The overarching goal of this application is to complete the establishment of a thriving, stand-alone Lung Biology Center (LBC) of Biomedical Research Excellence at Dartmouth, and thus to advance the understanding and treatment of lung disease. We have recruited a critical mass of faculty investigators with strong track-records of scientific productivity and extramural funding. To sustain a trajectory of novel, highimpact, multi-disciplinary and translational research projects, our Pilot Project Program (P^) will: 1) Encourage the development of preliminary data to open up new research opportunities, refine hypotheses, and strengthen proposals to compete for extramural support;2) Enhance collaborative and interdisciplinary research, engaging current LBC members and recruiting additional faculty at Dartmouth and our IDeA partners;3) Deepen our reservoir of translational and clinical research projects, providing funds to physician scientists and their collaborators;4) Nucleate the submission of multi-investigator center and programproject grants;and 5) Support the professional development of our faculty through mentoring of junior faculty and physician scientists. Under COBRE II, we leveraged $377K of pilot support into $6.2M of extramural funding. Building on this model, have designed an inclusive RFA and a rigorous multi-stage review procedure to award P^ grants under three mechanisms: 1) Mentored Basic or Translational Studies for junior faculty;2) Collaborative Basic or Translational Studies for interdisciplinary studies;and 3) Translational and Clinical Studies, led by an MD or MD/PhD faculty investigator. Administrative Core supervision will assure compliance with NIH and institutional rules and provide comprehensive evaluation of each project and ofthe Program as a whole. The P^ awards will accelerate the pace of research and support the intellectual vitality and self-renewal of the LBC. They will also foster interdisciplinary, multi-investigator, and clinically relevant research. Thus, the P Program is closely aligned with COBRE, IDeA, and NIH objectives. By engaging existing and new faculty and supporting transformative research, it will directly enhance the identity and scientific impact of the Dartmouth Lung Biology Center.
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|