Hormones are the major extracellular transducers of biological signals. Once hormones have relayed their signals by interacting with their target cells, the signal must be interpreted by those target cells. Understanding how the target cells "interpret" hormonal signals is the primary focus of our laboratory.Most of our research centers on regulation of steroid hormone-transduced signals. One area of study is the calcium-dependent regulation of glucocorticoid and androgen receptor-mediated transcription. We have found that knockdown of a calcium pump in the plasma membrane (PMCA1) with antisense RNA leads to a significantly elevated hormone-dependent transcriptional activity mediated by these receptors. This problem is being attacked from two ends. First, we are examining transcription factors to determine any changes in posttranslational modifications or amounts of these proteins. Second, we are evaluating changes in the known calcium signaling pathways. A second major area of interest concerns glucocorticoid and steroid sex hormone regulation of nitric oxide (NO) production. We have found that several different steroid hormones down regulate production of NO in cells stimulated with interleukin 1-beta, but do not inhibit transcription of the gene for inducible nitric oxide synthase (iNOS). Other areas of interest in our laboratory are: development of androgen-independence in prostate cancer; stress responses in PMCA1(-) cell lines; and the involvement of NO in dry eye syndrome. I participate in graduate training as a member of the faculty in the Interdisciplinary Program in Neuroscience..
Dr PAUL BRANDT
