Research and Teaching InterestsWe are interested in understanding the structure, function and evolution of ribonucleoprotein (RNP) complexes in cells. Our attention currently focuses on the telomerase RNP enzyme, a unique reverse transcriptase essential for maintaining telomere length in most eukaryotes. Telomeres act as caps at the ends of chromosomes, and are required for chromosome stability. Telomerase elongates telomere length by adding telomeric repeats to chromosome ends to counterbalance the natural shortening that occurs during DNA replication. Because of its role in chromosome stability, telomerase regulation is a critical step in tumorigenesis and aging. To maintain chromosome stability and infinite growth, telomerase is activated in immortal cells such as stem cells, germ line as well as 90% of human tumors. Moreover, patients with dyskeratosis congenita, a disease of premature aging, carry a mutation in the telomerase RNA (TR) or the telomerase reverse transcriptase protein (TERT) genes Elucidation of the molecular mechanism of telomerase function is the main goal of our lab and will have significant medical implications in cancer and aging. Our goals are to understand (1) how telomerase RNP is assembled and regulated in cells, (2) how different components of the complex participate in the regulation of telomerase function, and (3) how this RNP complex evolved in different eukaryotes. Our research employes a variety of approaches involving biochemical and biophysical techniques, as well as molecular genetics and molecular biology. |
Publications
"A novel motif in telomerase reverse transcriptase regulates telomere repeat addition rate and processivity," M. Xie, J.D. Podlevsky, X. Qi, C.J. Bley and J.J.L. Chen , Nucleic Acids Research in press (2009)
"Evolution of vault RNAs," P.F. Stadler, J.J.L. Chen, J. Hackermuller, S. Hoffmann, P. Khaitovich, A. Kretzschmar, A. Mosig, S.J. Prohaska, X. Qi, K. Schutt and K. Ullmann , Molecular Biology and Evolution 26 1975-1991 (2009)
"The Telomerase Database," J.D. Podlevsky, C.J. Bley, R.V. Omana, X. Qi and J.J.-L. Chen, Nucleic Acids Research, 36 D339-D343 (2008)
"Short telomeres are a risk factor for idiopathic pulmonary fibrosis," J.K. Alder, J.J.L. Chen, L. Lancaster, S. Danoff, S.C. Su, M. Prince, I. Vulto, M. Xie, X. Qi, R.M. Tuder, J.A. Phillips, P.M. Lansdorp, J.E. Loyd, M.Y. Armanios , Proc. Natl. Acad. Sci. U.S.A. 105 13051-13056 (2008)
"Structure and function of the smallest vertebrate telomerase RNA from teleost fish," M. Xie, A. Mosig, X. Qi, Y. Li, P.F. Stadler and J.J.L. Chen, Journal of Biological Chemistry, 283 2049-2059 (2008)
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