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Li Shang

Associate Professor


Contact: 66011259

The continued proliferation of human cells depends on the proper maintenance of the genomic information encoded in the 46 linear human chromosomes. The stability of these linear chromosomes depends on telomeres, which are maintained by telomerase.
Up-regulation of telomerase is found in more than 85% of human cancers, while telomerase insufficiency can cause early onset of human aging, highlighting the crucial role of telomerase regulation in both cancer therapy and human aging. On the one hand, we would like to inhibit overexpressed telomerase in tumor cells; on the other hand, we need to maintain the telomerase activity of normal stem cells to prevent early onset of aging.
My research goal is to elucidate mechanisms underlying the regulation of telomerase activity in cancer cells and normal stem cells, and to develop novel approaches for therapeutic intervention of human cancer and early onset of aging. Using both yeast and mammalian systems, I will focus on both (1) the regulation of telomerase activity by post-translational modification of telomerase and telomerase-related factors, and (2) the transcriptional regulation of human telomerase reverse transcriptase.

Tham C.Y., Poon L.F.,…Osato M. and Li S. High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform. Nat. Comm. 2023 Jan 17 14(1):281. doi: 10.1038/s41467-023-35823-7 

Nargund A.M.,… Li S.* and Tan P.* (Co-corresponding author) Chromatin Alterations Driven by MSH2 Deficiency Confer Cell Adhesion Deregulation and Sensitivity to BET Inhibition. 2022 Cancer Research 82(14):2538-2551 doi: 10.1158/0008-5472.CAN-21-2072 

Fan X,…Li S, …Low A. CXCL5 administration dampens inflammation and improves survival in murine lupus via myeloid and neutrophil pathways. Arthritis & Rheumatology 2022 Oct 14 doi:10.1002/art.42383 

Cai Y., …Li S, ... and Fullwood M.J. H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interaction. 2021 Nature Communications 12:1 doi: 10.1038/s41467-021-20940-y. 

Choo, XY,… Li S,... and Rackham O.J.L. Evaluating capture sequence performance for single-cell CRISPR activation experiments. ACS Synthetic Biology 2021 10(3), 640-645. doi:10.1021/acssynbio.0c00499. 

Xing M…Li S, Teh BT, and Tan P Genomic and epigenomic EBF1 alterations modulate Tert expression in gastric cancer. Journal of Clinical Investigation 2020 130(6):3005-3020 doi:10.1172/JCI126726. 

Yi Wei, B., Yeh ChingLin, Yeow Tee Goh, Li S., Liam Pock Ho, Tumor infiltrating lymphocytes from acute myeloid leukemia marrow can be reverted to CD45RA+ central memory state by reactivation in SIP (Simulated Infective Protocol). Immunobiology 224 (4), 526-531. (2020)

Xu, C.;  Ooi, W. F.;  Qamra, A.;  Tan, J.;  Chua, B. Y.-J.;  Ho, S. W. T.;  Das, K.;  Adam Isa, Z. F.;  Li, Z.;  Yao, X.;  Yan, T.;  Xing, M.;  Huang, K. K.;  Lin, J. S.;  Nandi, T.;  Tay, S. T.;  Lee, M. H.;  Tan, A. L. K.;  Ong, X.;  Ashktorab, H.;  Smoot, D.;  Li S.;  Ng, S.-C.;  Teh, B. T.; Tan, P., HNF4α pathway mapping identifies wild-type IDH1 as a targetable metabolic node in gastric cancer. Gut 69 (2), 231-242. (2020)

Ooi, W. F.;  Nargund, A. M.;  Lim, K. J.;  Zhang, S.;  Xing, M.;  Mandoli, A.;  Lim, J. Q.;  Ho, S. W. T.;  Guo, Y.;  Yao, X.;  Lin, S. J.;  Nandi, T.;  Xu, C.;  Ong, X.;  Lee, M.;  Tan, A. L.-K.;  Lam, Y. N.;  Teo, J. X.;  Kaneda, A.;  White, K. P.;  Lim, W. K.;  Rozen, S. G.;  Teh, B. T.;  Li, S.;  Skanderup, A. J.; Tan, P., Integrated paired-end enhancer profiling and whole-genome sequencing reveals recurrent CCNE1 and IGF2 enhancer hijacking in primary gastric adenocarcinoma. Gut, gutjnl-2018-317612. (2019)

