The goals of my research endeavors focuses on how tissue specific transcription factors regulate gene expression patterns in the developing organ and how these same transcription factors regulate homeostasis in the adult organism. We have recently identified epigenetic mechanisms of transcriptional activation associated with the protein PTIP and transcriptional repression associated with the corepressor protein Groucho4. Our long-term goals are to understand how Pax2 and Groucho4 may epigentically control the development of disease states in the adult kidney. To that end, we have gained considerable experience in protein purification methods and have been able to identify several distinct protein complexes that are either activators or repressors of gene transcription. We are utilizing cell lines as model systems to identify genes regulated by Pax2 (IMCD cells) and genes repressd by Grg4 (human podocytes). We have used RNA microarray and ChIP seq methods to identify regulated genes and will now study these genes in animal systems.
Link to PubMed Citations
Venkatareddy M1, Wang S, Yang Y, Patel S, Wickman L, Nishizono R, Chowdhury M, Hodgin J, Wiggins PA, Wiggins RC. Estimating Podocyte Number and Density Using a Single Histologic Section. J Am Soc Nephrol, 2013 Dec 19. [Epub ahead of print] PMID 24357669
Patel SR, Ranghini E, Dressler GR. Mechanisms of gene activation and repression by Pax proteins in the developing kidney. Pediatr Nephrol. 2014 Apr;29(4):589-95 [Epub ahead of print]. PMID 23996452
Patel SR, Dressler GR. The genetics and epigenetics of kidney development. Semin Nephrol. 2013 Jul;33(4):314-26. PMC3767926
Patel SR, Bhumbra S, Paknikar RS, Dressler GR. Epigentic mechanisms of Groucho/Grg/TLE mediated transcriptional repression. Molecular Cell. 27;45(2):185-95, 2012.
Stein AB, Jones TA, Herron TJ, Patel SR, Day SM, Noujaim SF, Milstein ML, Klos M, Furspan PB, Jalife J, Dressler GR. Loss of H3K4 methylation destabilizes gene expression patterns and physiological functions in adult murine cardiomyocytes. J Clin Invest. 121(7):2641–2650, 2011.
Kim D, Patel SR, Xiao H, Dressler GR. The role of PTIP in maintaining embryonic stem cell pluripotency. Stem Cells. 2009 Jul;27(7):1516-23.
Fang M, Ren H, Liu J, Cadigan KM, Patel SR, Dressler GR. Drosophila ptip is essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways. Development. 2009 Jun;136(11):1929-38.
Patel SR, Kim D, Levitan I, Dressler GR. The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. Dev Cell. 2007 Oct;13(4):580-92.
Clarke JC, Patel SR, Raymond RM Jr, Andrew S, Robinson BG, Dressler GR, Brophy PD. Regulation of c-Ret in the developing kidney is responsive to Pax2 gene dosage. Hum Mol Genet. 2006 Dec 1;15(23):3420-8. Epub 2006 Oct 17.
Lin J, Patel SR, Wang M, Dressler GR. The cysteine-rich domain protein KCP is a suppressor of transforming growth factor beta/activin signaling in renal epithelia. Mol Cell Biol. 2006 Jun;26(12):4577-85.
Patel SR, Dressler GR. BMP7 signaling in renal development and disease. Trends Mol Med. 2005 Nov;11(11):512-8. Epub 2005 Oct 10. Review.
Lin J, Patel SR, Cheng X, Cho EA, Levitan I, Ullenbruch M, Phan SH, Park JM, Dressler GR. Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates renal fibrotic disease. Nat Med. 2005 Apr;11(4):387-93. Epub 2005 Mar 27.
Patel SR, Dressler GR. Expression of Pax2 in the intermediate mesoderm is regulated by YY1. Dev Biol. 2004 Mar 15;267(2):505-16.
Hsu CH, Patel SR, Young EW. New phosphate binding agents: Ferric compounds. J Am Soc Nephrology 10 (6):1274-80, 1999.