韓霆博士

北京生命科學(xué)研究所高級研究員

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

Phone: 86-10-80726688

Fax: 86-10-80726689

E-mail:hanting@nibs.ac.cn

教育經(jīng)歷

Education

2006年 清華大學(xué) 生物學(xué)學(xué)士學(xué)位

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

2013年 美國密西根大學(xué)細(xì)胞和發(fā)育生物學(xué)博士

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

工作經(jīng)歷

Professional Experience

2025 - 北京生命科學(xué)研究所高級研究員

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

2017 - 2024 北京生命科學(xué)研究所研究員

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

2013 - 2017 美國德克薩斯大學(xué)西南醫(yī)學(xué)中心博士后

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

研究概述

Research Description:

我們實(shí)驗室的研究聚焦于化學(xué)生物學(xué)和癌癥生物學(xué)兩個互補(bǔ)領(lǐng)域，交匯點(diǎn)在于開發(fā)創(chuàng)新的癌癥治療策略。我們的目標(biāo)是應(yīng)對生物醫(yī)學(xué)中的兩大核心挑戰(zhàn)：（1）缺乏通用方法來有效調(diào)控大多數(shù)致病蛋白；（2）可支持未來治療創(chuàng)新的新靶點(diǎn)逐漸枯竭。在過去的幾年中，我們通過“化學(xué)驅(qū)動”和“生物驅(qū)動”兩種方法，在這些領(lǐng)域取得了進(jìn)展。“化學(xué)驅(qū)動”的方法以基于表型的高通量篩選為起點(diǎn)，尋找具有選擇性抗癌活性的小分子，并進(jìn)一步解析其作用機(jī)制。“生物驅(qū)動”的方法通過體內(nèi)CRISPR篩選，揭示腫瘤內(nèi)在的免疫逃逸機(jī)制。這些研究不僅深化了我們對癌癥生物學(xué)的認(rèn)識，還提供了開發(fā)抗癌療法的新靶點(diǎn)和化學(xué)起點(diǎn)。
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.

發(fā)表論文

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.