Cai, Y.;  Zhang, Y.;  Loh, Y. P.;  Tng, J. Q.;  Lim, M. C.;  Cao, Z.;  Raju, A.;  Li S.;  Manikandan, L.;  Tergaonkar, V.;  Tucker-Kellogg, G.; Fullwood, M. J., H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions. bioRxiv, 684712. (2019)

TingDong, Y.;  Wen Fong, O.;  Qamra, A.;  Cheung, A.;  Ma, D.;  Gopinath Meenakshi, S.;  Chang, X.;  Xing, M.;  Poon, L.;  Wang, J.;  Loh, Y. P.;  Jess Hui Jie, H.;  Joscelyn Jun Quan, N.;  Muhammad Khairul, R.;  Aswad, L.;  Rozen, S. G.;  Ghosh, S.;  Bard, F. A.;  Sampath, P.;  Tergaonkar, V.;  Davies, J. O. J.;  Hughes, J. R.;  Goh, E.;  Bi, X.;  Fullwood, M. J.;  Tan, P.; Li S., HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nature Communications 9, 1. (2018)

Fan, X.;  Guo, D.;  Cheung, A. M. S.;  Poon, Z. Y.;  Yap, C. S.;  Goh, S. E.;  Guo, D.;  Li, H.;  Bari, S.;  Li S.;  Lim, K. H.; Hwang, W. Y. K., Mesenchymal Stromal Cell (MSC)-Derived Combination of CXCL5 and Anti-CCL24 Is Synergistic and Superior to MSC and Cyclosporine for the Treatment of Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation 24 (10), 1971-1980. (2018)

Bari, S.;  Zhong, Q.;  Fan, X.;  Poon, Z.;  Lim, A. S. T.;  Lim, T. H.;  Dighe, N.;  Li S.;  Chiu, G. N. C.;  Chai, C. L. L.; Hwang, W. Y. K., 199 - Ex Vivo Expansion of SCID-Repopulating CD34+CD90+CD49f+Hematopoietic Stem & Progenitor Cells From Non-Enriched Human Umbilical Cord Blood with Novel Azole-Based Small Molecules. Biology of Blood and Marrow Transplantation 24 (3, Supplement), S189. (2018)

Bari, S.;  Zhong, Q.;  Fan, X.;  Poon, Z.;  Lim, A. S. T.;  Lim, T. H.;  Dighe, N.;  Li S.;  Chiu, G. N. C.;  Chai, C. L. L.; Hwang, W. Y. K., Ex Vivo Expansion of CD34+CD90+CD49f+ Hematopoietic Stem and Progenitor Cells from Non-Enriched Umbilical Cord Blood with Azole Compounds. STEM CELLS Translational Medicine 7 (5), 376-393. (2018)

Yao, X.;  Tan, J.;  Lim, K. J.;  Koh, J.;  Ooi, W. F.;  Li, Z.;  Huang, D.;  Xing, M.;  Chan, Y. S.;  Qu, J. Z.;  Tay, S. T.;  Wijaya, G.;  Lam, Y. N.;  Hong, J. H.;  Lee-Lim, A. P.;  Guan, P.;  Ng, M. S. W.;  He, C. Z.;  Lin, J. S.;  Nandi, T.;  Qamra, A.;  Xu, C.;  Myint, S. S.;  Davies, J. O. J.;  Goh, J. Y.;  Loh, G.;  Tan, B. C.;  Rozen, S. G.;  Yu, Q.;  Tan, I. B. H.;  Cheng, C. W. S.;  Li S.;  Chang, K. T. E.;  Tan, P. H.;  Silver, D. L.;  Lezhava, A.;  Steger, G.;  Hughes, J. R.;  Teh, B. T.; Tan, P., VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma. Cancer Discovery 7 (11), 1284. (2017)

Ramlee, M. K.;  Wang, J.;  Cheung, A. M. S.; Li S., Using a Fluorescent PCR-capillary Gel Electrophoresis Technique to Genotype CRISPR/Cas9-mediated Knockout Mutants in a High-throughput Format. J Vis Exp (122), 55586. (2017)

