Danny Manor, Nutritional Sciences

Transformed cells can be distinguished from normal cells by several properties; the cells become independent of anchorage, they lose their ability to undergo contact inhibition, and they become independent of blood-born growth factors for proliferation. Manor and colleagues showed for the first time that transformation by a single oncogene can be dissected on the molecular level into different signaling pathways, each of which mediates distinct facets of the overall transformation process. This notion has a significant impact on our understanding of the molecular basis of transformation, as well as on our ability to attenuate different aspects of the total transformation phenotype.

Using the Dbl oncogene as a model-system, the Manor laboratory is involved in identifying the protein molecules that participate in its distinct signal transduction pathways (via its GTP-binding protein targets Cdc42, Rac and Rho) and in assessing their contribution to the overall malignant phenotype. As these signaling participants are identified and characterized, large scale expression and protein purification will be performed in order to being three dimensional structural analyses. A second area of emphasis has to do with the role of de-regulated protein synthesis in malignant transformation. While most oncogenes are known to exert their transforming effects via the modulation of gene transcription and cytoskeletal architecture, it is becoming increasingly clear that the protein translation machinery is also adjusted to match the changing needs of the transformed cell.

Sean McDonough, College of Veterinary Medicine

I have a particular interest in the immunophenotyping canine leukemias and lymphomas.Immunophenotypic analysis is a powerful diagnostic aid that can define the lineages of these neoplastic disorders with greater precision than is possible based just on morphologic criteria. This information is also providing new insights into the biology of this complex group of diseases.

Other research interests lie in exploring the interface between adaptive and innate immunity and the role the microenvironment plays in regulating these interactions. As part of my graduate studies, I found a large population of gamma/delta T-cells resides in the red pulp of the canine spleen. Although the functions of gamma/delta T-cells are not well defined, I believe they interact with red pulp macrophages in defense against blood-borne infectious agents. Exploring the cellular and molecular basis of these potential interactions may provide new insights into the function of this important immune compartment during bacteremia and in control of hemoparasites.