COBRE Center for Lung Biology Research

Lung disease is the third most frequent cause of death in this country, claiming ~360,000 Americans annually. Tragically, an additional 25 million live with chronic lung diseases, including asthma, emphysema, cancer and cystic fibrosis. Unfortunately, the number of individuals with lung disease is increasing at an alarming rate, thus, a better understanding of the etiology of lung disease and new therapeutics to treat lung disease are required.

The goals of the Dartmouth Lung Biology Center, funded by a COBRE award by the NCRR and NIGMS since 2003 (P20-RR018787/GM103413 and P30-GM106394), and funding from the CF Research Development Program (CFRDP) are to enhance the research efforts of our faculty and students by:

  1. Integration of the COBRE supported Cores (Host Pathogen Integration Core, Live Cell Imaging Core, and Translational Research Core) with shared services in the Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center(DHMC) and other IDeA supported Cores, including Bioinformatics and Biostatistics;

  2. Fostering synergistic scientific collaboration through the COBRE Research Projects, associated Cores, and other basic and translational infrastructure and programs at the Geisel School of Medicine at Dartmouth/DHMC, including the Immunology COBRE, the Bioinformatics COBRE, the Center for Epidemiology COBRE, and the Dartmouth INBRE programs;

  3. Mentoring and supporting the career development of all faculty in the program, and;

  4. Providing administrative support.

Pilot Projects:

Systems-Level Analysis of P. aeruginosa Response to Antibiotics with ADAGE

Project Leader: Deborah A. Hogan, Ph.D.

Respiratory Virus Infection and Pseudomonas Virulence in Cystic Fibrosis

Project Leader: Richard I. Enelow, M.D.
Co-Investigator: Peter Wright, M.D.

Mechanisms of Regional Heterogeneity of Lung Macrophage Inflammation

Project Leader: Alix Ashare, M.D., Ph.D.

Development of cFLIP-Calmodulin Interaction Inhibitors for Lung Cancer Therapy

Project Leader: Maria Pellegrini, Ph.D.
Co-Investigator: Dale F. Mierke, Ph.D.

Microbial Activity as a Determinant of Health Status in Cystic Fibrosis

Project Leader: Alex H. Gifford, M.D.

Promoting the Phagocytic Clearance of Non-Motile P. Aeruginosa

Project Leader: Brent Berwin, Ph.D.
Co-Investigator: Scott Gerber, Ph.D.

A Novel Murine Model of Allergic Bronchopulmonary Aspergillosis

Project Leader: Robert A. Cramer, Ph.D.
Co-Investigator: Joshua J. Obar, Ph.D.

Monitoring Efforts to Clear P. aeruginosain Cystic Fibrosis Patients

Project Leader: Jane Hill, Ph.D.

Linking Disease Outcomes to the Gut Microbiota in Infants and Children with CF

Project Leader: Todd A. MacKenzie, Ph.D.
Co-Investigators: Juliette Madan, M.D., M.S.; George A. O'Toole, Ph.D



Dr. Dean Madden Appointed Dartmouth Vice Provost for Research

December 2016

Dr. Dean Madden, Dartmouth Lung Biology Center Researcher and Biochemistry and Cell Biology Professor, has been appointed to the position of Vice Provost for Research by Dartmouth Provost Carolyn Dever. In this position, Professor Madden will oversee Dartmouth's research vision, strategy, and infrastructure and work with the provost on strategic planning efforts. According to Dr. Madden, his goal is to "encourage new research initiatives while administering institutional requirements in a way that minimizes barriers to the work." He currently leads a Dartmouth biomedical laboratory that conducts National Institutes of Health-funded research projects on molecular recognition and cystic fibrosis, and directs the newly established campus-wide Institute for Biomolecular Targeting. He will continue to teach and pursue his research interests while serving the four-term in the provost's office. See full story.

Patrick Marshall Speaks at October 19 Lung Biology Meeting

October 2016

Patrick Marshall, Chief Business Officer and co-founder of Stratacuity, spoke at Dartmouth"s Lung Biology Seminar Series on "My Audacity of HOPE: What 17 years as a CF-Dad/caregiver, rare disease advocate & biopharmaceutical insider as taught me". Patrick shared his family's wins and losses, his perspective on the power of HOPE, his outlook for CF science (including his biggest concerns) and on why urgency matters.

Researcher Ali Ashare Publishes Paper in PLoS ONE

October 2016

The paper, Throat Swabs and Sputum Culture as Predictors of P. aeruginosa or S. aureus Lung Colonization in Adult Cystic Fibrosis Patients, which was recently published in PLoS ONE, investigates the utility of throat swab cultures in detecting the most common CF pathogens. Dr. Alix Ashare, along with Pulmonary Fellow Dr. Darius Seidler and other Lung Biology Center colleauges, compared culture results of two of the most common CF pathogens obtained from throat swabs, sputum, and bronchoalveolar lavage fluid obtained from adult patients with CF. Their work demonstrates that the positive predictive value of P. aeruginosa when found on throat swab is excellent, but S. aureus on throat swab was not a good predictor of S. aureus in the lung. These data suggest that throat culture results in adult patients with CF need to be interpreted within the clinical context and may not reflect colonization of the lung.