Gopalakrishnan, V.; Tan, C. R.; Li S., Sequential phosphorylation of CST subunits by different cyclin-Cdk1 complexes orchestrate telomere replication. Cell Cycle 16 (13), 1271-128. (2017)

Arya, D.;  Sachithanandan, S. P.;  Ross, C.;  Palakodeti, D.;  Li S.; Krishna, S., MiRNA182 regulates percentage of myeloid and erythroid cells in chronic myeloid leukemia. Cell death & disease 8 (1), e2547-e2547. (2017)

Ooi, W. F.;  Xing, M.;  Xu, C.;  Yao, X.;  Ramlee, M. K.;  Lim, M. C.;  Cao, F.;  Lim, K.;  Babu, D.;  Poon, L.-F.;  Lin Suling, J.;  Qamra, A.;  Irwanto, A.;  Qu Zhengzhong, J.;  Nandi, T.;  Lee-Lim, A. P.;  Chan, Y. S.;  Tay, S. T.;  Lee, M. H.;  Davies, J. O. J.;  Wong, W. K.;  Soo, K. C.;  Chan, W. H.;  Ong, H. S.;  Chow, P.;  Wong, C. Y.;  Rha, S. Y.;  Liu, J.;  Hillmer, A. M.;  Hughes, J. R.;  Rozen, S.;  Teh, B. T.;  Fullwood, M. J.;  Li S.; Tan, P., Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity. Nature Communications 7, 12983. (2016)

Liu, C. C.;  Ma, D. L.;  Yan, T.-D.;  Fan, X.;  Poon, Z.;  Poon, L.-F.;  Goh, S.-A.;  Rozen, S. G.;  Hwang, W. Y. K.;  Tergaonkar, V.;  Tan, P.;  Ghosh, S.;  Virshup, D. M.;  Goh, E. L. K.; Li S., Distinct Responses of Stem Cells to Telomere Uncapping—A Potential Strategy to Improve the Safety of Cell Therapy. STEM CELLS 34 (10), 2471-2484. (2016)

Khattar, E.;  Kumar, P.;  Liu, C. Y.;  Akıncılar, S. C.;  Raju, A.;  Lakshmanan, M.;  Maury, J. J. P.;  Qiang, Y.;  Li S.;  Tan, E. Y.;  Hui, K. M.;  Shi, M.;  Loh, Y. H.; Tergaonkar, V., Telomerase reverse transcriptase promotes cancer cell proliferation by augmenting tRNA expression. J Clin Invest 126 (10), 4045-4060. (2016)

Ramlee, M. K.;  Yan, T.;  Cheung, A. M. S.;  Chuah, C. T. H.; Li S., High-throughput genotyping of CRISPR/Cas9-mediated mutants using fluorescent PCR-capillary gel electrophoresis. Scientific Reports 5, 15587. (2015)

Koh, C. M.;  Khattar, E.;  Leow, S. C.;  Liu, C. Y.;  Muller, J.;  Ang, W. X.;  Li, Y.;  Franzoso, G.;  Li S.;  Guccione, E.; Tergaonkar, V., Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity. J Clin Invest, 125 (5), 2109-2122. (2015)

Akıncılar, S. C.;  Low, K. C.;  Liu, C. Y.;  Yan, T. D.;  Oji, A.;  Ikawa, M.;  Li S.; Tergaonkar, V., Quantitative assessment of telomerase components in cancer cell lines. FEBS Letters 589 (9), 974-984. (2015)

Liu, C.-C.;  Gopalakrishnan, V.;  Poon, L.-F.;  Yan, T.; Li S., Cdk1 regulates the temporal recruitment of telomerase and Cdc13-Stn1-Ten1 complex for telomere replication. Molecular and cellular biology 34 (1), 57-70. (2014)

Xu, L.;  Li S.; Stohr, B. A., The Role of Telomere Biology in Cancer. Annual Review of Pathology: Mechanisms of Disease 8 (1), 49-78. (2013)

Ho, L. P.;  Yit, P. S.;  Ng, L. H.;  Linn, Y. C.;  Zhao, Y.;  Sun, L.;  Ling, K. L.;  Chai Koh, M. B.;  Monica Shih, M.-C.;  Li S.;  Wang, X. Y.;  Tien, S. L.; Goh, Y. T., The Road to Memory: An Early Rest for the Long Journey. The Journal of Immunology  191 (11), 5603. (2013)

