2015 News


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

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

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)

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

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

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

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 been 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

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

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

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

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

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

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

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

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

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

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

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.

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