The goal of this K24 is to provide salary support for Dr. Singh to allow him to spend 40% of his time mentoring pulmonary and critical care fellows, junior faculty and other trainees in patient-oriented research on chronic airway infections. This proposal will enable Dr. Singh to expand his translational research program, integrate fellows and junior faculty in to the program, and provide protected time so that the can mentor additional MD fellows. The proposal also provides time and infrastructure to help Dr. Singh enhance his own mentoring skills. The two research projects described involve face-to-face interactions with patients Project 1 exploits preliminary findings which show that infecting P. aeruginosa strains evolve to produce genetically diverse but clonally-related populations within CF lungs, and that the relative abundance of subpopulations change as patients are treated with antibiotics. This is important because subpopulations that increase during treatment have phenotypes that enable them to resist treatment in vivo, while those that decrease lack resistance functions. Studying these subpopulations enable us to test novel hypotheses about the mechanisms enabling bacteria to withstand antibiotics in chronic infections. Project 2 exploits preliminary findings that show that upper airway contamination may confound DNA-based measurements of lung microbiota. Accurately identifying the bacteria causing CF infections is among the most important tasks in CF infection research. We propose using the novel 2-scope method, along with advanced analytic methods, to test the hypotheses that some of the taxa identified in upper airway samples from CF children using DNA-based methods are oropharyngeal contaminants, or are derived from non viable cells.
The goal of this K24 is to provide salary support for Dr. Singh to allow him to spend 40% of his time mentoring pulmonary and critical care fellows, junior faculty and other trainees in patient-oriented research on chronic airway infections. This proposal will allow Dr. Singh to expand his translational research program, integrate fellows and junior faculty into the program, and provide protected time so that he can mentor additional MD fellows. The project also supports research on the treatment and pathogenesis of chronic lung infections.
|Secor, Patrick R; Michaels, Lia A; Ratjen, Anina et al. (2018) Entropically driven aggregation of bacteria by host polymers promotes antibiotic tolerance in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 115:10780-10785|
|Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher et al. (2017) Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections. Am J Respir Crit Care Med 195:1617-1628|
|Adam, Ryan J; Hisert, Katherine B; Dodd, Jonathan D et al. (2016) Acute administration of ivacaftor to people with cystic fibrosis and aG551D-CFTRmutation reveals smooth muscle abnormalities. JCI Insight 1:e86183|
|Kapnadak, Siddhartha G; Hisert, Katherine B; Pottinger, Paul S et al. (2016) Infection control strategies that successfully controlled an outbreak of Mycobacterium abscessus at a cystic fibrosis center. Am J Infect Control 44:154-9|
|Hmelo, Laura R; Borlee, Bradley R; Almblad, Henrik et al. (2015) Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange. Nat Protoc 10:1820-41|
|Wu, Xia; Held, Kiara; Zheng, Chunxiang et al. (2015) Dynamic Proteome Response of Pseudomonas aeruginosa to Tobramycin Antibiotic Treatment. Mol Cell Proteomics 14:2126-37|
|Jorth, Peter; Staudinger, Benjamin J; Wu, Xia et al. (2015) Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs. Cell Host Microbe 18:307-19|
|Secor, Patrick R; Sweere, Johanna M; Michaels, Lia A et al. (2015) Filamentous Bacteriophage Promote Biofilm Assembly and Function. Cell Host Microbe 18:549-59|
|Navare, Arti T; Chavez, Juan D; Zheng, Chunxiang et al. (2015) Probing the protein interaction network of Pseudomonas aeruginosa cells by chemical cross-linking mass spectrometry. Structure 23:762-73|
|Schweppe, Devin K; Harding, Christopher; Chavez, Juan D et al. (2015) Host-Microbe Protein Interactions during Bacterial Infection. Chem Biol 22:1521-1530|
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