Medical Student Research Fellowship for Summer 2010

Mentor: Christine Kim Garcia, MD/PhD
Department: McDermott/Internal Medicine
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:

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 analyzing the data collected after detailed phenotypic characterization of 20 subjects with inherited mutations in telomerase and 20 family member controls. We will determine if telomere lengths of circulating leukocytes are associated with clinical or preclinical 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:

Alberto Diaz de Leon, Doris Duke student 2009-2010, after 4th year of medical school:
Diaz de Leon, A., Cronkhite, J. T., Katzenstein, A.-L., Godwin, J. D., Raghu, G., Glazer C. S., Rosenblatt, R. L., Girod, C. E., Garrity, E. R., Xing, C. and Garcia, C. K. Telomere Lengths, Pulmonary Fibrosis and Telomerase (TERT) Mutations. PLoS One, submitted.

Ji (Erica) Han, MS1, Summer 2009

Arhaanth Reddy, MSI, Summer 2008

Randall Graham, MSI, Summer 2007

Phillip Kuan, Doris Duke student 2005-2006, between 2nd and 3rd year of medical school:
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.

Wang, Y., Kuan, P. J., Chao, X., Cronkhite, J. T., Torres, F., Rosenblatt, R. L., DiMaio, J. M., Kinch, L. N., Grishin, N. V. and Garcia, C. K. (2009) Genetic Defects in Surfactant Protein A2 Associated with Pulmonary Fibrosis and Lung Cancer. American Journal of Human Genetics, 84(1): 52-59.

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, MSI, Summer 2004