Giraldina Trevejo-Nunez, MD, has been awarded funding in the amount of $432,980 for a two-year grant by the National Institutes of Health/National Institute of Mental Health (NIH/NIAID) entitled, “Negative regulation of inflammation during Klebsiella pneumoniae infection.” This proposal was submitted in response to the competitive funding opportunity entitled “NIH Exploratory/Developmental Research Grant Program (Parent R21)” under funding opportunity number PA-20-195.
Klebsiella pneumoniae is the third leading cause of healthcare-associated pneumonia in the United States. Infections with Klebsiella pneumoniae (KP) activate the IL-17 signaling pathway, which is crucial to constrain KP dissemination and facilitate pathogen eradication. During this process, IL-17 is negatively regulated by RNA binding proteins (RBP) in an effort to decrease collateral tissue damage in the host. One of these RBPs is Regnase-1 (Reg1) which degrades IL-17- induced transcripts. In this proposal, we will investigate the role of Reg1 in the airway epithelium during KP pneumonia. We hypothesize that Reg1 deficiency enhances the effect of pro-inflammatory transcripts in the airway epithelium which favors immunity against KP. For that purpose, we will characterize a Reg1 conditional knockout in the airway epithelium upon KP pneumonia as well as investigate Reg1 regulation at the epigenetic and post-transcriptional level.
Dr. Trevejo-Nunez’s study proposes to investigate the mechanisms by which Regnase-1 (Reg1) deficiency enhances immunity to Klebsiella pneumoniae in the lung epithelium as well as how IL-17 induces changes at the chromatin level to promote accessibility at the Reg1 locus. This new inquiry regarding host immune response in the lung epithelium upon deficiency of Reg1 against KP, a pathogen of extreme public health significance, will complement ongoing research and lead to expanded collaborative efforts.