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Julian Chen

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Professor
Faculty, TEMPE Campus, Mailcode 1604
Professor
Faculty, TEMPE Campus, Mailcode 1604
Professor
Faculty, TEMPE Campus, Mailcode 1604
Biography

Dr. Julian J.-L. Chen is a Professor of Biochemistry at Arizona State University. His research interests are in structure and function of RNA molecules and ribonucleoprotein complexes. He received his Ph.D degree in molecular biology and biochemistry from Indiana University, Bloomington. He then worked as a postdoctoral fellow in Dr. Carol Greider's laboratory at Johns Hopkins University before he joined the faculty of Arizona State University in 2004. His research at ASU focuses on the structure, function and evolution of telomerase ribonucleoprotein complexes in cells. Telomerase is an enzyme essential for maintaining telomere length at chromosome ends in most eukaryotes. Because of its role in chromosome stability, telomerase regulation is a critical step in tumorigenesis and aging. Elucidation of the molecular mechanism of telomerase function will have significant impact on the development of therapeutics for human cancer and aging.

Education

Postdoctoral Fellow, Johns Hopkins University School of Medicine

Ph.D., Indiana University-Bloomington

Research 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.

Publications
  • Donaires, F.S., N.F. Scatena, R.M. Alves-Paiva, J.D. Podlevsky, B.A. Santana, A.C. Teixeira, J.J.-L. Chen, R.T. Calado and A.L.C. Martinelli (2017). Telomere biology and telomerase mutations in cirrhotic patients with hepatocellular carcinoma. PLoS ONE 12(8): e0183287. (PDF)
  • Podlevsky, J.D., Y. Li and J.J.-L. Chen (2016) The functional requirement of two structural domains within telomerase RNA emerged early in eukaryotes. Nucleic Acids Research 44(20): 9891-9901. (PDF
  • Podlevsky, J.D. and J.J.-L. Chen (2016) Evolutionary perspectives of telomerase RNA structure and function. RNA Biology 13(8): 720-730. (PDF)
  • Podlevsky, J.D., Y. Li and J.J.-L. Chen (2016) Structure and function of echinoderm telomerase RNA. RNA 22(2): 204-215.
  • Qi, X., D.R. Rand, J.D. Podlevsky, Y. Li, A. Mosig, P.F. Stadler and J.J.-L. Chen (2015) Prevalent and distinct spliceosomal 3'-end processing mechanisms for fungal telomerase RNA. Nature Communications 6, 6105.(PDF)
  • Stanley, S.E., J.J.-L. Chen, J.D. Podlevsky, J.K. Alder, N.N. Hansel, R. Mathias, X. Qi, N.N. Rafaels, R.A. Wise, E.K. Silverman, K.C. Barnes and M. Armanios (2015) Telomerase mutations in smokers with emphysema. The Journal of Clinical Investigation 125(2), 563-570.
  • J.J.-L. Chen and, J.D. Podlevsky (2015) Telomeres and telomerase. In Encyclopedia of Cell Biology, Vol. 1, R. Bradshaw and P. Stahl, eds. Waltham, MA: Academic Press, p. 418-425.  
  • Brown, A.F., J.D. Podlevsky, X. Qi, Y. Chen, M. Xie and J.J.-L. Chen (2014) A self-regulating template in human telomerase. Proc. Natl. Acad. Sci. U.S.A. 111(31): 11311-11316. (PDF)
  • Huang, J., A.F. Brown, J. Wu, J. Xue, C.J. Bley, D.P. Rand, L. Wu, R. Zhang, J.J.-L. Chen* and M. Lei* (2014) Structural basis for protein-RNA recognition in telomerase. Nature Structural and Molecular Biology 21: 507-512. (*co-corresponding)
  • Brown, A.F., J.D. Podlevsky and J.J.-L. Chen (2014) Telomerase: A eukaryotic DNA polymerase specialized in telomeric repeat synthesis. In Nucleic Acid Polymerases-1st edition, K. Murakami and M. Trakselis, eds., Springer Press. p.215-236.
  • Li, Y., J.D. Podlevsky, M. Marz, X. Qi, S. Hoffmann, P.F. Stadler and J.J.-L. Chen (2013) Identification of purple sea urchin telomerase RNA using a next-generation sequencing based approach. RNA 19: 852-860. (PDF)
