Medical Student Research Fellowship for Summer 2008
Mentor: Christine Kim Garcia, MD/PhD
Room number: NA2.206
Mail Code: 8591
Phone number: 87424
Project title: Familial Pulmonary Fibrosis and Telomerase Dysfunction
Human subjects IRB approved project number (where applicable): 102004-029; 0203-110
Animal subjects IRB approved project number (where applicable):
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
Brief Description of Project:
Idiopathic pulmonary fibrosis (IPF) is the prototype of a group of progressive diseases affecting older adults characterized by irreversible, lung scarring and a life expectancy of 3 years. Successful treatment of IPF will require a better understanding of disease pathogenesis, better tools to detect individuals at-risk for the disease and new targets for therapeutic intervention. A recent clue as to the genetic underpinnings of this disorder came from our identification of mutations in the genes encoding telomerase in a subset of families with autosomal dominant pulmonary fibrosis. This discovery allows for the identification of at-risk individuals and an opportunity to characterize the natural history of IPF in presymptomatic subjects. This summer we will be performing detailed phenotypic characterization of subjects with inherited mutations in telomerase and normal family member controls. We have preliminary evidence that a reduction in the diffusion capacity across the vascular/alveolar interface may predate radiographic changes of pulmonary fibrosis in subjects with inherited mutations in telomerase. We will determine the penetrance of this phenotype, as well as other select cardiovascular, pulmonary and mineral metabolism phenotypes in a larger cohort of subjects. We will also determine if telomere lengths of circulating leukocytes are associated with clinical markers of disease. The approach has the promise of defining clinical phenotypes of this new genetically-defined syndrome of accelerated human aging with the ultimate goal of better detection, prevention and treatment of this lethal disease.
Previous Research Activities or Publications with Medical Students:
Randall Graham, Summer 2007
Phillip Kuan, Doris Duke student, 2005-2006
Tsakiri, K.D., Cronkhite, J.T., Kuan, P.J., Xing, C., Raghu, G., Weissler, J.C., Rosenblatt, R.L., Shay, J.W., and Garcia, C.K. (2007) Adult-Onset Pulmonary Fibrosis Caused by Mutations in Telomerase. PNAS, 104: 7552-7557.
Julie Sprunt, Summer 2005
Randall Graham 2004-2005
Graham, R.B., Nolasco, M., Peterlin, B. and Garcia, C.K. (2005) Nonsense Mutations in Folliculin Presenting as Isolated Spontaneous Pneumothorax in Adults. Am. J. Resp. Crit. Care Med., 172:39-44.
Bala Sambandam, Summer 2004