The goal of the research program in my laboratory is to identify the genes that predispose individuals to lung disease. To achieve these goals, we recruit and characterize families and individuals with pulmonary disease. We use DNA collected from individuals to map and identify the genetic underpinnings of their diseases. We currently have over 200 families participating in our studies. Identification of defective genes highlights the role of different pathways that can lead to disease. These discoveries may lead to future novel treatments and biomarkers.
Using our collection of families, we recently mapped a locus for familial pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a lethal, scarring disease of the lung that typically affects older adults. It can be seen in multiple individuals in the same family, with an autosomal dominant inheritance pattern with decreased penetrance and variable expression. We have identified mutations in the genes encoding telomerase in patients with this disease. This discovery has highlighted the role of telomerase dysfunction as an unanticipated pathway leading to pulmonary fibrosis.
My laboratory also studies other pulmonary diseases affecting adults that are poorly understood and for which few treatments exist, such as of familial spontaneous pneumothorax, a rare subtype of emphysema. This disease is characterized by the formation of multiple holes or blebs within the lung. We used genetic approaches to identify mutations in the gene encoding folliculin as a cause of this disease and have linked this disease with Birt-Hogg-Dubé syndrome, a disorder characterized by multiple skin papules, pneumothoraces, and kidney cancer.
RESEARCH INTERESTS
Genetic Basis of Adult Pulmonary Diseases
Idiopathic Pulmonary Fibrosis
Familial Spontaneous Pneumothorax
Human Genetics
Molecular Genetics
RECENT PUBLICATIONS
Cronkite, J. T., Xing, C., Raghu, G., Chin, K., Torres, F., Rosenblatt, R. L., and Garcia, C. K., "Telomere Shortening in Familial and Sporadic Pulmonary Fibrosis" Am. J. Resp. Crit. Care Med., Epub ahead of print July 2008
Garcia, C. K., Wright, W.E. and Shay, J.W., "Human Diseases of Telomerase Dysfunction: Insights into Tissue Aging" Nucleic Acid Research, 35:7406-7416, October 2007
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, "Adult-Onset Pulmonary Fibrosis Caused by Mutations in Telomerase" PNAS, 104:7552-7557, 2007
Graham, Randall B., Nolasco, Melissa, Peterlin, Borut and Garcia, Christine Kim, "Nonsense Mutations in Folliculin Presenting as Isolated Spontaneous Pneumothorax in Adults." American Journal of Respiratory and Critical Care Medicine, 172:39-44, 2005
Cohen, J., Pertsemlidis, A., Kotowski, I.K., Graham, R., Garcia, C.K., and Hobbs, H.H., "Low LDL cholesterol in African Americans resulting from frequent nonsense mutations in PCSK9." Nature Genetics, 37:161-165, 2005
SIGNIFICANT PUBLICATIONS
Christine Kim Garcia, Kenneth Wilund, Marcello Arca, Giovanni Zuliani, Renato Fellin, Mario Maioli, Sebastiano Calandra, Stefano Bertolini, Fausto Cossu, Nick Grishin, Robert Barnes, Jonathan C. Cohen, and Helen H. Hobbs, "Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein" Science, 292:1394-1398, May 2001
Christine Kim Garcia, Joseph L. Goldstein, Ravindra K. Pathak, Richard G. W. Anderson, and Michael S. Brown, "Molecular Characterization of a Membrane Transporter for Lactate, Pyruvate, and Other Monocarboxylates: Implications for the Cori Cycle" Cell, 76:865-873, March 1994
Point and right click (click and hold for Mac users) your mouse onand select "Save this link (or target) as..." option to save the file to your local computer.
and select "Save this link (or target) as..." option to save the file to your local computer.