Fred Quimby, College of Veterinary Medicine

Autoimmunity, immunodeficiency, and immunotoxicologic disorders in dogs. We have developed monoclonal antibodies directed against a variety of cell surface antigens of canine lymphocytes. Antigens specified by these MoAb have been characterized using gel electrophoresis and Western blot analyses. These MoAb have been used to characterize and isolate canine Lymphocyte subpopulations using cytofluoremetry and cell-sorting techniques.

Recent studies have been directed at developing lymphoma/leukemia-specific monoclonal antibodies that can be used to localize immunotoxicants on malignant target tissues. We developed an immunophenotypic genotypic classification of canine Lymphomas and compared it to morphologic classification, biologic behavior, and response to chemotherapy. Both Southern blotting with radiolabeled DNA probes and immunoperoxidase procedures were employed in these studies. Monoclonal antibodies and functional assays are being used to characterize immunotoxic effects of environmentalpollutants and spontaneous immune mediated diseases in the dog. Canine models for familial Mediterranean Fever and Common Variable Immunodeficiency have been described in our laboratory.

Recent studies have concentrated on the molecular defect responsible for immunodeficiency in dogs (including pets) exposed to low doses of environmental polychlorinated biphenyls (PCBs). In addition, we discovered that low levels of PCBs cause alterations in endocrine, reproductive, gastrointestinal, lacrimal and central nervous systems of dogs.

Ken Rassnick, College of Veterinary Medicine
Cancer chemotherapy and pharmacology. Development of new strategies for cancer control in a primary translational and clinical format.

Mark Roberson, College of Veterinary Medicine

Gonadotropin releasing hormone (GnRH) is absolutely required for normal production of gonadotropins and subsequent gonadal function in mammals. Therapeutics for the positive and negative regulation of fertility has focused on manipulation of the GnRH system. My research in this area examines the intracellular signal transduction cascades induced by GnRH and the mechanisms of gene activation that results from these signaling cascades.

Our cell signaling studies emphasize regulation and combinatorial effects of the mitogen-activated protein kinase pathways and the interrelationships between MAPK pathways and mobilization of calcium on target gene activation. The gene targets of these pathways include the glycoprotein hormone a subunit (a component of chorionic gonadotropin, luteinizing- and follicle-stimulating hormones), the GnRH receptor gene, the proto-oncogenes c-fos and c-jun and a newly described MAPK phosphatase, MKP-2.

Our long-term goal is the identification of the complement of genes induced by GnRH receptor occupancy and the cellular mechanisms involved in the regulation of GnRH hormone action on pituitary-specific gene expression. Anyone of these GnRH-dependent genes represents a potential target for fertility regulation in mammals.