Research

Veterinary Pathology

The Section of Veterinary Pathology includes both the Anatomic and Clinical Pathology laboratories. These laboratories provide disease surveillance, diagnostic services, production of unique biologics, GLP drug safety testing and research support for clinicians and investigators using animals in this department and the institution. General laboratory services include hematologic, serum chemical, serologic, parasitologic and microbiologic analyses as well as necropsy (autopsy) and histopathologic evaluations. Similar services and support may be provided to other state institutions and extramural organizations upon request.

The major goal of the 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 (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 data indicating that folic acid can prevent the development of both intrinsic and acquired resistance to cisplatin in lung and ovarian cancer cell lines.

Immunotherapeutic Reagents Against Ovarian Cancer

Dr. Feng Wang-Joahnning and Dr. Nehete are studying human endogenous retroviruses (HERVs) in human cancers. Her 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.

Dr. Satterfield is working with Dr. Molly Brewer (Department of Gynecologic Oncology) on potential mechanisms of chemoprevention of ovarian cancer in women at high risk using a nonhuman primate model. In this two-year program, we are evaluating the effects of two chemicals with ovarian activity -- 4-hydroxyphenylretinamine and a commercially available oral contraceptive -- on the epithelium of the ovary in this model. This program includes the testing of a new device that is capable of measuring changes in the fluorescence and reflectance of light from tissue suspected to be malignant. The technology, developed by bioengineers at The University of Texas at Austin, is also being used in this project to evaluate the chemoprotective potential of the drugs in preventing ovarian cancer in humans.

Influence of Psychosocial Variables on Immune Responses and Health

Psychosocial variables influence several aspects of immune and nervous systems, but the molecular mechanisms are not very well understood. In collaboration Dr. Steven Schapiro and Dr. Nehete are studying the relationship between behavioral factors and the immune and nervous system using rhesus macaques and chimpanzees as models. To date, in the rhesus macaques, we have demonstrated associations between certain measures of cell-mediated immunity and dominance status as well as environmental enrichment. At present, we are studying stress during blood sampling (by comparing volunteering versus anesthesia-dependent) as a co-factor on the immune system and neurotransmitters 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

Drs. Nehete and Satterfield are looking at hepatitis C virus (HCV) infection and vaccination in chimpanzees in collaboration. Specifically, they are analyzing blood samples obtained from chimpanzees for cell-mediated immunity (CMI) responses (which include antigen-specific proliferation and ELISPOT analysis) to HCV vaccination to assess protective efficacy against HCV infection.