This application is for a K01 Mentored Career Development Award to Promote Faculty Diversity in Biomedical Research. Dr. Trevejo-Nunez will investigate the role of IL-22/ IL-22RA2 during pneumococcal pneumonia. In United States, pneumococcal pneumonia (lung infection caused by S. pneumoniae) accounts for significant percentage of morbidity and mortality. The most vulnerable population are children younger than 2 years old and individuals older than 65. The candidate has data that shows IL-22 signaling in the liver is important for control of pneumococcal pneumonia and that treatment with the cytokine IL-22 improves bacterial burden. The overall hypothesis is that enhancement of IL-22 signaling, through therapeutic administration of IL-22 or absence of decoy recptor IL-22RA2, favors bacterial clearance and host survival by sustaining the levels of STAT3 activation in lung epithelium and liver during in pneumococcal pneumonia. To test this hypothesis, the candidate proposes 1) Define the lung cellular sources of endogenous decoy receptor IL-22RA2 in the uninfected hosts and during pneumococcal pneumonia. 2) Test the prediction that enhanced IL-22RA1 signaling in target tissues controls bacterial burden during pneumococcal pneumonia. 3) Test the prediction that enhanced IL-22 signaling results in sustained STAT-3 activation imdependent of gp130/SOCS3 in lung epithelium and liver. Dr. Trevejo-Nunez is Postdoctoral Associate of Pediatrics/ Instructor of Medicine at the University of Pittsburgh School of Medicine. She proposes a career development plan that focuses on: one- to- one meetings with her mentor Dr. Jay Kolls every week, learning mouse model of infection using transgenic and conditional knockout mice, attending academic coursework to strengthen her foundation in immunology, statistics, experimental design and grant writing; participating in responsible conduct of research workshops, meeting with her review advisory committee every 6 months, attending conferences and publishing manuscripts as first author. Dr. Trevejo-Nunez's long term goal is to become an independent physician- scientist with particular expertise in the immunology and host response against S. pneumoniae lung infection. The candidate also plans to gather enough information and analysis of data to apply for R01 funding at the end of this award.
Pneumonia due to pneumococcus is a common cause of death worldwide. This proposal will help in understanding the role of a molecular messenger (IL-22) and its natural inhibitory molecule (IL-22RA2) to enhance the response against infection, to prevent and to treat pneumococcal pneumonia. It will also give insight of future targets for therapy.