Neurodevelopment/Cancer

Description of projects available to graduate students:
Glucocorticoid hormones are widely used as prenatal agents for mothers at risk for preterm delivery and as postnatal agents in premature infants in order to decrease medical complications of prematurity. However, animal and clinical studies suggest that exposure of fetuses to glucocorticoids during development could affect future cognitive function and brain development. Delayed neurological effects of early glucocorticoid exposure may be mediated by reduced neural progenitor cell survival, proliferation or differentiation. We are using a number of in vivo and in vitro models to examine the role of the glucocorticoid receptor protein in survival and function of developing neurons in the cerebral cortex. Both genomic and nongenomic mechanisms of glucocorticoid receptor action are being studied to uncover both short and long term effects of these hormones.


Communication between the epithelial and stromal compartments of the prostate that is mediated by growth factors and cytokines is crucial for the maintenance of prostate growth and function. However, alterations in the expression and response to these factors can occur during prostate cancer progression and alter signaling between these compartments. We are examining various signaling pathways within the tumor microenvironment that mediate cross talk between cells within the stromal compartment and prostate cancer cells. For example, we have identified a prostate stromal cell specific transcriptional coactivator, the Hic-5 protein, that functions in both androgen and vitamin D signaling pathways. Hic-5 influences androgen regulation of paracrine factors in stromal cells. In addition, it is an important mediator of vitamin D response acting to regulate vitamin D metabolism in stromal cells and the antiproliferative response of this vitamin in prostate cancer cells. We are also studying the TGF-beta signaling pathway with a particular interest in understanding the mechanism for its divergent action as both a tumor suppressor and tumor promoter. Recent studies revealed that human prostate cancer associated fibroblasts maintain a secreted activity that limits the migration of prostate cancer cells. However, TGF-beta derived from aggressive prostate cancer cells can block this migration inhibitory activity through activation of an ROS signaling pathway in the cancer-associated fibroblasts.

Techniques graduate student will learn:
Neural stem cell cultures; mammalian cell culture; gene expression analysis; cell signaling assays