  • Gramatges, M.M., X. Qi, G.S. Sasa, J.J.-L. Chen* and A.A. Bertuch* (2013) A homozygous telomerase T motif variant resulting in markedly reduced repeat addition processivity in siblings with Hoyeraal Hreidarsson syndrome. Blood 121(18): 3586-3593. (*contributed equally)
  • Podlevsky, J.D. and J.J.-L. Chen (2012) It all comes together at the ends: Structure, function, and biogenesis of telomerase. Mutation Research 730: 3-11. (Review)
  • Qi, X., Y. Li, S. Honda, S. Hoffmann, M. Marz. A. Mosig, J.D. Podlevsky, P.F. Stadler, E.U. Selker and J.J.-L. Chen (2012) The common ancestral core of vertebrate and fungal telomerase RNAs. Nucleic Acids Research 41: 450-462. (PDF)
  • Qi, X., M. Xie, A.F. Brown, C.J. Bley, J.D. Podlevsky and J.J.-L. Chen (2012) RNA/DNA hybrid binding affinity determines telomerase template translocation efficiency. EMBO J. 31: 150-161. (PDF)
  • Tzfati, Y. and J.J.-L. Chen (2012) Telomerase RNA: Structure, function, and molecular mechanisms. In Telomerases: Chemistry, Biology and Clinical Applications-1st edition, N.F. Lue and C. Autexier, eds., John Wiley & Sons, Inc. p.23-51.
  • Bley, C.J., X. Qi, D.P. Rand, C.R. Borges, R.W. Nelson and J.J.-L. Chen (2011) RNA-protein binding interface in the telomerase ribonucleoprotein. Proc. Natl. Acad. Sci. U.S.A. 108(51): 20333-20338. (PDF)
  • Parry, E.M., J.K. Alder, X. Qi, J.J.-L. Chen and M.Y. Armanios (2011) Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase. Blood 117 (21): 5607-5611.
  • Alder, J.K., J.D. Cogan, A.F. Brown, C.J. Anderson, W.E. Lawson, P.M. Lansdorp, J.A. Phillips 3rd, J.E. Loyd, J.J.-L. Chen, and M.Y. Armanios (2011) Ancestral mutation in telomerase causes defects in repeat addition processivity and manifests as familial pulmonary fibrosis. PLoS Genetics 7(3): e1001352.
  • Xie, M., J.D. Podlevsky, X. Qi, C.J. Bley and J.J.-L. Chen (2010) A novel motif in telomerase reverse transcriptase regulates telomere repeat addition rate and processivity. Nucleic Acids Research 38: 1982-1996.(PDF)
  • Stadler,P.F., J.J.-L. Chen, J. Hackermuller, S. Hoffmann, P. Khaitovich, A. Kretzschmar, A. Mosig, S.J. Prohaska, X. Qi, K. Schutt and K. Ullmann (2009) Evolution of vault RNAs. Molecular Biology and Evolution 26: 1975-1991.
  • Alder, J.K., 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 and M.Y. Armanios (2008) Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc. Natl. Acad. Sci. U.S.A. 105: 13051-13056.
  • Ye, Y., W. Wen, Y. Xiang, X. Qi, J.T. LaBelle, J.J.-L. Chen and J. Wang (2008) Direct electrochemical monitoring of RNase activity. Electroanalysis 20: 919-922.
  • Xie, M., A. Mosig, X. Qi, Y. Li, P.F. Stadler and J.J.-L. Chen (2008) Structure and function of the smallest vertebrate telomerase RNA from teleost fish. Journal of Biological Chemistry 283: 2049-2059. (PDF)
  • Podlevsky, J.D., C.J. Bley, R.V. Omana, X. Qi and J.J.-L. Chen (2008) The telomerase database. Nucleic Acids Research 36: D339-D343.
  • Li, Y., J.A. Yates and J.J.-L. Chen (2007) Identification and characterization of sea squirt telomerase reverse transcriptase. Gene 400: 16-24.
  • Xiang, Y, M. Xie, R. Bash, J.J.-L. Chen and J. Wang (2007) Ultrasensitive label-free aptamer-based electronic detection. Angewandte Chemie Int. Ed. 46(47): 9054-9056.
  • Mosig, A, J.J.-L. Chen and P.F. Stadler (2007) Homology search with fragmented nucleic acid sequence patterns. Lecture Notes in Computer Science. 4645: 335-345.
  • Armanios, M., J.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  (2007) Telomerase mutations in families with idiopathic pulmonary fibrosis. New England Journal of Medicine 356: 1317-1326.
  • Lin, C., M. Xie, J.J.-L Chen, Y. Liu and H. Yan (2006) Rolling-circle amplification of a DNA nanojunction. Angewandte Chemie Int. Ed. 45: 7537-7539.
