Robert Oswald,College of Veterinary Medicine

The Oswald laboratory uses a combination of NMR and electrophysiology to examine the structure and function of various types of signaling proteins and ion channels. One important area of focus is the Ras-related small GTP-binding protein, Cdc42. Using the Inova 600 in the Biomolecular NMR Center, the Oswald group, in collaboration with the Cerione laboratory, solved the structure of Cdc42 in the GDP-bound form and mapped the changes in the GDP-bound vs. the GTP analog GMPPCP-bound form. This line of study has been extended to examine the interactions between Cdc42 and one of its primary target/effector proteins, the p21-activated kinase (PAK). The binding domain of PAK on Cdc42 has been identified by producing successively smaller constructs surrounding the CRIB (Cdc42/Rac-interactive-binding) sequence.

Rodney Page, College of Veterinary Medicine

The primary focus of Dr. Page's has been the characterization of large animal models of cancer. Although we use in vitro systems as well as conventional systems, characterization of spontaneous animal tumors in companion animals is the primary model of interest. We have characterized the immunologic, molecular and clinical aspects of several common tumor-types in companion animals for investigation of novel treatment strategies as a prelude to human clinical trials and in order to improve management of cancer in these species.

Recently we have characterized the immunobiology of canine non-Hodgkins lymphoma and determined the in vitro and clinical impact of the multidrug resistance gene homolog in canine cancer. The scientific value of a clinically relevant large animal model is the ease in extrapolation of results to human cancer. Promising new treatments identified in conventional animal models can be expeditiously refined for human clinical studies in such "intermediate" models. We have investigated numerous new treatment strategies and investigational compounds in clinical trials using tumor-bearing companion animals which have subsequently impacted human treatment decisions.

Examples of such studies include clinical investigation of thermochemotherapy, thermoradiotherapy, optimal dosing schemes for radiation and chemotherapy and modulation of multi-drug resistance. We have also evaluated new agents such as anti-emetics and platelet growth factor analogs in relevant canine models of chemotherapy-induced toxicity. Use of these intermediate models of cancer will become increasingly valuable to multidisciplinary teams of basic and clinical scientists as similarities in the genetic, environmental and biological manifestations of cancer to humans are further characterized.