This COBRE III application requests funding to complete the establishment of a free standing, nationally recognized Lung Biology Center (LBC) in the Geisel School of Medicine at Dartmouth. The proposed plan for COBRE III builds upon our successes during COBRE I and II during which time we assembled, from a nucleus of 6 faculty, a critical mass of 32 well funded, tenured and tenure-track principal investigators who conduct inter-/multi-disciplinary research on respiratory infectious diseases. Our LBC faculty share common interests in host-pathogen interactions, the respiratory microbiome, and in drug discovery and therapeutic development. To support the research of our faculty we established three LBC-specific research cores, including a: (1) Host-Pathogen Interaction Core, (2) Live-Cell Imaging Core and (3) Translational Research Core. All of our junior faculty project leaders in COBRE 1/11 have already obtained extramural funding, an impressive record of accomplishment in this funding environment. A COBRE III award will provide essential resources to facilitate the continued development ofthe LBC, provide vital resources to enhance inter/multidisciplinary basic science and translational research in respiratory infectious disease, and is an essential component of our research core business plan to be financially independent by 2018. COBRE III support will enhance the continued mentored development of our junior faculty, including those previously supported by COBRE l/ll, the expansion ofthe research cores and an enhanced Pilot Project Program, and will facilitate mentored, collaborative and/or translational research at Dartmouth. Together with a substantial, and longterm, commitment from Dartmouth and strong collaborative ties with investigators in the Lung Biology and Immunology COBRE programs at the University of Vermont (UVM), the Dartmouth Immunology COBRE, the Dartmouth Quantitative Biological Sciences COBRE, and the INBRE programs at UVM, Dartmouth and the Mt. Desert Island Biological Laboratory (MDIBL) in Maine, we are in an exceptionally strong position to continue to build upon our successes in research on host-pathogen interactions, the respiratory microbiome in CF, and in drug discovery and therapeutic development for respiratory infectious diseases.
Infectious respiratory diseases are the third leading cause of death in the U.S. The studies described in this application will lead to a better understanding of how opportunistic pathogens, including Pseudomonas aeruginosa, cause chronic respiratory infections, and to new drugs / therapies to treat infectious respiratory disease.
|Amacher, Jeanine F; Zhao, Ruizhi; Spaller, Mark R et al. (2014) Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ domain. PLoS One 9:e103650|
|Cheng, Shih-Chin; Quintin, Jessica; Cramer, Robert A et al. (2014) mTOR- and HIF-1?-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684|
|Chen, Annie I; Dolben, Emily F; Okegbe, Chinweike et al. (2014) Candida albicans ethanol stimulates Pseudomonas aeruginosa WspR-controlled biofilm formation as part of a cyclic relationship involving phenazines. PLoS Pathog 10:e1004480|
|Torres, Iviana M; Patankar, Yash R; Shabaneh, Tamer B et al. (2014) Acidosis potentiates the host proinflammatory interleukin-1? response to Pseudomonas aeruginosa infection. Infect Immun 82:4689-97|
|Chung, Dawoon; Barker, Bridget M; Carey, Charles C et al. (2014) ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence. PLoS Pathog 10:e1004487|
|Chung, Dawoon; Thammahong, Arsa; Shepardson, Kelly M et al. (2014) Endoplasmic reticulum localized PerA is required for cell wall integrity, azole drug resistance, and virulence in Aspergillus fumigatus. Mol Microbiol 92:1279-98|
|Jackson, Angelyca A; Daniels, Emily F; Hammond, John H et al. (2014) Global regulator Anr represses PlcH phospholipase activity in Pseudomonas aeruginosa when oxygen is limiting. Microbiology 160:2215-25|
|Shepardson, Kelly M; Jhingran, Anupam; Caffrey, Alayna et al. (2014) Myeloid derived hypoxia inducible factor 1-alpha is required for protection against pulmonary Aspergillus fumigatus infection. PLoS Pathog 10:e1004378|