Researcher Robert Cramer Publishes Paper in ASM Journal mBio

October 2016

The paper, Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with Aspergillus fumigatus Virulence, recently published in the ASM journal mBio, highlights the role of intraspecies heterogeneity in the important pulmonary fungal pathogen Aspergillus fumigatus in the specific host context of corticosteroid-mediated immune suppression. Dr. Robert Cramer, and his students and colleagues, report that A. fumigatus virulence, specifically in this host context, varies across clinical and environmental isolates, and that this variation correlates significantly with the ability of the strains to thrive in low oxygen (hypoxia), a known and prominent feature of the in vivo host microenvironment in this model. An experimental evolution approach through hypoxic conditions was utilized to illustrate this relationship between hypoxic fitness and virulence in this pathogen, and the authors' work to identify the precise causative mechanisms coordinating this relationship remain ongoing. Importantly, this report highlights the existence of clinically-relevant heterogeneity within the single pathogenic fungal species A. fumigatus, and further emphasizes the noteworthy differences in fungal virulence across different host contexts.

New COBRE Award for Biomolecular Targeting

August 2016

Dartmouth has received a five-year, $12.5M National Institutes of Health (NIH) award to establish a new COBRE Institute for Biomolecular Targeting. The Institute is led by Lung Biology Center faculty members Dr. Dean Madden (PI/Director) and Dr. Deborah Hogan (Associate Director). The proposal highlighted four junior-faculty research programs focused on discovery and early-stage translational studies to identify new molecular targets for cancer, inflammation, and viral airway infections. The inflammation studies, spearheaded by Translational Research Core Co-Director Dr. Alix Ashare, have already received independent NIH funding. iTarget also funds shared scientific resources for producing molecular tools (proteins and small molecules) and for analyzing their interactions in vitro and in cells. The Institute also coordinates programs for mentoring, training, and pilot studies. It joins an interactive group of COBRE and INBRE Programs at Dartmouth and across the region. Dartmouth News story.

Applied Bioinformatics Course Held July 23-28 at MDI Biological Laboratory

July 2016

The Applied Bioinformatics Course, which was co-directed by Dartmouth Lung Biology Center Director Dr. Bruce Stanton, provided hands-on training with major bioinformatics resources while developing a conceptual framework to foster successful application of the bioinformatic skillset to biological research. Topics covered included web-based gene and protein resources, genome browsers, DNA and RNA-Seq data analysis, the R statistical computing environment, Ingenuity® pathway analysis, gene set enrichment analyses and machine learning applications. More information can be found at the course web site.

The course organizers greatly appreciate funding from The Geisel School of Medicine at Dartmouth (Lung Biology Center of Biomedical Research Excellence and the Dartmouth Institute for Quantitative Biomedical Sciences) and the Maine IDeA Network for Biomedical Research Excellence.

Dr. Alex Gifford Selected for 2016 Cystic Fibrosis Foundation PACE Award

July 2016

Dartmouth Lung Biology Center researcher Dr. Alex Gifford has been chosen to participate in the Program for Adult Care Excellence (PACE) by the Cystic Fibrosis Foundation. The PACE initiative is designed to expand the scope of adult care programs and increase the number of adult caregivers who understand the health problems and needs of this population. The award will enable Dr. Gifford to continue his career development as a clinician-scientist in the Dartmouth community over the next three years. Dr. Gifford joins Dr. Alix Ashare, Director of the New Hampshire Cystic Fibrosis Center and Dartmouth Lung Biology Center researcher, as a local recipient of the PACE Award.

Dr. Deborah Hogan Selected as 2016 COBRE Independence Award Recipient

June 2016

Dartmouth Lung Biology Center researcher Dr. Deborah Hogan has been selected as the 2016 COBRE Independence Award recipient by the National IDeA Symposium of Biomedical Research (NISBRE) Awards Committee. Professor Hogan has been recognized for her research, teaching, service, and mentorship excellence at Dartmouth. The COBRE Independence Award was established in 2006 to honor Dr. Thomas Maciag, an internationally recognized cell and vascular biologist. It honors individuals who exemplify his ideals of research excellence and commitment to mentoring, and who have established independence through a COBRE program. Dr. Hogan will be recognized as the 2016 COBRE Mentoring Awardee at the 2016 NISBRE June 26-28 meeting and will give an oral presentation. Click here for Geisel Insider story on Dr. Hogan's receipt of the award and her accomplishments.

