Research Interests

Cell proliferation and differentiation are regulated by the interaction of both positive and negative factors. The aberrant expression of these factors can direct a cell toward either a proliferation or differentiation pathway. Little is known of the mechanisms by which proliferation and differentiation-specific factors interact. To study these interactions we have employed two distinct systems: highly proliferative, relatively undifferentiated canine osteosarcoma cell lines and a highly differentiated epithelial cell in which proliferation is developmentally regulated.

Canine osteosarcoma is a highly malignant tumor with a poor clinical prognosis. Despite the large body of information on human OS, little is known about the molecular defects that are responsible for the pathogenesis of the canine disease. We have established five canine osteosarcoma cell lines from independent animals with the goal of identifying the oncogenes, tumor suppressor genes, and signaling pathways that are aberrantly regulated and the mechanisms by which these mutant proteins and pathways control cellular proliferation and differentiation.

Alveolar type 2 cells are highly differentiated epithelial cells whose primary function is the synthesis of surfactant proteins. Alterations in the growth potential and/or differentiation of these cells blocks surfactant synthesis and is associated clinically with respiratory distress syndrome. Mature type 2 cells are first detected during day 18 of fetal rat development. Fetal type 2 cells proliferate in vivo and in vitro, whereas type 2 cells from neonate or adult rats grow poorly or not at all. Using an immortalized fetal lung epithelial cell line and differential mRNA display techniques, we are screening cDNA libraries to identify and study genes that regulate type 2 cell proliferation and differentiation.