韩霆博士

北京生命科学研究所高级研究员

Ting Han, Ph.D. Associate Investigator, NIBS, Beijing, China

Phone: 86-10-80726688

Fax: 86-10-80726689

E-mail:hanting@nibs.ac.cn

教育经历

Education

2006年 清华大学 生物学学士学位

B.S. Biology, Tsinghua University, Beijing, China

2013年 美国密西根大学细胞和发育生物学博士

Ph.D. Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA

工作经历

Professional Experience

2025 - 北京生命科学研究所高级研究员

Associate Investigator, National Institute of Biological Sciences, Beijing, China

2017 - 2024 北京生命科学研究所研究员

Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2013 - 2017 美国德克萨斯大学西南医学中心博士后

Postdoctoral Research Fellow, UT Southwestern Medical Center, Dallas, USA

研究概述

Research Description:

我们实验室的研究聚焦于化学生物学和癌症生物学两个互补领域，交汇点在于开发创新的癌症治疗策略。我们的目标是应对生物医学中的两大核心挑战：（1）缺乏通用方法来有效调控大多数致病蛋白；（2）可支持未来治疗创新的新靶点逐渐枯竭。在过去的几年中，我们通过“化学驱动”和“生物驱动”两种方法，在这些领域取得了进展。“化学驱动”的方法以基于表型的高通量筛选为起点，寻找具有选择性抗癌活性的小分子，并进一步解析其作用机制。“生物驱动”的方法通过体内CRISPR筛选，揭示肿瘤内在的免疫逃逸机制。这些研究不仅深化了我们对癌症生物学的认识，还提供了开发抗癌疗法的新靶点和化学起点。
The research in my lab is focused on two complementary areas at the forefront of chemical biology and cancer biology that converge at new therapeutic strategies for cancer treatment. We organize our efforts to tackle two challenges in biomedicine: (1) the lack of a general strategy to therapeutically modulate the majority of disease-causing proteins; (2) the exhaustion of new targets that can fuel future therapeutic innovations. Over the past several years, we have made considerable progress in these two areas by taking either a chemistry-first or a biology-first approach. The chemistry-first approach starts with phenotype-based high-throughput screening of small molecules with selective anticancer activities followed by the elucidation of their mechanisms of action. The biology-first approach employs in vivo CRISPR screening to identify tumor-intrinsic mechanisms of immune evasion. Such efforts not only improve our understanding of cancer biology but also provide novel targets and chemical starting points for developing anticancer therapy.

发表论文

Publications:

1. Lu, P., Cheng, Y., Xue, L., Ren, X., …, Huang, N.*, Han, T.* (2024). Selective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders. Cell, 2024 Dec 12;187(25):7126-7142.e20.  

2. Wang, L., Han, T.* (2024). Pharmacologic induction of ERα SUMOylation disrupt its chromatin binding. ACS Chemical Biology, 2024 Nov 15;19(11):2383-2392.  

3. Xu, X., Lu, Y., Cao, L., Miao, Y., Li, Y., Cui, Y., Han, T.* (2024). Tumor-intrinsic P2RY6 drives immunosuppression by enhancing PGE₂ production. Cell Rep, 43(7):114469. 

4. Cao, Z., Sun, W., Zhang, J., …, Han, T., Li, C. (2024). Total syntheses of (-)-macrocalyxoformins A and B and (-)-ludongnin C. Nature Communications, 15(1):6052.

5. Li, S., Han, T.* (2024). Frequent loss of FAM126A expression in colorectal cancer results in selective FAM126B dependency. iScience, 27(5):109646.

6. Cui, Y., Miao, Y., …, Xu, M.*, Han, T.* (2023). Activation of melanocortin-1 receptor signaling in melanoma cells impairs T cell infiltration to dampen antitumor immunity. Nature Communications, 14(1):5740. 

7.  Tao, Z., Cui, Y., Xu, X., Han, T.* (2022). FGFR redundancy limits the efficacy of FGFR4-selective inhibitors in hepatocellular carcinoma. Proc Natl Acad Sci U S A, 119(40):e2208844119

8. Yuan, H., Zhu, Y., Cheng, Y., Hou, J., Jin, F., Li, M., . . . Han, T.* (2022). BTK kinase activity is dispensable for the survival of diffuse large B-cell lymphoma. J Bio Chem, 298(11):102555

9. Lv, L., Chen, P., Cao, L., Li, Y., Zeng, Z., Cui, Y., . . . Han, T. * (2020). Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger Cyclin K degradation. Elife, 9. doi:10.7554/eLife.59994

