Biographical Narrative:
Dr. El-Dahr's research efforts are centered on the molecular mechanisms of renal cell differentiation. In particular, he is interested in defining the transcription factors involved in terminal renal epithelial cell differentiation. Recently, he identified the p53 transcription factor as an important regulator upstream of several renal function genes. Mutations in the p53-binding site of the human bradykinin B2 receptor promoter are associated with hypertension and end-stage-renal disease. Thus, p53 may link renal cell differentiation and functional maturation. These findings also suggest a possible novel link between cancer susceptibility and the development of renal disease and hypertension. Another aspect of his work is to define the cellular and molecular pathways leading to renal dysplasia in a mouse model of renal dysgenesis in mice lacking a GPCR, the bradykinin B2 receptor. Of particular interest is the aberrant activity of EGF-R function in this model of renal dysgenesis, thus mimicking human cystic renal dysplasia. Dr. El-Dahr has generated a mouse model of an important human renal disease that accounts for about 30% of all childhood chronic renal failure.

Selected Publications:

• El-Dahr SS, Dipp S, Meleg-Smith S, Pinna-Parpaglia P Madeddu P. Fetal ontogeny and role of metanephric bradykinin B2 receptors. Pediatr Nephrol 14:288-296 (2000)
• Saifudeen Z, Du H, Dipp S, El-Dahr SS. The bradykinin type 2 receptor is a target for p53-mediated transcriptional activation. J Biol Chem 275: 15557-155562 (2000)
• El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosypiv IV, Meleg-Smith S. Bradykinin B2 null mice are prone to renal dysplasia: gene-environment interactions in kidney development. Physiol Genomics 3: 121-131 (2000)
• Prieto M, Dipp S, Meleg-Smith S, El-Dahr SS. Ureteric bud derivatives express angiotensinogen and AT1 receptors. Physiol Genomics 6: 29-37 (2001)
• Yosipiv IV, Dipp S, El-Dahr SS. Targeted disruption of the bradykinin B2 receptor gene in mice alters the ontogeny of the renin-angiotensin system. Am J Physiol (Renal Physiol) 281: F795-F801 (2001)
• Saifudeen Z., Marks J, Du H, El-Dahr SS. Spatial repression of PCNA by p53 during kidney development. Am J Physiol (Renal Physiol) 283: F727-F733 (2002)
• Saifudeen Z, Dipp, S. El-Dahr SS. A role for p53 in terminal epithelial cell differentiation. J Clin Invest 109: 1021-1030 (2002)
• Marks J, Saifudeen Z, Dipp S, El-Dahr SS. Two functionally divergent p53-responsive elements in the rat bradykinin B2 receptor promoter. J Biol Chem 278: 34158-34166 (2003)