  • Marquez, S.M., J.L Chen, D. Evans and N.R. Pace (2006) Structure and function of eukaryotic ribonuclease P RNA. Molecular Cell 24: 445-456.
  • Armanios, M., J.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 (2005) Haploinsufficiency of hTERT leads to anticipation in autosomal dominant dyskeratosis congenital. Proc. Natl. Acad. Sci. U.S.A. 102: 15960-15964.
  • Chen, J.-L. and C.W. Greider (2005) Telomerase biochemistry and biogenesis. In Telomeres-2nd edition, T. deLange, E. Blackburn and V. Lundblad, eds., Cold Spring Harbor Laboratory Press. p.49-79.
  • Chen, J.-L. and C.W. Greider (2005) Functional analysis of the pseudoknot structure in human telomerase RNA. Proc. Natl. Acad. Sci. U.S.A. 102: 8080-8085.
  • Chen, J.-L. and C.W. Greider (2004) An emerging consensus for telomerase RNA structure. Proc. Natl. Acad. Sci. U.S.A. 101: 14683-14684.
  • Chen, J.-L. and C.W. Greider (2004) Telomerase RNA structure and function: implications for dyskeratosis congenita. Trends in Biochemical Sciences 29: 183-192.
  • Chen, J.-L. and C.W. Greider (2003) Template boundary definition in mammalian telomerase. Genes & Development 17: 2747-2752.
  • Chen, J.-L. and C.W. Greider (2003) Determinants in mammalian telomerase RNA that mediate enzyme processivity and cross-species incompatibility. EMBO J. 22: 304-314.
  • Chen, J.-L., K.K. Opperman and C.W. Greider (2002) A critical stem-loop structure in the CR4-CR5 domain of mammalian telomerase RNA. Nucleic Acids Research 30: 592-597.
  • Chen, J.-L., M.A. Blasco and C.W. Greider (2000) Secondary structure of vertebrate telomerase RNA. Cell 100: 503-514.
  • Thomas, B.C., A.V. Kazantsev, J.-L. Chen and N.R. Pace (2000) Photoaffinity cross-linking and RNA structure analysis. Methods in Enzymology 318: 136-147.
  • Chen, J.-L., J.M. Nolan, M.E. Harris and N.R. Pace (1998) Comparative photocross-linking analysis of the tertiary structures of Escherichia coli and Bacillus subtilis RNase P RNAs. EMBO J. 17: 1515-1525.
  • Harris, M.E., A.V. Kazantsev, J.-L. Chen and N.R. Pace (1997) Analysis of the tertiary structure of the ribonuclease P ribozyme-substrate complex by site-specific photoaffinity crosslinking. RNA 3: 561-576.
  • Chen, J.-L. and N.R. Pace (1997) Identification of the universally conserved core of ribonuclease P RNA. RNA 3: 557-560.
Research Activity
  • Chen,Julian J-L*. Molecular Mechanism of Telomerase Action. HHS-NIH-NIGMS(8/1/2011 - 5/31/2020).
  • Chen,Julian J-L*. Biogenesis and Evolution of Fungal Telomerase RNA. NSF-BIO-MCB(8/1/2016 - 5/31/2019).
  • Chen,Julian J-L*, Chang,Yung. Development fo a fish model for dyskeratosis congenita and cancer research. HHS-NIH-NCRR(9/15/2008 - 6/30/2010).
  • Fromme,Petra*, Chen,Julian J-L. Structure and Function of the Proton-Turbine of the ATP-Synthase. HHS-NIH-NIBIB(9/1/2007 - 8/31/2013).
  • Chen,Julian J-L*. CAREER: Molecular Evolution of Telomerase Ribonucleoprotein: A Phylogenetic Study of Telomerase RNA Structure and Function. NSF-BIO(6/15/2007 - 5/31/2013).
Fall 2017
Course NumberCourse Title
BIO 495Undergraduate Research
Spring 2017
Course NumberCourse Title
BCH 461General Biochemistry
Fall 2016
Course NumberCourse Title
BIO 495Undergraduate Research
Spring 2016
Course NumberCourse Title
BCH 461General Biochemistry
Fall 2015
Course NumberCourse Title
BCH 461General Biochemistry
BIO 495Undergraduate Research
Spring 2015
Course NumberCourse Title
BCH 461General Biochemistry
BCH 465Protein & Nucleic Acid Biochem
Fall 2014
Course NumberCourse Title
BIO 495Undergraduate Research
Spring 2014
Course NumberCourse Title
BCH 461General Biochemistry
BCH 465Protein & Nucleic Acid Biochem
BIO 495Undergraduate Research
Fall 2013
Course NumberCourse Title
BCH 465Protein & Nucleic Acid Biochem
Spring 2013
Course NumberCourse Title
BCH 461General Biochemistry