- Ph.D., Baylor College of Medicine
- Postdoc., Vanderbilt University College of Medicine
Development and Differentiation, Mechanisms of Transcription Factor Action
Our research interests are directed towards understanding the complex mechanisms which regulate the expression of specific gene sequences in development. We have focused our studies upon the factors that influence the smooth muscle component of the developing gastrointestinal (G.I.) tract. It has been shown that smooth muscle cells are predominantly derived from mesodermal precursor cells, however the factors regulating the selection of the smooth muscle myogenic pathway is not well defined.
We have shown that there is a definant lineage of smooth muscle during development and that the terminal differentiation of these cells requires an upregulation in expression of the trans-factor Serum Response Factor (SRF). This factor is known to work in conjunction with other partner proteins to engage cell specific transcriptional responses. Current studies in the lab are focused upon determining the identity of these partner proteins and showing how they work with SRF to achieve smooth muscle terminal differentiation. We have initiated these experiments looking at the mammalian homologs of the Drosophila bagpipe protein, termed Nkx3.1 and Nkx3.2. The studies utilize molecular and cellular biological techniques in combination with transgenic mouse knockout technologies to directly examine the ability of these factors to influence development.
Additionally, our recent transgenic studies have allowed an investigation of signaling pathways potentially governing smooth muscle cell differentiation. Interestingly, these studies have shown a convergence of pathways upon SRF in smooth muscle and these pathways may be influential in developing prostate and osteogenesis. We believe that our studies will reveal molecular mechanisms which underlie changes in metabolism growth control in smooth muscle which are associated with the primary physiological responses of these cells in vascular and viscual injury and disease states. In addition we will gain knowledge of mechanisms that are influential for bone and prostate development and disease, such as prostate cancer.