Genomes and Genes
Ribonuclease 7: Antimicrobial Activity in the Human Kidney and Urinary Tract
Principal Investigator: John David Spencer
Abstract: DESCRIPTION (provided by applicant): The candidate's long-term goal is to become an accomplished independent physician-scientist in academic pediatric nephrology with clinical and research expertise in the diagnosis, treatment, and prevention of urinary tract infections (UTI). This mentored K08 Career Development Award proposal outlines a plan where the candidate will train under the guidance of a team of mentors and collaborators that have a successful track record of working together. This Research Advisory Team has extensive experience and success in guiding trainees and junior faculty to successful careers as independent physician-scientists. The candidate will benefit from state-of-the-art facilities and extensive support from clinical, basic, and general core services. He will acquire new research and analytical skills from hands-on directed laboratory mentorship and a classroom- based education at The Ohio State University. He will build a repertoire of competencies in oral and written scientific communication;academic team leadership and collaboration;and grantsmanship. The long-term objectives of the proposed research project are to improve the care of pediatric patients with UTIs by identifying effective early biomarkers and novel treatment options for the diagnosis and treatment of UTIs. The proposed research project will test the hypothesis that antimicrobial peptides (AMP), a ubiquitous component of the innate immune system, are important in the regulation and prevention of UTIs. The proposed research will define the function of a novel AMP, ribonuclease 7 (RNase 7), which has recently been shown to have potent antimicrobial properties and play an important role in maintaining urinary tract sterility. The anticipated outcome of this work is advancement of our understanding of the role of RNase 7 in the prevention and treatment of UTIs and to identify the potential use of this protein in UTI diagnostics and therapeutics. Specific Aim 1 is designed to characterize the antimicrobial properties of RNase 7 in states of health and infection. Specific Aim 2 is designed to characterize RNase 7 at the structural and functional level by identifying critical amino acid residues that are responsible for its antimicrobial function. Specific Aim 3 is designed to evaluate the frequency and biological relevance of single nucleotide polymorphisms in RNASE7. Successful completion of these proposed aims and educational plan will help develop the needed expertise to systematically evaluate AMPs, like RNase 7, in the human urinary tract.
Funding Period: 2012-08-01 - 2017-05-31
more information: NIH RePORT
- Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tractJohn David Spencer
Department of Pediatrics, Division of Nephrology, Nationwide Children s Hospital, Columbus, Ohio 43205, USA
Kidney Int 83:615-25. 2013..Thus, RNase 7 expression is increased in the urinary tract with infection and has antibacterial activity against uropathogens at micromolar concentrations...
- The innate immune response during urinary tract infection and pyelonephritisJohn David Spencer
Department of Pediatrics, Division of Nephrology, Nationwide Children s Hospital, 700 Children s Drive, Columbus, OH, 43205, USA
Pediatr Nephrol 29:1139-49. 2014..In doing so, we focus on the role of antimicrobial peptides-a ubiquitous component of the innate immune response. ..
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