John A. Cidlowski
John A. Cidlowski received his Ph.D. from the Medical College of Georgia in Augusta in 1975. In 1978, Cidlowski joined the faculty in the Department of Biochemistry at the University of Vermont in Burlington before becoming a professor of physiology at the University of North Carolina at Chapel Hill in 1982. Cidlowski came to NIEHS in January 1995, where he currently heads the Molecular Endocrinology Group in the Laboratory of Integrative Biology.
Our laboratory's primary interest is understanding how steroid hormones that are induced by stress -- such as glucocorticoids -- regulate the growth, differentiation, and death of both immune and nonlymphoid cells.
Currently, we are pursuing three research projects. The first centers on the regulation of apoptosis in normal and neoplastic lymphocytes by steroid hormones and other environmental agents. We are trying to define the effectors of apoptotic pathways, purify the effector proteins, and clone the genes that encode these molecules. Our laboratory has identified one nuclease, called NUC-18, that is strongly implicated as an effector of apoptosis. We hope to complete work on other enzymes soon. We are also interested in the evolution of apoptosis and are currently evaluating this process in yeast, using pulsed-field electrophoresis and yeast strains deficient in NUC-18.
A second focus of our work is elucidating the molecular mechanisms that control the expression and turnover of glucocorticoid receptors during cellular signaling. We have discovered a unique response element within the coding region of the glucocorticoid-receptor gene that is sufficient to account for homologous down-regulation of glucocorticoid receptor by its own ligand. My colleagues and I have also recently characterized the expression and function of a nonligand-binding form of glucocorticoid receptor that has the properties of a dominant, negative repressor.
Finally, we are interested in understanding how environmental molecules, such as nutrients and vitamins, regulate gene expression. Studies in our laboratory have shown that pyridoxal phosphate, the active form of vitamin B6, profoundly decreases the ability of steroid receptors to transduce signals. The molecular mechanisms responsible for this phenomenon are under investigation.