The overarching goal of the Dartmouth Cystic Fibrosis Research Center (DartCF), funded by NIH NIDDK (P30DK117469), is to build on our strong history of CF-related research in lung infection, inflammation/immunity and translational science, by expanding our capability to investigate host-microbe interactions in the gut, and their impact on gut dysbiosis and overall systemic health of CF-related diabetes patients.
Dartmouth has developed a collaborative, multi-disciplinary research program focused on the airway epithelium and lung infection. Our labs have been pursuing a range of topics including CFTR intracellular trafficking and regulation, airway bacterial colonization, biofilm formation, microbial signaling and adaptation, and therapeutic strategies, including development of new modulator and antimicrobial lead compounds.
Our group has evolved over the last 20 years from a handful of faculty. In 1997 Dartmouth held a single NIH research-project award related to cystic fibrosis (R01DK045881 to Dr. Bruce Stanton). However, in the late 1990s the Cystic Fibrosis Foundation awarded Dr. Stanton a Research Development Program (RDP), intrigued by a nucleus of faculty working in infectious disease (e.g., Host-Microbe Interactions T32AI007519) and epithelial biology (e.g., Renal, later Epithelial, Biology Training Grant T32DK007301), and by the comparative outcomes approaches of emeritus Professor Dr. Gerald O’Connor at The Dartmouth Institute for Health Policy and Clinical Practice. Pilot project funds from the RDP, access to reagents and expertise through the associated Core facilities, and the development of a dynamic research community through weekly seminars and a growing set of collaborations, all supported research transitions into CF-relevant areas for a group of faculty, including Drs. Madden, Hogan and O’Toole. Together this group formed the nucleus of an NIH Institutional Development Award (IDeA) Center of Biomedical Research Excellence (COBRE) grant that established a Lung Biology Center at Dartmouth in 2003 which focused on CF-related lung disease, as a majority of patients succumb to respiratory failure resulting from the chronic infection and inflammation that results from CFTR dysfunction. DartCF has allowed us to expand this group to include basic and clinical faculty with the skills and interest to explore CF-related diabetes, liver disease, pancreatitis, and intestinal microflora combined with efforts to study CF from a systems perspective.
In addition to funding pilot and feasibility awards to develop new research and translational opportunities, DartCF funds the following cores:
- Gastrointestinal Biology Core (GIBC): provides access to a comprehensive suite of in vitro and in vivo models to studies interactions between epithelial, immune, and microbial cells in the gut.
- Clinical and Translational Research Core (CTRC): facilitates DartCF human-subjects projects and will collect, curate and deploy clinical samples (blood, urine, and GI tissue, mucus, and microbiota) and associated metadata.
- CF Bioinformatics and Biostatistics Core (CF-BBC): unites CF and data-science researchers studying complex biomedical and clinical data sets.
The Enrichment & Research Administration Core (ERAC) provides scientific leadership supporting all DartCF members as they explore new high-impact research directions. A weekly seminar series and annual Dartmouth CF Retreat facilitate an interactive scientific community.
Finally, the Dartmouth Cystic Fibrosis Training Program (T32 HL134598), directed by Dr. George O’Toole, trains the next generation of scientists by using a disease-based training paradigm focused on CF.