Postdoctoral training, University of California at San Francisco, cancer biology
PhD in biochemistry, Dartmouth Medical School, Hanover, NH
BS in biochemistry, Fudan University, Shanghai, China
- Stem Cell Biology
Telomerase expression and telomere maintenance are required for limitless proliferation of immortal cells, including pluripotent stem cells and the majority of cancer cells. Human telomerase is silenced during cell differentiation and consequently, somatic cells undergo finite numbers of cell division before senescing, due to their limited telomere reservoirs. On the other hand, telomerase is activated during the progression of many types of human cancers. Our current research projects are focused on studying the chromatin/epigenetic mechanisms of telomerase gene regulation using models of human somatic cells, pluripotent stem cells (PSCs, e.g. ESCs), induced pluripotent stem cells (iPSCs), and transgenic mice. Our goal is to dissect the critical steps and genetic elements involved in hTERT repression during cell differentiation and its activation during tumorigenesis and nuclear reprogramming. These mechanisms are also likely to contribute to human aging.
Because telomerase activity is required for proliferation and survival of cancer cells, telomerase inhibition is an important therapeutic anti-cancer strategy. Therefore, we will also identify small molecules that regulate telomerase activity in human cells.
Zhu’s research is supported by National Institute of General Medical Sciences, a National Institutes of Health Agency.
Zhang, F., Wang, S., and J. Zhu. ETV5 and c-Myc cooperate to de-repress human telomerase gene promoter via composite Ets/E-box motifs. (Accepted for publication by J. Biol. Chem., June, 2020)
Zhang, F., Cheng, D., Wang, S., and J. Zhu. Crispr/Cas9-mediated cleavages facilitate homologous recombination during genetic engineering of a large chromosomal region. (Accepted for publication by Biotechnology and Bioengineering, May, 2020)
Cheng, D., Zhao, Y., Zhang, F., Zhang, J., Wang, S., and J. Zhu. (2019) Engineering a humanized telomerase reverse transcriptase gene in mouse embryonic stem cells. Scientific Reports 9(1):9683 (DOI:10.1038/s41598-019-46160-5) [PMCID: PMC6609615]
Yu, Y., Jia, W., Lyu, Y., Su, D., Bai, M., Shen, J., Qiao, J., Han, T., Liu, W., Chen, J., Chen, W., Ye, D., Guo, X., Zhu, S., Xi, J., Zhu, R., Wan, X., Gao, S., Zhu, J.*, and Kang, J.* (2019) Pwp1 regulates telomere length by stabilizing shelterin complex and maintaining histone H4K20 trimethylation. Cell Discovery 5, 47. (DOI:10.1038/s41421-019-0116-8) [PMCID:PMC6868014]
Cheng, D., Wang, S., Jia, W., Zhao, Y., Zhang, F., Kang, J., and J. Zhu. (2017) Regulation of human and mouse telomerase genes by genomic contexts and transcription factors during embryonic stem cell differentiation. Scientific Reports 7(1):16444 (DOI:10.1038/s41598-017-16764-w) [PMCID: PMC5703907]
Cheng, D., Zhao, Y., Wang, S., Zhang, F., Russo, M., McMahon, S.B., and J. Zhu. (2016) Repression of telomerase gene promoter requires human-specific genomic context and is mediated by multiple HDAC1-containing corepressor complexes. The FASEB Journal. 31(3):1165-1178. (DOI:10.1096/fj.201601111R) [PMCID:PMC5295725]
Cheng, D., Zhao, Y., Wang, S., Jia, W., Kang, J., and Zhu, J. (2015) Human Telomerase Reverse Transcriptase (hTERT) Transcription Requires Sp1/Sp3 Binding to the Promoter and a Permissive Chromatin Environment. J. Biol. Chem. 290(50):30193-203. [PMCID: PMC4706010]
Ma, Y., Wang, S., Zhao, Y., Hao, S., Spector, DJ., Lim, B., Zheng, S., El-Deiry, WS., and Zhu, J. (2015) A combinatory strategy for circulating tumor cell detection using microfilter capturing and adenoviral imaging. Mocular Cancer Therapeutics, 14(3):835-43. [PMCID: PMC4456279]
Zhao, Y., Cheng, D., Wang, S., and Zhu, J. (2014) Dual roles of c-Myc in the regulation of hTERT gene. Nucleic Acids Research, 42(16):10385-98.
Jia W, Wang S, Horner JW, Wang N, Wang H, Gunther EJ, DePinho RA, Zhu, J. (2011) A BAC transgenic reporter recapitulates in vivo regulation of human telomerase reverse transcriptase in development and tumorigenesis. The FASEB Journal. 25: 979-89.
Wang S, Hu C, Zhao Y, Zhu J. (2010) Distinct and Temporal Roles of Nucleosomal Remodeling and Histone Deacetylation in the Repression of hTERT Gene. Molecular Biology of the Cell. Vol. 21: 821–832.
Mathew R, Jia W, Sharma A, Zhao Y, Clarke LE, Cheng X, Wang H, Salli U, Vrana KE, Robertson GP, Zhu J, Wang S. (2010) Robust activation of the human but not mouse telomerase gene during the induction of pluripotency. The FASEB Journal. 24:2702-2715.
Zhao Y, Wang S, Popova EV, Grigoryev SA, Zhu J. (2009) Rearrangement of Upstream Sequences of the hTERT Gene during Cellular Immortalization. Gene, Chromosomes and Cancer. 48:963-974.
Wang S, Zhao Y, Leiby MA, Zhu J. (2009) Studying human telomerase gene transcription by a chromatinized reporter generated by recombinase-mediated targeting of a bacterial artificial chromosome. Nucleic Acids Research. 37: e111.
Wang S, Zhao Y, Hu C, Zhu J. (2009) Differential repression of human and mouse TERT genes during cell differentiation. Nucleic Acid Research. 37:2618-29.
Honors and Awards
2000-02 & 2012-13: Cancer Research Awards, W.W. Smith Charitable Trust
2004-09: American Cancer Society Research Scholar
2001-03: New Independent Investigator Award, Four Diamonds Fund
1993-96: Special Fellow, Leukemia Society of America
1985: CUSBEA Exchange student (China and United States Biochemistry and Molecular Biology Examination Application)