This proposal describes a 5 year training program for the development of an academic career in Laboratory Medicine. The principle investigator (PI) has completed a structured residency training in Internal Medicine at Northwestern University followed by clinical Nephrology fellowship at UT Southwestern and a NIH sponsored post doctoral fellowship in the Division of Nephrology at UT Southwestern (2005-08). Dr Peter Igarashi, MD, Professor and Chief, Division of Nephrology, UT Southwestern, will mentor the PI during the course of this award. Dr Igarashi is an expert in the field of PKD and has successfully mentored numerous fellows and graduate students in the past. Dr Eric Olson, PhD, Professor and Chair of Molecular Biology, UT Southwestern will also mentor the PI. Dr Olson is a world renowned researcher and a expert in the field of micro-RNAs. Dr Olson will provide guidance and advice during the course of this award. Dr Olson's lab group will share reagents and resources with the PI. The research will focus on elucidating the role of micro-RNAs in kidney development and polycystic kidney disease. We and others have recently shown that early neonatal mouse kidney is a cyst prone state due to high rates of proliferation and gene expression profile of a developing kidney. On the other hand, adult kidney is a cyst resistant state due to low rates of proliferation and gene expression profile of a mature kidney. In this proposal we will determine whether changes in micro-RNA expression underlies the change in gene expression and decline in proliferation observed between the neonatal kidney and mature kidney. Furthermore, we will study whether aberrant micro-RNA expression is observed in murine models of PKD. These studies will be conducted at UT Southwestern, which provides an ideal setting for development of physician-scientists due to the presence of established faculty with diverse research interests and expertise. The PI will have unrestricted access to the resources provided by UT Southwestern O'Brien Kidney center core. The PI will spend 80% of time performing research related activities and 20% of time in clinical and training responsibilites. An advisory committee will oversee the progress of this proposal.
Currently no effective treatment for PKD exists. Results of our studies may reveal that novel genetic factors called microRNAs are abnormally expressed in mice with PKD. Recently, modulation of microRNA expression has been shown to successfully decrease serum cholesterol levels. Our studies will use similar modulation of microRNAs to treat PKD in mice. These treatment strategy can be eventually applied to humans with PKD.
|Aboudehen, Karam; Noureddine, Lama; Cobo-Stark, Patricia et al. (2017) Hepatocyte Nuclear Factor-1? Regulates Urinary Concentration and Response to Hypertonicity. J Am Soc Nephrol 28:2887-2900|
|Hajarnis, Sachin S; Patel, Vishal; Aboudehen, Karam et al. (2015) Transcription Factor Hepatocyte Nuclear Factor-1? (HNF-1?) Regulates MicroRNA-200 Expression through a Long Noncoding RNA. J Biol Chem 290:24793-805|
|Williams, Scott S; Cobo-Stark, Patricia; Hajarnis, Sachin et al. (2014) Tissue-specific regulation of the mouse Pkhd1 (ARPKD) gene promoter. Am J Physiol Renal Physiol 307:F356-68|
|Patel, Vishal; Williams, Darren; Hajarnis, Sachin et al. (2013) miR-17~92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease. Proc Natl Acad Sci U S A 110:10765-70|
|Noureddine, Lama; Hajarnis, Sachin; Patel, Vishal (2013) MicroRNAs and Polycystic Kidney Disease. Drug Discov Today Dis Models 10:e137-e1743|
|Patel, Vishal; Noureddine, Lama (2012) MicroRNAs and fibrosis. Curr Opin Nephrol Hypertens 21:410-6|
|Patel, Vishal; Hajarnis, Sachin; Williams, Darren et al. (2012) MicroRNAs regulate renal tubule maturation through modulation of Pkd1. J Am Soc Nephrol 23:1941-8|
|Patel, Vishal (2011) Tagged fibrocystin sheds its secrets. J Am Soc Nephrol 22:2148-50|
|Patel, Vishal (2010) Balancing the Wnts in polycystic kidney disease. J Am Soc Nephrol 21:1412-4|