Bari, S.;  Chu, P. P. Y.;  Lim, A.;  Fan, X.;  Gay, F. P. H.;  Bunte, R. M.;  Lim, T. K. H.;  Li S.;  Chiu, G. N. C.; Hwang, W. Y. K., Protective role of functionalized single walled carbon nanotubes enhance ex vivo expansion of hematopoietic stem and progenitor cells in human umbilical cord blood. Nanomedicine: Nanotechnology, Biology and Medicine 9 (8), 1304-1316. (2013)

Ghosh, A.;  Saginc, G.;  Leow, S. C.;  Khattar, E.;  Shin, E. M.;  Yan, T. D.;  Wong, M.;  Zhang, Z.;  Li, G.;  Sung, W.-K.;  Zhou, J.;  Chng, W. J.;  Li S.;  Liu, E.; Tergaonkar, V., Telomerase directly regulates NF-κB-dependent transcription. Nature Cell Biology 14 (12), 1270-1281. (2012)

Li S.., Cell-cycle-dependent telomere elongation by telomerase in budding yeast. Bioscience Reports 2011, 31 (3), 169-177. (2011)

Li S.;  Makovets, S.;  Matsuguchi, T.;  Blethrow, J. D.;  Shokat, K. M.; Blackburn, E. H., Cdk1-Dependent Phosphorylation of Cdc13 Coordinates Telomere Elongation during Cell-Cycle Progression. Cell, 136 (1), 50-61. (2009)

Li S.;  Nosrati, M.; Kashani-Sabet, M., Knockdown of Telomerase RNA Using Hammerhead Ribozymes and RNA Interference. In Telomerase Inhibition: Strategies and Protocols, Andrews, L. G.; Tollefsbol, T. O., Eds. Humana Press: Totowa, NJ, pp 113-131. (2007)

Bagheri, S.;  Nosrati, M.;  Li S.;  Fong, S.;  Torabian, S.;  Rangel, J.;  Moore, D. H.;  Federman, S.;  Laposa, R. R.;  Baehner, F. L.;  Sagebiel, R. W.;  Cleaver, J. E.;  Haqq, C.;  Debs, R. J.;  Blackburn, E. H.; Kashani-Sabet, M., Genes and pathways downstream of telomerase in melanoma metastasis. Proceedings of the National Academy of Sciences of the United States of America 103 (30), 11306-11311. (2006)

Li S.;  Crothers, J.;  Haqq, C. M.; Blackburn, E. H., Cellular and Gene Expression Responses Involved in the Rapid Growth Inhibition of Human Cancer Cells by RNA Interference-mediated Depletion of Telomerase RNA. Journal of Biological Chemistry 280 (25), 23709-23717. (2005)

Nosrati, M.;  Li S.;  Bagheri, S.;  Ginzinger, D.;  Blackburn, E. H.;  Debs, R. J.; Kashani-Sabet, M., Antitumor Activity of Systemically Delivered Ribozymes Targeting Murine Telomerase RNA. Clinical Cancer Research  10 (15), 4983. (2004)

Li S.;  Rosenberg, J. E.;  Donjacour, A. A.;  Botchkina, I. L.;  Hom, Y. K.;  Cunha, G. R.; Blackburn, E. H., Rapid Inhibition of Cancer Cell Growth Induced by Lentiviral Delivery and Expression of Mutant-Template Telomerase RNA and Anti-telomerase Short-Interfering RNA. Cancer Research 64 (14), 4833. (2004)

Zheng, L.;  Pan, H.;  Li S.;  Flesken-Nikitin, A.;  Chen, P.-L.;  Boyer, T. G.; Lee, W.-H., Sequence-Specific Transcriptional Corepressor Function for BRCA1 through a Novel Zinc Finger Protein, ZBRK1. Molecular Cell 6 (4), 757-768. (2000)

Li S.;  Ting, N. S. Y.;  Zheng, L.;  Chen, P.-L.;  Ziv, Y.;  Shiloh, Y.;  Lee, E. Y. H. P.; Lee, W.-H., Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 406 (6792), 210-215. (2000)