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Dr. Chen's Research Group |
Research and Teaching Interests
We 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.
Representative Publications
"The Telomerase Database," J.D. Podlevsky, C.J. Bley, R.V. Omana, X. Qi and J.L. Chen, Nucleic Acids Research, 36, D339-D343 (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.L. Chen, Journal of Biological Chemistry, 283, 2049-2059 (2008).
"Telomerase mutations in families with idiopathic pulmonary fibrosis.," M. Armanios, J.L. Chen, W.E. Lawson, J.K. Alder, R.G. Ingersoll, C. Markin, M. Xie, J. Cogan, J.A. Philips III, P.M. Lansdorp, C.W. Greider and J.E. Loyd, New England Journal of Medicine 356, 1317-1326 (2007).
"Identification and characterization of sea squirt telomerase reverse transcriptase," Y. Li, J.A. Yates and J.L. Chen, Gene 400, 16-24 (2007).
"WABI2007: Homology search with fragmented nucleic acid sequence patterns. ," A. Mosig, J.L. Chen and P.F. Stadler, Lect. Notes Comput. Sc. 4645, 335-345 (2007).
"Structure and function of eukaryotic ribonuclease P RNA," S.M. Marquez, J.L. Chen, D. Evans and N.R. Pace, Molecular Cell 24, 445-456 (cover) (2006).
"Functional analysis of the pseudoknot structure in human telomerase RNA," J.L. Chen and C.W. Greider, Proc. Natl. Acad. Sci. U.S.A. 102, 8080-8085 (2005).
"Haploinsufficiency of hTERT leads to anticipation in autosomal dominant dyskeratosis congenital," M. Armanios, J.L. Chen, Y.-P. Chang, R.A. Brodsky, A. Hawkins, C.A. Griffin, J.R. Eshleman, A. Chakravarti, A. Hamosh and C.W. Greider , Proc. Natl. Acad. Sci. U.S.A. 102, 15960-15964 (2005).
"Telomerase biochemistry and biogenesis," J.L. Chen and C.W. Greider , Telomeres-2nd edition , 49-79 (2005).
"An emerging consensus for telomerase RNA structure," J.L. Chen and C.W. Greider, Proc. Natl. Acad. Sci. U.S.A. 101, 14683-14684 (2004).
"Telomerase RNA structure and function: implications for dyskeratosis congenita," J.L. Chen and C.W. Greider, Trends in Biochemical Sciences 29, 183-192 (2004).
"Template boundary definition in mammalian telomerase," J.L. Chen and C.W. Greider, Genes & Development 17, 2747-2752 (2003).
"Determinants in mammalian telomerase RNA that mediate enzyme processivity and cross-species incompatibility," J.L. Chen and C.W. Greider, EMBO J. 22, 304-314 (2003).
"A critical stem-loop structure in the CR4-CR5 domain of mammalian telomerase RNA," J.L. Chen, K.K. Opperman and C.W. Greider, Nucleic Acids Research 30, 592-597 (2002).
"Secondary structure of vertebrate telomerase RNA," J.L. Chen, M.A. Blasco and C.W. Greider, Cell 100, 503-514 (2000).
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