The Pilot and Feasibility Program has been an essential and strong component of this Center over the nine years since its inception. Major areas that have been studied by previous Pilot and Feasibility projects include a wide range of topics, from basic and translational studies of podocyte injury and interstitial fibrosis related to cystic disease to examination of the C. elegans excretory cell. New investigators have been brought to study areas relevant to the kidney. These include studies of the C. elegans excretory cell, by an eminent cell biologist, Dr. David Miller, and role of NFATc-1, expanding observations in the heart to the kidney, by a pediatric cardiologist, Dr. Scott Baldwin. The project of Dr. Anne Stevens, a rheumatologist at University of Washington, focused on the role of maternal microchimerism in renal fibrosis.
From the first year of the most recent funding period (2007), we had two continuing Pilot projects. The first one was led by Dr. Charles Alpers, an established renal pathology investigator from University of Washington. This project aimed to examine a new area, namely mechanisms of innate immunity of the podocyte, examining the role of Toll-like receptor 4 (TLR4) in a variety of experimental and human disease settings. Dr. Jamshid Khoshnoodi at Vanderbilt, a junior investigator, led a second project to examine key mechanisms of glomerular dysfunction in type 2 diabetes. His study aimed to examine novel inhibitors of advanced glycation and lipoxidation end products (AGE and ALE) by proteomic level analysis of the global progressive changes in the serum and glomerular proteins in response to diabetes, and the impact of inhibition of AGEs and ALEs with pyridoxamine. The goal was to identify potential biomarkers as indicators of early diabetic renal disease.
In 2008, two new pilots again were chosen. Studies of epithelial cell morphogenesis and polarity, focusing on claudin-2, by Dr. Amar Singh, then junior investigator in nephrology, have led to further R01 funding fro Dr. SIngh. The second pilot was led by Dr. Ji Ma, junior investigator in pediatric nephrology, and examined effects of key modulators of hypertension and thrombosis/fibrosis in the heart. She has since received a a grant from the AHA to examine related topics of glomerular development and injury, and consequences for kidney injury and hypertension. We then were able to fund two additional pilots from 2009-2011 from additional ARRA funds. The first of these has undertaken novel high risk approaches to screen for Wilms’ tumor-associated genes using a novel conditional transposon-based mutagenesis strategy, led by an established investigator, Dr. Mark deCaestecker in nephrology at Vanderbilt. Dr. Reena Rao received the second ARRA-funded pilot project that explored potential novel targets in acute kidney injury, resulting in subsequent R01 funding and transition to a tenure track faculty position at University of Kansas in 2011.
The most recent pilot projects starting in 2010 (ending June 30, 2012) both were made to junior investigators at Vanderbilt. Dr. Leslie Gewin’s project examines the role of TGFb in fibroblasts in relationship to an epithelial cell phenotype, and has already resulted in a VA career development award to her. Lastly, the pilot project of Dr. Fenghua Zeng examines a novel target in diabetic nephropathy, heparin binding EGF-like growth factor, and has already resulted in an abstract.
Thus, the Pilot and Feasibility projects from the last 4 years have already resulted in 2 RO1s, one AHA, and one VA Career development award. The pilot investigators have also been quite productive, with a total of 40 manuscripts published since their pilots were received and an additional 28 abstracts not yet published as full papers.
We will continue to follow our usual time cycle, thus issuing the next RFA in early January 2012, and then consider submitted proposals at our next annual retreat in spring 2012, selecting 2 pilots from received applications for funding, as part of a possible successful competing renewal application.
In summary, the above Pilot and Feasibility projects have funded a rich and diverse research group, and fostered exchange of scientific knowledge and furthered mentoring for the junior members of our Center, enhancing their career and scientific development, both through our ongoing research in progress conferences, and our annual retreat.