Kidney Development Nephron Regulation
Abnormal kidney development is the most common cause of kidney failure in infants and children. Available treatments include dialysis and transplantation, but no cure. Research in our lab is focused on understanding the basic mechanisms of kidney development, with emphasis on regulation of nephron progenitor cell renewal by energy metabolism and the transcription factor p53. Read More
Nephron abundance varies among individuals and populations, with demonstrated influence of genetics and maternal nutritional status on nephron number in humans. Impaired nephron progenitor cell renewal in embryogenesis results in fewer nephrons; low nephron number at birth is strongly associated with adult onset diseases such as hypertension and chronic kidney disease. We are using mouse models, kidney organ culture, primary cell culture, RNA-Seq, chromatin immunoprecipitation and metabolic profiling to characterize requirements for nephron stem cell renewal versus differentiation in vivo as well as at molecular and biochemical levels.
How the metabolic status of the nephron stem cell switches the cellular program from self-renewal to nephrogenesis has potentially huge implications on the influence of the maternal environment on embryonic kidney development. The knowledge gained can be utilized to adjust maternal conditions for optimal nephrogenesis during fetal development and towards regenerative therapies.
Anna Abrams, M.S. – Medical student
Francesca Edgington-Giordano - Graduate student
Harrison Lindley - Graduate student
Jiao Liu, M.S. – Laboratory technician
Yashna Singh, M.D. - Fellow
1. Li Y, Liu J, Li W, Brown A, Baddoo M, Li M, Carroll T, Oxburgh L, Feng Y and Saifudeen Z. p53 Enables Metabolic Fitness and Self-Renewal of Nephron Progenitor Cells. Development, 2015 Apr 1; 142(7):1228-41. doi: 10.1242/dev.111617. PMID: 25804735
2. El-Dahr SS, Hilliard S, Aboudehen K, Saifudeen Z. The MDM2-p53 pathway: multiple roles in kidney development. Pediatr Nephrol. 2013 Sep 28. PMID: 24077661
3. Li Y, Liu J, McLaughlin N, Bachvarov D, *Saifudeen Z and El-Dahr SS. Genome-wide Analysis of the p53 Gene Regulatory Network in the Developing Mouse Kidney. Physiol Genomics. 2013 Sep 3. PMID: 24003036
4. El-Dahr SS, Saifudeen Z. Interactions between BdkrB2 and p53 genes in the developing kidney. Biol Chem. 2013 Mar 394(3):347-51. PMID: 23152407
5. *Saifudeen Z, Liu J, Dipp S, Yao X, Li Y, McLaughlin N, Aboudehen K, El-Dahr SS. A p53-Pax2 Pathway in Kidney Development: Implications for Nephrogenesis. PLoS One. 2012; 7(9):e44869. doi: 10.1371/journal.pone.0044869. PMID: 22984579
6. Aboudehen K, Hilliard S, Saifudeen Z and El-Dahr SS. Mechanisms of p53 Activation and Physiological Relevance in the Developing Kidney. Am J Physiol (Renal) 2012 Apr 15; 302(8):F928-40.
7. *Saifudeen Z, Dipp S, Stefkova J, Yao X, Lookabaugh S and El-Dahr SS. P53 Regulates Metanephric Development. J Am Soc Nephrol. 2009 Nov; 20(11):2328-37. PMC2799183
8. El-Dahr SS, Aboudehen K, Saifudeen Z. Transcriptional Control of Terminal Nephron Differentiation. Am J Physiol (Renal) 294(6):F1273-8, 2008 PMC2606293
9. Saifudeen Z, Diavolitsis V, Dipp S, Fan, H, and El-Dahr SS. Spatiotemporal switch from Np73 to TAp73 isoforms during nephrogenesis: impact on differentiation gene expression. J Biol Chem. 280: 23094 – 23102, 2005.
10. Saifudeen Z, Dipp S and El-Dahr SS. A Role for p53 in Terminal Epithelial Cell Differentiation. J. Clin. Invest. 109: 1021-1030, 2002.
Pubmed listing of research publications: