朱书

研究方向：

机体免疫系统如何识别自我非我的抗原是免疫学的核心问题。机体发展了针对自我抗原的中枢耐受机制避免免疫系统攻击自身抗原（1960年诺贝尔生理与医学奖）。针对非我抗原，免疫系统已经发展出感知病原信号并启动免疫激活和清除机制的系统（2011年诺贝尔生理与医学奖）。肠道是人体极为特殊也是最大的粘膜免疫器官，聚集了全身一半以上的免疫细胞，来应对大量偶发性的病原细菌病毒感染，以及持续存在的共生微生物和食物抗原等。其中，共生微生物、食物等非我共生物质如何被识别并启动免疫稳态或者耐受的生理机制，以及该过程失调导致的疾病机制还有诸多未知。我们课题组在肠道免疫识别方向近几年以通讯作者发表了一系列工作：

1.解析肠道上皮细胞特异表达受体NLRP6感知肠道病毒来源的dsRNA并形成相分离高效整合IL-18/IFN等信号维持免疫稳态的机制（Cell 2021；Science Advance 2023；PNAS 2024）；

2.发现肠道上皮细胞NLR下游效应分子GSDMD响应食物抗原刺激剪切入核转录MHCII从而诱导Tr1介导的免疫耐受（Cell 2023），并发现缺乏大分子蛋白质的氨基酸食物长期喂食会导致肠道微生物紊乱以及抑郁样行为Cell Reports 2024）。

3.鉴定肠道上皮细胞及免疫细胞多个受体（PMCA，AHR，ADRA2A）感知共生微生物异常产生的代谢产物小分子（DCA，IDA，Tyramine）抑制正常生理过程（CTL killing，IEC ferroptosis，ISC proliferation）促进肠癌或肠炎发病的机制（Immunity 2024；Nature Cell Biology 2024；Cell Host Microbe 2024）；并开发不破坏肠道微生物的抗生素递送新方法(Nature Biomedical Engineering 2022) 。

实验室将进一步围绕肠道微环境中免疫系统、微生物、食物之间的互作展开研究及临床应用工作。

个人简介：

国家杰青。曾获中组部创新人才计划，基金委优青、MIT 35 Innovators under 35 China，求是杰出青年学者奖，中源协和创新突破奖等。研究方向为肠道微生物的免疫识别和免疫调控，以及微生物及免疫新疗法。发表文章70余篇，近5年以通讯作者在Cell（2023，2021），Immunity（2024），Nature Biomedical Engineering（2022），Cell Research (2023)，PNAS (2024，2021)，Science Advance (2023)，Cell Reports (2024，2022)，Nature Reviews Gastroenterology & Hepatology（2022）等杂志发表研究和综述论文。总引用8000余次，H index 39。Nature、Cell、Immunity、Lancet、PNAS、Gut等杂志审稿人。以第一发明人申请国家发明专利28项，PCT专利7项，获批发明专利7项，3个项目已获得批件进入研究者发起的临床试验阶段。

实验室网页：http://zhulab.ustc.tsg211.com/

联系方式：zhushu@ustc.tsg211.com 

电话：0551-63600317

OCRID ID: 0000-0002-8163-0869

教育和研究经历：

2002-2006年，图书馆VIP生命科学学院，获学士学位

2006-2012年，上海生命科学研究院健康科学研究所，获细胞生物学博士学位

2012-2017年，美国耶鲁大学医学院免疫学系，博士后

2017年  至今，图书馆VIP生命科学与医学部，教授博导

获奖情况： 

2006年  郭沫若奖学金

2011年  中科院院长优秀奖

2011年  强生亚洲优秀研究生论文奖

2012年  中科院院长特别奖

2012年  吴瑞奖学金

2012年  中科院百篇优博论文

2014年  Helen-Hay Whitney-HHMI Fellowship

2017年  中组部创新人才计划

2018年  MIT Technology Review 35 Innovators Under 35（MIT TR35 China）

2018年  求是杰出青年学者

2018年  基金委优青

2022年  中源协和创新突破奖

2023年  基金委杰青

发表论文：(*第一作者，#通迅作者)

2024

1. Cong J*, Liu P*, Han Z*, Ying W, Li C, Yang J, Song X, Dai L, Sun L, Kasper D, Pan W^#, Zhu S^#. Bile acids modified by the microbiota suppress gut anti-tumor immune responses. Immunity. 2024 Mar 6:S1074-7613(24)00090-6. doi: 10.1016/j.immuni.2024.02.014. (IF=43.5)

2. Li C, Zhang P, Xie Y, Wang S, Guo M, Wei X, Zhang K, Cao D, Zhou R, Wang S, Song X^#, Zhu S^#, Pan W^#. Enterococcus-derived tyramine hijacks α2A-adrenergic receptor in intestinal stem cells to exacerbate colitis. Cell Host Microbe. 2024 May 21:S1931-3128(24)00140-9. doi: 10.1016/j.chom.2024.04.020. (IF=30.1)

3. Zhu S^#, Pan W^#. Microbial metabolite steers intestinal stem cell fate under stress. Cell Stem Cell. doi.org/10.1016/j.stem.2024.04.006. (IF=23.9)

4. Ren X, Liu Q, Zhou P, Zhou T, Wang D, Mei Q, Flavell RA, Liu Z^#, Li M^#, Pan W^#, Zhu S^#. DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells. Nature Communications. 2024 Apr 9;15(1):3080. doi: 10.1038/s41467-024-47235-2. (IF=16.6)

5. Hu J*, He K*, Yang Y*, Huang C, Dou Y, Wang H, Zhang G, Wang J, Niu C, Bi G, Zhang L^#, Zhu S^#. Amino-acid formula induces microbiota dysbiosis and contributes to depressive-like behavior. Cell Reports. 2024 Feb 26;43(3):113817.doi: 10.1016/j.celrep.2024.113817. (IF=10.0)

6. Li R*, Zan Y*, Wang D, Chen X, Wang A, Tan H, Zhang G, Ding S, Shen C^#, Wu H^#, Zhu S^#. A mouse model to distinguish NLRP6-mediated inflammasome-dependent and independent functions. PNAS. 2024 Feb 6;121(6):e2321419121. doi: 10.1073/pnas.2321419121. (IF=11.1)

7. W Cui, M Guo, D Liu, Y Zhang, J Cong, Z Han, Y Yang, J Liu, C Liang, S Shi, P Xiao, C Yang, H Huang, X Fu, Y Xu, L Du, C Yin, Y Zhang, J Sun, R Chai^#, W Gu^#, S Zhu^#, B Chu^#. Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition. Nature Cell Biology. 26, 124–137 (2024). (IF=28.2)

2023

8. K He*, T Wan*, D Wang*, J Hu*, T Zhou, W Tao, Z Wei, Q Lu, R Zhou, Z Tian, R Flavell^#, and S Zhu^#. Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine. Cell. 2023 Jun 9;S0092-8674(23)00577-9. doi: 10.1016/j.cell.2023.05.027. (IF=66.9)

Comment in:

Trends in Immunology. 2023 Aug;44(8):571-573. doi: 10.1016/j.it.2023.06.006. Chopped! Newfound GSDMD cleavage facilitates tolerance to food allergens.

Cell Research. 2023 Dec;33(12):896-897. doi: 10.1038/s41422-023-00856-6. Cleaving an epithelial path to food tolerance.

Gastroenterology. doi:10.1053/j.gastro.2023.08.024. Tolerance to Dietary Antigens in the Upper Intestine Through Chopping of Gasdermin D.

Allergy. doi: 10.1111/all.16076. Insights in intestinal immune tolerance: The role of the cleavage form of gasdermin D.

8. T Wan*, Y Wang*, K He*, S Zhu^#. Microbial sensing in the intestine. Protein & Cell, pwad028, 2023. doi.org/10.1093/procel/pwad028. (IF=15.3)

9. H Ma*, T Hu*, W Tao, J Tong, Z Han, D Herndler-Brandstetter, Z Wei, X Xu, K Zhang, R Liu, T Zhou, Q Liu, J Cho, HB Li^#, H Huang^#, R Flavell^#, and Zhu S^#. A lncRNA from an inflammatory bowel disease risk locus maintains intestinal host-commensal homeostasis. Cell Research. 2023, doi.org/10.1038/s41422-023-00790-7. (IF=46.3)

10. X Ren, D Wang, G Zhang, T Zhou, Z Wei, Y Yang, Y Zheng, X Lei, W Tao, A Wang, M Li^#, R Flavell^#,Zhu S^#. Nucleic DHX9 Cooperates with STAT1 to Transcribe Interferon-Stimulated Genes. Science Advance. 2023, DOI: 10.1126/sciadv.add5005 (IF=14.1)

11. X Wang*, C Chen*, H Sun*, K Mao*, J Yao, W Zhang, M Zhan, H-B Li, Z Zhang^#, S Zhu^#, L Lu^#. m6A mRNA modification potentiates Th17 functions to inflame autoimmunity. Sci. China Life Sci. (2023). https://doi.org/10.1007/s11427-022-2323-4. (IF=10.4)

12. Liu Z, Liu R, Gao H, Jung S, Gao X, Sun R, Liu X, Kim Y, Lee HS, Kawai Y, Nagasaki M, Umeno J, Tokunaga K, Kinouchi Y, Masamune A, Shi W, Shen C, Guo Z, Yuan K; FinnGen; International Inflammatory Bowel Disease Genetics Consortium; Chinese Inflammatory Bowel Disease Genetics Consortium; Zhu S, Li D, Liu J, Ge T, Cho J, Daly MJ, McGovern DPB, Ye BD, Song K, Kakuta Y, Li M, Huang H. Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries. Nature Genetics. 2023 May;55(5):796-806. doi: 13.1038/s41588-023-01384-0. Epub 2023 May 8. PMID: 37156999; PMCID: PMC10290755. (IF=30.8)

14. Wang J, Zhao D, Lei Z, P Ge, Z Lu, Q Chai, Y Zhang, L Qiang, Y Yu, X Zhang, B Li, S Zhu, L Zhang^#, C Liu^#. TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal. Cell Mol Immunol 20, 158–174 (2023). https://doi.org/10.1038/s41423-022-00963-1. (IF=24.1)

2022

15. Zhang G*, Wang Q*, Tao W*, Jiang W, Elinav E, Wang Y^#, Zhu S^#. Glucosylated nanoparticles for the oral delivery of antibiotics to the proximal small intestine protect mice from gut dysbiosis. Nature Biomedical Engineering. 2022 Jul;6(7):867-881. doi: 10.1038/s41551-022-00903-4. (IF=29.2)

16. Chen C*, W Zhang*, T Zhou, Q Liu, C Han, Z Huang, S Chen, Q Mei, C Zhang, K Zhang, H Ma, R Zhou, W Jiang, Wen Pan, Zhu S^#. Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation. Cell Reports. 2022 Nov 29;41(9):111741. doi: 10.1016/j.celrep.2022.111741. (IF=10.0)

17. A Wang, W Tao, J Tong, J Gao, J Wang, G Hou, C Qian, G Zhang,R Li, D Wang, X Ren, K Zhang, S Ding, R Flavell, HB Li, W Pan^#, S Zhu^#.m6A modifications regulate intestinal immunity and rotavirus infection. Elife. 2022;11:e73628 DOI: https://doi.org/10.7554/eLife.73628 (IF=8.1)

18. Y Chen, X Wang, X Hao, B Li, W Tao, S Zhu, K Qu, H Wei, R Sun, H Peng, Z Tian. Ly49E separates liver ILC1s into embryo-derived and postnatal subsets with different functions. J Exp Med. 2022, 219(5): e20211805. (IF=17.58)

2021

19. Shen C*, Li R*, Negro R, Cheng J, Vora SM, Fu TM, Wang A, He K, Andreeva L, Gao P, Tian Z, Flavell RA, Zhu S^#, Wu H^#. Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome. Cell. 2021 Oct 20:S0092-8674(21)01115-6. doi:10.1016/j.cell.2021.09.032. (IF=41.6)

Comment in:

Cell Research. doi: 10.1038/s41422-021-00594-7. It’s just a phase: NLRP6 phase separations drive signaling.

21. M Guo*, W Tao*, R Flavell^#, and S Zhu^#. Potential intestinal infection and fecal–oral transmission of SARS-CoV-2. Nature Reviews Gastroenterology & Hepatology. 10.1038/s41575-021-00416-6 (IF=46.8)

22. Y Wang*, K He*, B Sheng*, X Lei, W Tao, X Zhu, Z Wei, R Fu, A Wang, S Bai, Z Zhang, N Hong, C Ye, Y Tian, J Wang, K Zhang, H Yang, L Li^#, H Li^#, R Flavell^#, S Zhu^#. The RNA helicase Dhx15 mediates Wnt-induced anti-microbial protein expression in Paneth cells. PNAS. 2021, 10.1073/pnas.2017432118 (IF=11.2)

23. Z Zhang*, G Zhang*, M Guo*, W Tao*, X Liu, H Wei, T Jin^#, Y Zhang^#, S Zhu^#. The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy. Pathogens. 2021, 10(7), 881. doi: 10.3390/pathogens10070881(IF=3.5)

24. J Tong, X Wang, Y Liu, X Ren, A Wang, Z Chen, J Yao, K Mao, T Liu, F Meng, W Pan, Q Zou, J Liu, Y Zhou, Q Xia^#, R Flavell^#, S Zhu^#, HB Li^#. Pooled CRISPR Screening Identifies m6A as a Positive Regulator of Macrophage Activation. Science Advance. 10.1126/sciadv.abd4742 (IF=14.1)

25. Y Chen, S Zhao, J Hu, C Han, X Lv, G Wang, S Wang, P Bo, J Zhang, W Wu, W Gui, Q Tang^#, Q Liu^#, S Zhu^#, F Yu^#. Increased accumulation of α-Synuclein in inflamed appendix of Parkinson’s disease patients. Movement Disorders. 2021 Apr 20. doi: 10.1002/mds.28553 (IF=10.3)

26. X Zheng, L Liu, G Meng, S Zhu, R Zhou^#, W Jiang^#.IL-18 maintains the homeostasis of mucosal immune system via inflammasome-independent but microbiota-dependent manner. Science Bulletin. Doi: 10.1016/j.scib.2021.01.025 (IF=11.8)

27. Song H, Song J, Cheng M, Zheng M, Wang T, Tian S, Flavell RA, Zhu S, Li HB, Ding C, Wei H, Sun R, Peng H, Tian Z. METTL3-mediated m6A RNA methylation promotes the anti-tumor immunity of natural killer cells. Nat Commun. 2021 Sep 17;12(1):5522. doi: 10.1038/s41467-021-25803-0. (IF=14.9)

28. G Xu, C Liu, S Zhou, Q Li, Y Feng, P Sun, H Feng, Y Gao, J Zhu, X Luo, Q Zhan, S Liu, S Zhu, H Deng, D Li, P Gao. Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion. Molecular Cell. doi.org/10.1016/j.molcel.2021.05.002 (IF=18.0)

29. H Han, Y Cao, C Feng, Y Zheng, S Zhu, C Shang, C Yuan, G Zong. Association of a Healthy Lifestyle with All-Cause and Cause-Specific Mortality Among Individuals with Type 2 Diabetes: A Prospective Study in UK Biobank Short Running. Diabetes Care. doi.org/10.2337/dc21-1512 (IF=19.1)