Ribonuclease 7: Antimicrobial Activity in the Human Kidney and Urinary Tract

Summary

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

Top Publications

  1. pmc Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract
    John David Spencer
    Department of Pediatrics, Division of Nephrology, Nationwide Children s Hospital, Columbus, Ohio 43205, USA
    Kidney Int 83:615-25. 2013
  2. pmc The innate immune response during urinary tract infection and pyelonephritis
    John 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

Detail Information

Publications2

  1. pmc Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract
    John 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...
  2. pmc The innate immune response during urinary tract infection and pyelonephritis
    John 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. ..

Research Grants30

  1. IRON LIPOCALIN NGAL IN KIDNEY DISEASE
    Jonathan M Barasch; Fiscal Year: 2013
    ..We propose that these experiments explain why uNGAL is massively expressed in damaged kidney and they test the notion that NGAL is a conserved defense against uro-gential infections regardless of the inducing stimulus. ..
  2. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  3. Southeast Regional Centers of Excellence for Biodefense &Emerging Infectious Di
    Philip Frederick Sparling; Fiscal Year: 2013
    ..SERCEB brings new investigators to the biodefense effort through a combination of educational programs, support of innovative new projects, and the synergistic interactions among its world-class investigators. ..
  4. New England Regional Center of Excellence in Biodefense and Emerging Infectious D
    Dennis L Kasper; Fiscal Year: 2013
    ..NERCE will also continue its Developmental Projects program and Career Development in Biodefense program in an effort to initiate new research efforts and to attract new investigators to this field. ..
  5. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
    ..As a Center based in a School of Public Health and a State Department of Health, the NBC has a firm commitment to and practical understanding of Emergency Preparedness. ..
  6. Center for Gene Therapy of Cystic Firbosis
    John F Engelhardt; Fiscal Year: 2013
    ..These efforts have led to numerous basic and applied research findings that have enhanced the utility of gene therapies to both study and treat genetic diseases. ..
  7. Boosting Innate Immunity Through HIF to Treat Antibiotic-Resistant Infections
    ROBERT ALAN SHALWITZ; Fiscal Year: 2013
    ..Ultimately, HIF-1 immune boosting therapy could find wide application in the treatment of difficult infections complicated by antibiotic resistance or weakened host defense. ..
  8. Molecular Analyses and Interventions for Biodefense and Emerging Pathogens
    Olaf Schneewind; Fiscal Year: 2013
    ..Research and training at the GLRCE is governed by a mechanism involving ongoing review of scientific excellence and translational goals, inter-institutional advisory boards and external scientific advisory bodies. ..
  9. MOLECULAR GENETICS OF COAGULATION DISORDERS
    David Ginsburg; Fiscal Year: 2013
    ..This Project will identify key genes in this system that should provide valuable new diagnostic tools as well as suggest novel approaches to treatment. ..
  10. Fusobacterial associated beta defensin inducer
    Aaron Weinberg; Fiscal Year: 2013
    ....