10. Zeng, Z., & Han, T. * (2020). Discovering Nature's super glue. Nat Chem Biol. doi:10.1038/s41589-020-0586-x

11. Fuller, G. G., Han, T., Freeberg, M. A., Moresco, J. J., Ghanbari Niaki, A., Roach, N. P., . . . Kim, J. K. (2020). RNA promotes phase separation of glycolysis enzymes into yeast G bodies in hypoxia. Elife, 9. doi:10.7554/eLife.48480

12. Han, T., & Nijhawan, D. (2019). Exome Sequencing of Drug-Resistant Clones for Target Identification. Methods Mol Biol, 1888, 175-187. doi:10.1007/978-1-4939-8891-4_10

13. Zhang, J., Li, Z., Zhuo, J., Cui, Y., Han, T., & Li, C. (2019). Tandem Decarboxylative Cyclization/Alkenylation Strategy for Total Syntheses of (+)-Longirabdiol, (-)-Longirabdolactone, and (-)-Effusin. J Am Chem Soc, 141(20), 8372-8380. doi:10.1021/jacs.9b03978

14. Han, T., Goralski, M., Gaskill, N., Capota, E., Kim, J., Ting, T. C., . . . Nijhawan, D. (2017). Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science, 356(6336). doi:10.1126/science.aal3755

15. Han, T., Goralski, M., Capota, E., Padrick, S. B., Kim, J., Xie, Y., & Nijhawan, D. (2016). The antitumor toxin CD437 is a direct inhibitor of DNA polymerase alpha. Nat Chem Biol, 12(7), 511-515. doi:10.1038/nchembio.2082

16. Han, T., & Kim, J. K. (2016). Mapping the Transcriptome-Wide Landscape of RBP Binding Sites Using gPAR-CLIP-seq: Experimental Procedures. Methods Mol Biol, 1361, 77-90. doi:10.1007/978-1-4939-3079-1_5

17. Alessi, A. F., Khivansara, V., Han, T., Freeberg, M. A., Moresco, J. J., Tu, P. G., . . . Kim, J. K. (2015). Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1. Proc Natl Acad Sci U S A, 112(52), E7213-7222. doi:10.1073/pnas.1509499112

18. Han, T., & Kim, J. K. (2014). Driving glioblastoma growth by alternative polyadenylation. Cell Res, 24(9), 1023-1024. doi:10.1038/cr.2014.88

19. Wang, G., Han, T., Nijhawan, D., Theodoropoulos, P., Naidoo, J., Yadavalli, S., . . . McKnight, S. L. (2014). P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell, 158(6), 1324-1334.

20. Freeberg, M. A., Han, T., Moresco, J. J., Kong, A., Yang, Y. C., Lu, Z. J., . . . Kim, J. K. (2013). Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae. Genome Biol, 14(2), R13. doi:10.1186/gb-2013-14-2-r13

21. Billi, A. C., Alessi, A. F., Khivansara, V., Han, T., Freeberg, M., Mitani, S., & Kim, J. K. (2012). The Caenorhabditis elegans HEN1 ortholog, HENN-1, methylates and stabilizes select subclasses of germline small RNAs. PLoS Genet, 8(4), e1002617. doi:10.1371/journal.pgen.1002617

22. Gerstein, M. B., Lu, Z. J., Van Nostrand, E. L., Cheng, C., Arshinoff, B. I., Liu, T., . . . Waterston, R. H. (2010). Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science, 330(6012), 1775-1787. doi:10.1126/science.1196914

23. Mangone, M., Manoharan, A. P., Thierry-Mieg, D., Thierry-Mieg, J., Han, T., Mackowiak, S. D., . . . Kim, J. K. (2010). The landscape of C. elegans 3'UTRs. Science, 329(5990), 432-435. doi:10.1126/science.1191244

24. Han, T., Manoharan, A. P., Harkins, T. T., Bouffard, P., Fitzpatrick, C., Chu, D. S., . . . Kim, J. K. (2009). 26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans. Proc Natl Acad Sci U S A, 106(44), 18674-18679. doi:10.1073/pnas.0906378106

25. Friedlander, M. R., Adamidi, C., Han, T., Lebedeva, S., Isenbarger, T. A., Hirst, M., . . . Rajewsky, N. (2009). High-resolution profiling and discovery of planarian small RNAs. Proc Natl Acad Sci U S A, 106(28), 11546-11551. doi:10.1073/pnas.0905222106

26. Li, S., Liu, C., Li, N., Hao, T., Han, T., Hill, D. E., . . . Lin, J. D. (2008). Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism. Cell Metab, 8(2), 105-117. doi:10.1016/j.cmet.2008.06.013

27. Zhao, W., Feng, D., Sun, S., Han, T., & Sui, S. (2010). The anti-viral protein of trichosanthin penetrates into human immunodeficiency virus type 1. Acta Biochim Biophys Sin (Shanghai), 42(2), 91-97.