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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Center Core Grants (P30)
Project #
5P30GM106394-05
Application #
9330169
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Facciponte, Dominic N; Bough, Matthew W; Seidler, Darius et al. (2018) Identifying aerosolized cyanobacteria in the human respiratory tract: A proposed mechanism for cyanotoxin-associated diseases. Sci Total Environ 645:1003-1013
Grahl, Nora; Dolben, Emily L; Filkins, Laura M et al. (2018) Profiling of Bacterial and Fungal Microbial Communities in Cystic Fibrosis Sputum Using RNA. mSphere 3:
Hvorecny, Kelli L; Dolben, Emily; Moreau-Marquis, Sophie et al. (2018) An epoxide hydrolase secreted by Pseudomonas aeruginosa decreases mucociliary transport and hinders bacterial clearance from the lung. Am J Physiol Lung Cell Mol Physiol 314:L150-L156
Torres, Iviana M; Patankar, Yash R; Berwin, Brent (2018) Acidosis exacerbates in vivo IL-1-dependent inflammatory responses and neutrophil recruitment during pulmonary Pseudomonas aeruginosa infection. Am J Physiol Lung Cell Mol Physiol 314:L225-L235
Dhingra, Sourabh; Buckey, Jay C; Cramer, Robert A (2018) Hyperbaric Oxygen Reduces Aspergillus fumigatus Proliferation In Vitro and Influences In Vivo Disease Outcomes. Antimicrob Agents Chemother 62:
Ries, Laure Nicolas Annick; Beattie, Sarah; Cramer, Robert A et al. (2018) Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi. Mol Microbiol 107:277-297
Beattie, Sarah R; Mark, Kenneth M K; Thammahong, Arsa et al. (2017) Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression. PLoS Pathog 13:e1006340
Stanton, Bruce A (2017) Effects ofPseudomonas aeruginosaon CFTR chloride secretion and the host immune response. Am J Physiol Cell Physiol 312:C357-C366
Hvorecny, Kelli L; Bahl, Christopher D; Kitamura, Seiya et al. (2017) Active-Site Flexibility and Substrate Specificity in a Bacterial Virulence Factor: Crystallographic Snapshots of an Epoxide Hydrolase. Structure 25:697-707.e4
Bertrand, Carol A; Mitra, Shalini; Mishra, Sanjay K et al. (2017) The CFTR trafficking mutation F508del inhibits the constitutive activity of SLC26A9. Am J Physiol Lung Cell Mol Physiol 312:L912-L925

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