic science standpoint, our discovery of GSL as an additional, but essential, cofactor for viral entry is extremely important in unraveling the complexity associated with HIV infection and therapeutic development. The in vivo safety and efficacy of this peptide therapeutic have been demonstrated in a primate model of HIV infection. Since the target for the drug is the GSL on host cells and not the virus, no escape viral mutants developed in the vivo study or in several in vitro experiments.
Synthetic Peptide Therapeutic Targeting HIV to Prevent Infection
Two peptides, N22S and S4S, corresponding to the high-affinity gp120-binding region of CD4 were identified (20 and 4 amino acids, respectively). These peptides interact with the gp120 on diverse HIV-1 strains (both laboratory and primary isolates) to induce gp120 shedding and virus inactivation resulting in significant inhibition of infection.
Synthetic Peptide-Cocktail Vaccine Against HIV-AIDS
The vaccine is a cocktail of six peptides we discovered that correspond with highly conserved sequences in the envelope proteins of HIV strains worldwide. A unique property of the peptides is that they serve as epitopes for HLA Class I C-restricted cytotoxic T lymphocytes (CTL) in long-term non-progressors. We have successfully demonstrated the safety and efficacy of the vaccine in the SHIV-rhesus monkey model by using autologous dendritic cells (DC) to deliver the peptide cocktail for protection against chronic infection and AIDS. This vaccine-mediated protection in monkeys also translated into lack of transmission to partners in a social setting and resistance to re-challenge. We are also developing new strategies to target the peptide-cocktail vaccine to DC in vivo using reagents that would mobilize DC. (This research is supported by a National Institutes of Health [NIH] grant.) A second approach, developed in collaboration with scientists at The University of Texas Medical Branch at Galveston, is based on mucosal vaccination using novel mutant bacterial toxins as adjuvants for intranasal administration of the peptide cocktail and induction of strong systemic and mucosal cellular immune responses. Further, in collaboration with scientists from Mayo Clinic in Rochester, MN, we are also developing a DNA-vaccine strategy to express the peptide cocktail as a mixture of minigene-expressing plasmids with DC-targeting sequences.