Samir El-Dahr, MD
Chair & Professor of Pediatrics
M.D.: University of Virginia
(Molecular biology of hypertension; renin-angiotensin, kallikrein-kinins, and growth factors)
The overall theme of our research program is the cellular and molecular regulation of kidney development. Ongoing projects in the lab are:
Gene-environment interactions in renal development. A mouse model of human renal dysplasia was developed in our lab. Induction of abnormal nephron differentiation requires the cooperation of a genetic defect (bradykinin B2 receptor gene disruption) and an embryonic stressor (gestational high salt intake). Differential gene expression analysis in these mice has revealed a novel multifactorial paradigm of aberrant renal epithelial cell differentiation involving tumor suppressors, transcription factors, cell cycle proteins, and cell-cell adhesion molecules. Accordingly, the goal for the next 5 years will be to explore the individual pathways leading to aberrant renal cell differentiation.
Transcription factor p53 in terminal epithelial differentiation. The goal of this project is to elucidate the mechanisms whereby differentiating renal epithelial cells acquire functional characteristics during nephrogenesis. Ongoing studies utilizing genetically engineered mice either lacking p53 or overexpressing mutant p53 will reveal how this transcription factor regulates terminal renal cell differentiation. We have found that several renal function genes are targets for p53-mediated transcriptional activation. Moreover, some strains of p53-deficient mice exhibit abnormal renal development. In this project, the mechanisms whereby p53 couples renal cell growth with functional differentiation will be explored. The findings should provide a novel paradigm linking development and cancer.
Transcriptional regulation of the bradykinin B2 receptor gene. The goal of this project is to delineate the regulatory elements in the 5'-flanking region of the B2 receptor that mediate the tissue and cell-type-specific expression of B2 receptors in the collecting duct of the nephron and the developmental regulation of this receptor. The function of the regulatory elements will be investigated in both cell culture systems and transgenic mice.
A PubMed listing of research publications for Samir El-Dahr, M.D.