Great Strides Walk Raises Over $12,700 for CF Research

May 2016

Together, friends and family of Cystic Fibrosis patients, CF researchers, and DHMC staff raised over $12,700 for the Hanover 2016 Great Strides for Cystic Fibrosis event. The walk was kicked off by a beautiful speech by Meghan, who reminded us why our fundraising and support is important and how research funded by the Cystic Fibrosis Foundation positively impacted her life. Walkers enjoyed refreshments generously donated by Lou's, Dazzle Cupcakes, and Moe's. All funds donated to the Cystic Fibrosis Foundation support research for drug development and a cure to this devastating disease. We look forward to seeing everyone at next year's Great Strides event!

Literature Review Published by Dr. Juliette Madan

April 2016

Dr. Juliette Madan, Division of Pediatrics, Geisel School of Medicine at Dartmouth, has published a literature review, "Neonatal gastrointestinal and respiratory microbiome in cystic fibrosis: potential interactions and implications for systemic health". Click here for link to the article. The review also was highlighted on the MDLinx website.

6th Annual Cystic Fibrosis Retreat Held at Dartmouth

March 2016

The 6th annual Dartmouth Cystic Fibrosis Retreat was held on March 22 at the Hanover Inn in Hanover, NH. More than 100 people attended. The goal of the retreat is to bring together basic- and physician-scientists with clinicians and with members of pharma and biotech to talk about all aspects of science and care related to CF. This is a regional meeting drawing investigators from across New England. The Dartmouth CF retreat was generously sponsored by Vertex Pharmaceuticals.

Lung Biology Center 2016 Pilot Awards

March 2016

The Dartmouth Lung Biology Center requests applications for Pilot Project Program (P^3) Awards. We seek to fund basic, translational, and clinical research that will advance the understanding and treatment of lung disease, strengthen interdisciplinary faculty interactions, and leverage extramural funding opportunities. Deadline: April 8, 2016. For details, please see the RFA 2016 announcement.

$15 Million Gift to the Dartmouth Cystic Fibrosis Research Program

January 2016

A generous donor has given $15 million to the Dartmouth CF Research Program to increase Dartmouth's expertise in systems biology, bioinformatics, and microbial pathogenesis in CF. According to Bruce A. Stanton, Ph.D., Director of the CF Research Program at Dartmouth, "This magnanimous gift to our CF Research Program will strengthen, intensify and expand our research efforts to identify personalized cures for every CF patient. The generosity of this donor will benefit generations and generations of people who live with CF every day.” With this gift, Dartmouth has the opportunity to take CF research and treatment to levels undreamed of even a decade ago. Because the disease is unique for each patient, there is a growing emphasis on developing innovative, personalized treatments. Dartmouth will create a research program with the ambitious goal of developing novel therapeutics for all cystic fibrosis patients and eliminating fungal and bacterial lung infections. For more information on the gift, see coverage in Dartmouth Now and the Geisel News Center.

New Machine-Learning Technique Can be Applied to Study of Pseudomonas aeruginosa

January 2016

There are now vast quantities of data that are uploaded and made available but rarely used. A collaboration between Deborah Hogan, Associate Professor in Microbiology and Immunology and Dartmouth Lung Biology Center Researcher and Casey Greene, Assistant Professor at the University of Pennsylvania and a former Dartmouth Lung Biology Center Researcher, developed a method to make these data useful to researchers. Their application of this method to the study of Pseudomonas aeruginosa, a major challenge for individuals with Cystic Fibrosis, has been published in the journal mSystems. For more information, see Penn Medicine News Release and the paper ADAGE-Based Integration of Publicly Available Pseudomonas aeruginosa Gene Expression Data with Denoising Autoencoders Illuminates Microbe-Host Interactions.

A Microbiome is Borne - Science Friday

January 2016

"A baby in the womb is protected from most microorganisms. But when that baby enters the outside world, it's greeted by a welcoming committee of bacteria. Now, researchers are trying to sort out what effect factors like an infant's delivery method and early diet have on its community of microorganisms. Juliette Madan and Anne Hoen, two authors of a paper published recently in the journal JAMA Pediatrics, say that developing a better understanding of the infant microbiome could one day lead to healthier babies." Click here for more information on "A Microbiome is Born".

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Weekly Lung Biology Seminar Series Sponsored by Lung Biology Center

Please click here to view the weekly schedule.

Hanover Great Strides Walk for Cystic Fibrosis to be Held May 13, 2017

The Hanover Great Strides fundraising walk for CF Research will be on May 13th, 2017. Check in will be at 10am and the walk will start at 10:30am at the Storrs Pond Pagoda in Hanover, NH. Walkers should wear comfortable shoes. The route will be an easy 5k hike around the Storrs Pond trails. There is no minimum donation to register to walk and registration will open online at in the spring of 2017.