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.
"Identification of purple sea urchin telomerase RNA using a next-generation sequencing based approach. ," Y. Li, J.D. Podlevsky, M. Marz, X. Qi, S. Hoffmann, P.F. Stadler and J.J.-L. Chen, RNA 19 852-860 (2013)
"A homozygous telomerase T motif variant resulting in markedly reduced repeat addition processivity in siblings with Hoyeraal Hreidarsson syndrome.," M.M. Gramatges, X. Qi, G.S. Sasa, J.J.-L. Chen and A.A. Bertuch, Blood 121 3586-3593 (2013)
"RNA/DNA hybrid affinity determines telomerase template-translocation efficiency," X. Qi, M. Xie, A.F. Brown, C.J. Bley, J.D. Podlevsky and J.J.-L. Chen , EMBO J. 31 150-161 (2012)
"The common ancestral core of vertebrate and fungal telomerase RNAs.," X. Qi, Y. Li, S. Honda, S. Hoffmann, M. Marz. A. Mosig, J.D. Podlevsky, P.F. Stadler, E. Selker and J.J.-L. Chen, Nucleic Acids Research 41 450-462 (2012)
"It all comes together at the ends: Structure, function, and biogenesis of telomerase," J.D. Podlevsky and J.J.-L. Chen , Mutation Research 730 3-11 (2012)