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 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.

Autoimmunity and Lung Function in Cystic Fibrosis

Project Leader: William F.C. Rigby, M.D.

Linking Pulmonary Acidosis to Inflamamation

Project Leader: Brent Berwin, Ph.D.

News

2016

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".

2015

Researcher Alex Gifford and Colleagues Publish Paper on Association Between Serum Iron Measurement and Pulmonary Exacerbation by CF Patients

December 2015

The paper, Serum Iron Level Is Associated with Time to Antibiotics in Cystic Fibrosis, highlights the efforts of the CF Translational Research Core over the past several years. Dartmouth SYNERGY Scholar, Dr. Alex Gifford, and his colleagues report in the journal Clinical and Translational Science that a one-time serum iron measurement is helpful in predicting the time it takes patients with cystic fibrosis (CF) to subsequently experience a pulmonary exacerbation. Using multivariate regression models, the investigators found that lower serum iron concentration, younger age, and sputum culture positivity for Aspergillus species were independently associated with a shorter time to next exacerbation, defined as a need for treatment with systemic antibiotics due to health deterioration.

Researchers Dale Mierke and Maria Pellegrini Publish Paper on cFLIP Inhibitory Protein and Calmodulin

November 2015

The paper Identification and Characterization of the Interaction Site between cFLIPL and Calmodulin results from the researchers' COBRE Pilot Project "Development of cFLIP-calmodulin interaction inhibitors for lung cancer therapy". It was published in PLoS ONE. The Pilot focuses on the characterization of protein-protein interactions and their modulation through design and synthesis of peptide and small molecular weight inhibitors.

Professor Dale Mierke Named Frank R. Mori Chair of Arts and Sciences

October 2015

Dr. Dale Mierke, Dartmouth College Professor and Dartmouth Lung Biology Center Researcher, recently has been named as the Frank R. Mori Chair of Arts and Sciences for his teaching and research efforts in Chemistry. His laboratory employs nuclear magnetic resonance (NMR) techniques for the structural characterization of proteins to assist in the rational design of molecules to bind and inhibit the biological activity of the target. The NMR facility specifically is set up for the screening of compound libraries. The laboratory is currently investigating inhibitors of FLIP, a molecule upregulated in lung cancer, that leads to cell proliferation, particularly when challenged with chemotherapy. Additional information can be found in Dartmouth Now.

Introduction to Applied Bioinformatics Course at MDIBL (August 1-6, 2015)

August 2015

The Applied Bioinformatics Course, co-sponsored by MDI Biological Laboratory and the Dartmouth Lung Biology Center, provided hands-on training for faculty, postdoctoral fellows and graduate students to develop a conceptual framework to foster successful application of the bioinformatic skillset to biological research. Course participants focused on analysis of high throughput sequencing data to identify differentially expressed genes, investigated biological functions, and predicted interaction networks. Topics covered included web-based gene and protein resources, genome browsers, DNA and RNA-Seq data analysis using CLC Genomics Workbench and the R statistical computing environment, Ingenuity® pathway analysis, gene set enrichment analyses and machine learning applications.

Researcher and Group of Doctors Challenge Vertex on Price of Cystic Fibrosis Drug

July 2015

Almost three weeks after Vertex Pharmaceuticals Inc. won US approval for a combination therapy called Orkambi that eventually may treat roughly half of the 30,000 Americans with cystic fibrosis, a California researcher and several doctors who treat CF are going public with their objection to its annual price of $259,000 per patient. The story, which appeared on BostonGlobe.com, includes comments by Dr. Brian O'Sullivan, a Professor of Pediatrics at Geisel School of Medicine at Dartmouth and a Pediatric Pulmonologist at Dartmouth-Hitchcock Medical Center.

Lung Biology Researchers Cited For Novel Bioinformatic Approach

June 2015

Biotech giant QIAGEN has recognized recent work in evolutionary biology by Dartmouth Lung Biology Center researchers Bruce Stanton and Tom Hampton, citing their recent publication Natural Selection Canalizes Expression Variation of Environmentally Induced Plasticity-Enabling Genes in Molecular Biology and Evolution. In that work, Dartmouth Superfund researchers identified that phenotypic plasticity in killifish may rely on special gene network structures, an effect revealed during salinity acclimation in the presence of the environmental toxin, arsenic.

More News...

Events

Weekly Lung Biology Seminar Series Sponsored by Lung Biology Center

Please click here to view the weekly schedule.

Applied Bioinformatics Course at MDI Biological Laboratory

July 23-28, 2016

The goal of the Applied Bioinformatics Course is to provide hands-on training with major bioinformatics resources while developing a conceptual framework to foster successful application of the bioinformatic skillset to biological research. We will focus on analysis of high throughput sequencing data to identify differentially expressed genes, investigate biological functions, and predict interaction networks. Topics covered include 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.

The course will feature several modules in which participants will be guided through hands-on use of featured bioinformatic tools and resources to analyze example datasets. Prior experience in bioinformatics is not required and computer programming skills are not required, but participants should have a solid background in molecular biology and a strong interest in learning programming concepts.

More information and the current agenda can be found at the course web site. Tuition, room and board is $905 for students and post-docs, and $1,400 for faculty and industry participants.

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.