李剛教授

1. Cancer Epigenetics
Numerous epigenetic regulators have been found to be mutated in a wide variety of tumors. However, in many cases whether those mutations are “driver” mutations or merely “passenger” mutations remains to be proven, and their mechanisms of action remain to be elucidated. We are taking a multidisciplinary approach, combining conventional biochemistry, mouse genetics, genome-wide approach and bioinformatics to investigate these questions. Another research interest is to build cell-based high throughput screening systems to screen epigenetic drugs for cancer therapy.

2. Signal transduction pathways in Epigenetics
An understanding of how different epigenetic statuses are established in different cell types and orchestrated by cell signaling is still very limited. To address these questions, my laboratory will initially focus on studying the posttranslational modification of epigenetic regulators and how PcG proteins are recruited to their targets.

1. Guan X, Deng H, Choi UL, Li Z, Yang Y, Zeng J, Liu Y, Zhang X, Li G. EZH2 overexpression dampens tumor-suppressive signals via an EGR1 silencer to drive breast tumorigenesis. Oncogene. 2020 Oct 2. doi:10.1038/s41388-020-01484-9.
2. Zhao Z, Zhang Z, Li J, Dong Q, Xiong J, Li Y, Lan M, Li G, Zhu B. Sustained TNF-α stimulation induces transcriptional memory that greatly enhances signal sensitivity and robustness. Elife. 2020 Nov 6;9:e61965. doi: 10.7554/eLife.61965.
3. Yang Y, Li G. Post-translational modifications of PRC2: signals directing its activity. Epigenetics Chromatin. 2020 Oct 31;13(1):47. doi: 10.1186/s13072-020-00369-1.
4. Zhang T, Guan X, Choi UL, Dong Q, Lam MMT, Zeng J, Xiong J, Wang X, Poon TCW, Zhang H, Zhang X, Wang H, Xie R, Zhu B, Li G. Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation. Epigenetics Chromatin. 2019 Jun 4;12(1):32. doi: 10.1186/s13072-019-0281-x.
5. Cui M, Ying R, Jiang X, Li G, Zhang X, Zheng J, Yip Tam K, Liang B, Shi A, Gobel V, Zhang H. A model of hereditary sensory and autonomic neuropathy type 1 reveals a role of glycosphingolipids in neuronal polarity. J Neurosci. 2019 May 28. pii: 2541-18. doi: 10.1523/JNEUROSCI.2541-18.2019. [Epub ahead of print]
6. Zhao Z, Lan M, Li J, Dong Q, Li X, Liu B, Li G, Wang H, Zhang Z, Zhu B. The proinflammatory cytokine TNFα induces DNA demethylation-dependent and -independent activation of interleukin-32 expression. J Biol Chem. 2019 Apr 26;294(17):6785-6795. doi: 10.1074/jbc.RA118.006255. Epub 2019 Mar 1.
7. Deng H, Guan X, Gong L, Zeng J, Zhang H, Chen MY, Li G. CBX6 is negatively regulated by EZH2 and plays a potential tumor suppressor role in breast cancer. Sci Rep. 2019 Jan 17;9(1):197. doi: 10.1038/s41598-018-36560-4.
8. Wang C, Cheng X, Tan J, Ding Z, Wang W, Yuan D, Li G, Zhang H, Zhang X. Reductive cleavage of C[double bond, length as m-dash]C bonds as a new strategy for turn-on dual fluorescence in effective sensing of H2S. Chem Sci. 2018 Sep 11;9(44):8369-8374. doi: 10.1039/c8sc03430c. eCollection 2018 Nov 28.
9. Wu X, Li G, Xie R. Decoding the role of TET family dioxygenases in lineage specification. Epigenetics Chromatin. 2018 Oct 5;11(1):58. doi: 10.1186/s13072-018-0228-7. Review.
10. Zeng J, Li G. TFmapper: A tool for searching putative factors regulating gene expression using ChIP-seq data.  Int J Biol Sci. 2018 doi:10.7150/ijbs.28850.
11. Cheng X, Zheng J, Li G, Göbel V, Zhang H. Degradation for better survival? Role of ubiquitination in epithelial morphogenesis. Biological Reviews. 2018; 93 (3):1438-1460.
12. Deng H, Zeng J, Zhang T, Gong L, Zhang H, Cheung E, Jones C, Li G. Histone H3. 3K27M Mobilizes Multiple Cancer/Testis (CT) Antigens in Pediatric Glioma Molecular Cancer Research 2018; 16 (4):623-633.
13. Zou Z, Yin Y, Lin J, Hsu LJ, Brandon VL, Yang F, Jove R, Jandial R, Li G, and Chen MY Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3. Journal of neurosurgery. 2016; 124 (5):1310-1318
14. Li G, Warden C, Zou Z, Neman J, Krueger JS, Jain A, Jandial R, Chen M. Altered Expression of Polycomb Group Genes in Glioblastoma Multiforme. PLoS One. 2013 Nov 15;8(11):e80970.
15. Zou Z, Denny E, Brown CE, Jensen MC, Li G, Fujii T, Neman J, Jandial R, Chen M. Cytotoxic T lymphocyte trafficking and survival in an augmented fibrin matrix carrier. PLoS One. 2012; 7(4):e34652.
16. Beck DB, Bonasio R, Kaneko S, Li G, Li G, Margueron R, Oda H, Sarma K, Sims RJ 3rd, Son J, Trojer P, Reinberg D. Chromatin in the Nuclear Landscape. Cold Spring Harb Symp Quant Biol. 2010;75:11-22.
17. Li G, Margueron R, Ku M, Chambon P, Bernstein B, Reinberg D. Jarid2 and PRC2, partners in regulating gene expression. Genes & Development. 2010 Feb 15;24 (4):368-80.
18. Kaneko S, Li G*, Son J, Xu CF, Margueron R, Neubert TA, Reinberg D. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes & Development. 2010 Dec 1;24(23):2615-20. *Co-first author.
19. Huo YY, Li G*, Duan RF, Gou Q, Fu CL, Hu YC, Song BQ, Yang ZH, Wu DC, Zhou PK. PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts. Free Radic Biol Med. 2008 Apr 15;44(8):1578-91. *Co-first author.
20. Huo YY, Hu YC, He XR, Wang Y, Song BQ, Zhou PK, Zhu MX, Li G*, Wu DC. Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells. Cell Biol Toxicol. 2007 Mar; 23(2): 113-28. *Corresponding author.
21. Freeman D, Lesche R, Kertesz N, Wang S, Li G, Gao J, Groszer M, Martinez-Diaz H, Rozengurt N, Thomas G, Liu X, Wu H. Genetic background controls tumor development in pten-deficient mice. Cancer Res. 2006 Jul 1;66(13):6492-6.
22. Li G*, Hu Y, Huo Y, Liu M, Freeman D, Gao J, Liu X, Wu DC, Wu H. PTEN deletion leads to up-regulation of a secreted growth factor pleiotrophin. J Biol Chem. 2006;281(16):10663-8.  *Corresponding author.
23. Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J, Thomas GV, Li G, Roy-Burman P, Nelson PS, Liu X, Wu H. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 2003 Sep; 4(3):209-21.
24. Li G, Robinson GW, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N, Wagner K, Wu DC, Lane TF, Liu X, Henninghausen LH. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 2002 Sep;129(17):4159-70.