Medical Student Research Fellowship for Summer 2007

Mentor: Christine Kim Garcia, MD/PhD
Department: McDermott/IM
Room number: NA2.206
Mail Code: 8591
Phone number: 87424
E-mail: Christine.garcia@utsouthwestern.edu
Project title: The molecular basis of Familial Pulmonary Fibrosis

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)

patient-based
basic research

Brief Description of Project:

My laboratory has been focused upon discovering the molecular basis of inherited pulmonary disorders, including familial pulmonary fibrosis. We have collecting families with this disorder and have used a whole genome linkage strategy to map the disease to chromosome 5 in two large families. We sequenced a candidate gene within the linked region, TERT, which encodes telomerase and found mutations in the two families which co-segregated with the disease. Sequencing the probands of 44 additional unrelated families and 44 sporadic cases of interstitial lung disease revealed five other mutations in TERT. Heterozygous carriers of all the mutations in TERT had shorter telomeres than age-matched family members without the mutations.

Several mutation carriers have not reported any respiratory abnormalities, suggesting either incomplete penetrance or sub-clinical disease. In addition, many mutation carriers have reported osteoporosis and anemia, as well as pulmonary disease. We wish to study in detail the clinical manifestations displayed by the mutation carriers and their normal sibling controls. This will aid in the determining the full clinical spectrum of disease associated with heterozygous mutations in TERT.

Previous Research Activities or Publications with Medical Students:

Phillip Kuan, Doris Duke student

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, in press.

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