The overall research program in our laboratory involves understanding the regulatory processes controlling an organism's response to environmental stress. In particular, we are interested in how organisms respond when they are exposed to toxic concentrations of transition metals. The current focus of our research is directed toward understanding how cadmium induces the expression of dozens of different genes, which encode proteins with functions ranging from repairing intracellular damage to DNA, lipids and proteins to activating signal transduction cascades. Results from this research will help elucidate (a) mechanisms of transition metal induced disease, developmental abnormalities and carcinogenesis and (b) how organisms adapt to increasingly toxic environments. A second area of research focuses on understanding the regulatory mechanism of metallothionein gene transcription. Multiple transcription factors, including those involved in metalloregulation, development and cell-specificity, must coordinately interact to activate metallothionein gene transcription. Defining these processes are essential to understanding metal-responsive gene regulation in vertebrates and the roles of transition metals in carcinogenesis. Finally, in collaboration with several members of the Integrated Toxicology Program, the Duke University Superfund Basic Research Program, and the Center for Environmental Genomics we are exploring the mechanism by which environmental toxicants affect gene expression. These studies will address the ability of toxicants to induce developmental abnormalities.
Contact Freedman at:
NIEHS, MD E1-05
P.O. Box 12233
RTP, NC 27709
919-541-7899
fax: 919-541-3641
freedma1@niehs.nih.gov