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), 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:

Dab2 Inhibitors as Therapeutic Stabilizers of F508-CFTR

Project Leader: Dean Madden, Ph.D.

Microbiological profiles in sputum and in regions of airway damage

Project Leader: Alix Ashare, M.D., Ph.D.
Co-Investigator: Deborah A. Hogan, Ph.D.

Arsenic exposure and airway remodeling after acute influenza infection

Project Leader: Mitsuo Matsuoka, MD, Ph.D.
Co-Investigator: Richard I. Enelow, M.D.

Optimization of a novel compound with activity against MRSA and P. aeruginosa

Project Leader: Ambrose Cheung, M.D.

Development of cFLIP-calmodulin interaction inhibitors for lung cancer therapy

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

Novel molecular methods for the analysis of cystic fibrosis (CF) sputum

Project Leader: Joseph Schwartzman, M.D.
Co-Investigator: Deborah A. Hogan, Ph.D.

The longitudinal microbiology and immunology of the airway in mechanically ventilated adults

Project Leader: Manuel Vilchez, M.D.
Co-Investigators: Richard Zuckerman, M.D., M.P.H., Harold Manning, M.D., George A O'Toole, Ph.D.

Regulation of the Fungal Hypoxia Virulence Factor SrbA

Project Leader: Robert A. Cramer, Ph.D.

Autoimmunity and Lung Function in Cystic Fibrosis

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

Linking Pulmonary Acidosis to Inflammation

Project Leader: Brent Berwin, Ph.D.

News

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 article in Chemistry and Biology can be accessed with this link until July 10. The PubMed link will be available at a future date.

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.

Researcher Alex Gifford Publishes Paper on Updated Survival Projection for CF Patients

April 2015

The paper Longevity of Patients with Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry was based on data in the U.S. Cystic Fibrosis Foundation Patient Registry. It was published last fall in the Annals of Internal Medicine.

Researchers Jane Hill & Alix Ashare Receive SYNERGY Pilot Award

April 2015

Researchers Jane E. Hill, PhD (PI, Engineering/Thayer) and Alix Ashare, MD, PhD (Co-PI, Medicine) recently received a SYNERGY Translational Pilot Award for the project “Biomarker Discovery and Validation for Lung Infection in CF patients”. Their project was one of eight awards made out of a total of 24 full applications that were submitted. For additional information, please see Geisel Insider.

Laura Filkins Accepted Into Postdoctoral Fellowship

April 2015

Laura Filkins, a Ph.D. student in the O'Toole Lab, has been accepted into a very competitive Medical Microbiology fellowship at the Department of Pathology, University of Utah School of Medicine and ARUP Laboratories. Please see O'Toole Lab News for additional information.

8th Annual Integrative Biology Symposium on "Epigenetics" Held at Dartmouth College

April 2015

The April 21-22 symposium on epigenetics explored how environmental factors affect gene expression and the characteristics of organisms. Click here for the agenda.

Madan and Hoen Lab Findings on Airway Health

April 2015

In a recent collaborative study with collegaues at Dartmouth, led by Juliette Madan (in the Dept. of Pediatrics) and Annie Hoen (in the Dept. of Epidemiology), the O'Toole Lab investigated the upper airway and gut microflora of infants and children with CF. This group of children ranged up to almost 3 years of age. In their report, the research team demonstrates a link between the microflora in the gut and respiratory health. In particular, the researchers show an association between gut microbiota and initial Pseudomonas aeruginosa colonization and onset of exacerbation. This exciting finding suggests that oral probiotics have the potential to impact airway health. The paper Associations between Gut Microbial Colonization in Early Life and Respiratory Outcomes in Cystic Fibrosis recently was published online in the Journal of Pediatrics. A commentary by Leopoldo Segal and Martin Blaser will accompany the publication of the article in the Journal of Pediatrics.

Lung Biology Center 2015 Pilot Awards

April 2015

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 27, 2015. For details, please see RFA announcement.

3rd Annual Cystic Fibrosis Retreat Held at Geisel School of Medicine

March 2015

Over 100 Cystic Fibrosis (CF) researchers from New England attended the 3rd annual Cystic Fibrosis Retreat at the Geisel School of Medicine at Dartmouth College on March 10, 2015. Twelve invited speakers presented a variety of talks on CF drug discovery, bacterial infections and inflammation in CF.

Karl Griswold Group Publishes Articles on Antibacterial Enzymes

February 2015

Karl Griswold and his students recently published a series of articles on developmental antibacterial enzymes. These articles describe two advances: 1. Designing human lysozyme variants that evade inhibitory proteins produced by bacterial pathogens. 2. Engineering S. aureus's own cell wall recycling machinery so as to render these endogenous enzymes potent antibacterial agents.

Links to the three articles:

Click here to read article.
Click here to read article.
Click here to read article.

Laura Filkins Receives Travel Grant, Presents Poster

February 2015

Laura Filkins, a PhD student in the O'Toole lab, received a $500 travel grant for the ASM Conference on Polymicrobial Infections. Laura presented a poster at the meeting titled "Dynamic P. aeruginosa-S. aureus inter-bacterial interactions impact community composition and s. aureus survival in the respiratory tract of patients with cystic fibrosis".

Small Fish Provide Major Insight into How Organisms Adapt to Change

February 2015

A team of scientists that includes Lung Biology Center investigators Bruce Stanton and Thomas Hampton have identified the genes and regulatory networks that enable organisms to alter themselves physically in response to changes in their environment. The paper was published in the journal Molecular Biology and Evolution and was named one of the “papers of the month” by the National Institute of Environmental Health Sciences. See full story.

Events

Weekly Lung Biology Seminar Series Sponsored by Lung Biology Center

Please click here to view the weekly schedule.

Introduction to Applied Bioinformatics Course at MDIBL

August 1-6, 2015

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 using CLC Genomics Workbench and 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.