Joshua Hamilton, Ph.D., Co-Director

Jay Leiter, M.D., Co-Director

Program Overview

The National Institutes of Health awarded a team of New Hampshire scientists a five-year, $12 million grant to establish an interdisciplinary research center on lung diseases in New Hampshire. The grant will support research at Dartmouth Medical School, Dartmouth College and Keene State College, in collaboration with the state of New Hampshire’s Department of Environmental Services and Department of Health and Human Services. The funding will create the infrastructure to enable Dartmouth (25 investigators in 12 Departments) and Keene State investigators to conduct state-of-the art research on lung disease. Lung disease is the third most frequent cause of death in this country, claiming close to 361,000 Americans annually. Tragically, an additional 25 million live with chronic lung diseases including asthma, emphysema, cancer and cystic fibrosis. Our Program will study the molecular and cellular mechanisms that underlie the initiation, pathogenesis, progression, and treatment of lung disease.

The funding, known by the acronym COBRE (for Centers of Biomedical Research Excellence) was established by NIH to augment and strengthen the biomedical research capabilities of small or rural states to enhance the scientific expertise of junior faculty in those regions.

The Program includes five multidisciplinary research projects that fall under the umbrella of “cellular and molecular mechanisms of lung disease.” The three projects that focus on cystic fibrosis will investigate the biology of the cells affected by the disease, the structure of the molecules involved and the infections that are common in people who have the disorder. Cystic Fibrosis is one of the most common genetic diseases in the US and one in 25 individuals are carriers for the disease. Two other projects will study the environmental factors that contribute to lung cancer, which accounts for 30% of all cancers in New Hampshire, and other lung diseases. Investigators on those projects will work with investigators at Keene State College, and state agencies to examine the effects of agents such as arsenic, radon, and diesel exhaust. Funds will also support the recruitment of three new faculty, and the development of a new, state-of-the-art technical facility in proteomics — the study of proteins. The new proteomics facility at DMS will enable scientists to study the location, structure and function of the proteins involved in these lung diseases.

The COBRE program supports faculty mentoring by pairing junior level faculty with established senior colleagues, establishing training for graduate students and postdoctoral fellows, and development of closer collaborative research ties among the collaborating groups in New Hampshire. Dartmouth faculty will serve as investigators, project leaders and mentors on the program, and Dartmouth and Keene State College junior faculty will head the individual research projects.

Additional support for the Lung Biology Center at Dartmouth is provided by two other grants: an NIH Training grant which provides support for graduate students and postdoctoral fellows, and a Cystic Fibrosis Research Development Program, which funds Pilot Projects to encourage new investigators to enter the CF field. Dr. Stanton is the Principal Investigator of both grants.

COBRE support will achieve the following overall goals:

1. To establish a Lung Biology Center focused on lung injury, cancer, and cystic fibrosis that will become nationally/internationally recognized, free standing, and will consist of an expanded cadre of investigators able to more effectively compete for NIH funding and enhance the NIH grant portfolio in the State of New Hampshire.

2. To expand and develop lung biology research by:

a. Close mentoring and maturation of the four promising junior faculty already at Dartmouth who will serve as the project leaders on four proposed research projects (Drs. O’Toole, Swiatecka-Urban, Madden, and Duell (Shi, Co-PI).

b. Similar mentoring of Dr. Melinda Treadwell at Keene State College, a junior investigator and project leader.

c. Recruiting two new tenure-track faculty with primary appointments at Dartmouth. All new faculty will be funded with COBRE support.

d. Recruitment of one new tenure-track faulty at Keene State College.

e. Encouraging additional recruitments in basic science and clinical departments for tenure-track research positions for which the searches will be designated or re-prioritized to focus on investigators whose research interests will complement the COBRE theme of lung biology.

f. Establishing both an Administrative and Proteomics Core to promote the goals mentioned above.
Investigators and projects are:

• George O’Toole, Ph.D., (Dartmouth Medical School) who will study how bacteria infect the lungs of patients with Cystic Fibrosis;

• Agnieszka Swiatecka-Urban, M.D. (Dartmouth Medical School and Dartmouth Hitchcock Medical Center) who will study how mutations in CFTR, the gene that is mutated in patients with Cystic Fibrosis, cause the disease;

• Dean Madden, Ph.D., (Dartmouth Medical School) who will analyze the structure of proteins that modulate the function of the CFTR protein in the cell;

• Melinda Treadwell , Ph.D. (Keene State College) who will investigate the effects of air pollution in New Hampshire on lung disease, including cancer; and

• Eric Duell, Ph.D., (Dartmouth Medical School) and Xun Shi, Ph.D., (Dartmouth College) who will conduct an environmental epidemiology study of lung cancer in New Hampshire.