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.


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, 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.

Results of Tour de Force Project Published

May 2015

A collaborative effort between Dartmouth lung biology (including Karl E. Griswold) and computer science researchers has produced novel antibacterial enzymes for treatment of multidrug-resistant S. aureus infections. The team used advanced protein design algorithms to generate “deimmunized” variants of the potent anti-staphylococcal enzyme lysostaphin. The engineered enzymes suppressed anti-drug antibody responses in humanized HLA-transgenic mice, and as a result the modified enzymes outperformed the wild type control by rescuing mice from recurrent challenges with a MRSA clinical isolate. This is the first direct and controlled demonstration that T cell epitope deletion in protein therapeutics manifests enhanced in vivo efficacy. The paper Depletion of T Cell Epitopes in Lysostaphin Mitigates Anti-Drug Antibody Response and Enhances Antibacterial Efficacy In Vivo has published in Chemistry and Biology .

Coverage of the research has included:

C&EN Chemistry and Engineering News
ACS Noteworthy Chemistry
BioCentury Innovations
Dartmouth Now
Dartmouth Engineer Magazine
and VT Public Radio (VPR)

Great Strides Walk Raises Over $15,000 for CF Research

May 2015

On Saturday, May 2nd, over sixty walkers and runners, including Dartmouth researchers, clinicians and CF families, participated in the Cystic Fibrosis Foundation Great Strides Walk at Storrs Pond in Hanover. Great Strides is the CF Foundation's largest nationwide fund raising event and this year the Hanover walk raised over $15,000 for CF research and drug development! The event began with a moving speech from Chris Ross, a sailor, husband and adult with CF. He shared personal story of living with CF and his intentions to be the first person with CF to sail around the globe. The Dartmouth Lung Biology Team was recognized as a Top Team, raising over $3000 for CF research. Representatives from Vertex and Novartis were recognized for their generous support of Great Strides. Participants enjoyed snacks from Lebanon Health Food Store and Moe's after a 3 mile trek through the Storrs Pond hiking trails. The walk was organized by Deb Hogan, Katie Price, Kelli Hvorecny, Sharon Littlefield, Jessie Scott and Lindsay Gilbert.

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Weekly Lung Biology Seminar Series Sponsored by Lung Biology Center

Please click here to view the weekly schedule.