王建伟，正高级研究员，博导，青年千人

E-mail: wangjianwei@ihcams.ac.cn

2024.02-现在  中国医学科学院血液病医院研究员 2021.1-2024.01 清华大学药学院副教授

2016.1-2020.12  清华大学药学院 tenure track 助理教授 2013.1-2015.12 德国莱布尼兹衰老研究所博士后

2012.3-2012.12  德国 Ulm 大学博士后

2007.9-2012.2   德国 Ulm 大学博士研究生

2003.9-2007.6   中国协和医科大学硕士研究生（阜外心血管病 医院）

1998.9-2002.7   北京航空航天大学电子工程系学士

主要科研领域与方向：

王建伟博士，2002 年本科毕业于北京航空航天大学电子工程系，2006 年硕士毕业于中国协和医科 大学，于 2012 年在德国乌尔姆大学获得博士学位。王建伟博士入选 2016 年度国家级人才计划， 并加入清华大学药学院成为独立研究员（Principle Investigator），2024 年 2 月加入中国医学科学院 血液病开展后续研究和临床转化工作。

王建伟研究员长期从事造血干细胞干性维持、衰老以及相关血液疾病研究工作，在造血干细胞衰 老领域取得了一系列的研究成果，包括阐明了 B 细胞激活转录因子 Batf 调控造血干细胞衰老的分 子机制（Wang J.W. et al. Cell, 2012），发现节律调控基因 Per2 在造血干细胞淋系分化中的关键功能 （Wang J.W. et al. Nat. Cell. Biol., 2016），从分子层面解析了衰老的造血干细胞累积 DNA 损伤的分子 机制（Wang J.W. et al. BLOOD, 2014）。长期以来，衰老领域科学家普遍认为 DNA 累积的物理损伤是 导致细胞和组织器官功能发生退行性变化的关键驱动因素。然而，仅通过标志物来判定 DNA 损伤 缺乏更直观的数据支持；另外，造血干细胞内 DNA 损伤触发的导致其功能耗竭的分子事件也不明 确。自从 2016 年初独立开展科研工作以来，王建伟研究员致力于回答上述科学问题并取得重要突 破。王建伟研究员团队发现衰老的造血干细胞并未累积传统意义上的 DNA 损伤，损伤信号源于基 因组结构变化，包括染色质、区室、TAD 和更小尺度的基因组结构（BLOOD, 2024）。在初步破解了 DNA 损伤信号来源后，王建伟教授追问 DNA 损伤信号会触发哪些级联反应而导致 HSC 衰老。通过深 入研究，王建伟教授团队发现 DNA 损伤信号导致泛素化和乙酰化通路异常，进而引发 MCPH1 核质 分布失衡以及 TRMT6/TRMT61A 复合物和 PUS10 异常累积，最终激活程序性坏死导致其衰老（Nature Aging, 2024a, 2024b; Haematologica, 2023）。由于程序性坏死的发生会伴随炎症，王建伟教授于是探 究造血干细胞响应炎症信号的关键基因。通过大规模筛选，王建伟教授团队鉴定出造血干细胞响 应炎症信号的传感器基因 IL27Ra，并证实靶向干预 IL27Ra 改善衰老造血干细胞功能（BLOOD, 2020）。同时，王建伟教授团队证明炎症微环境是导致血液系统发生克隆性增生的关键驱动因素， 并筛选出抑制该过程的小分子（Acta Pharmaceutica Sinica B, 2021 ；Cell Death Discovery, 2021）。课题组同时发现 RNA m6A 识别蛋白Ythdf3 修饰通过解码基因 Ccnd1 的 m6A 信号调控造血干细胞功能 （Haematologica, 2022）

发表论文（#通讯作者，*共同第一作者）：

1. Baixue Tang, Xinming Wang, Yang Yang, Guofeng Qiao, Zihan Xu, Longteng Wang, Zhangbin Bao, Qiongye Dong, Yi Lin, Jia Yu, Michael Q. Zhang#, Minglei Shi#, Jianwei Wang#. Aging-disturbed FUS Phase Transition Impairs Hematopoietic Stem Cell by Altering Chromatin Structure. BLOOD, 2024

2. Hanqing He, Yuqian Wang, Xiaoting Zhang, Xiaoyu Li,  Chao Liu, Dingfei Yan, Haiteng Deng, Chengqi Yi#, Jianwei Wang#. Aging-elevated noncanonical TRMT6/61A signaling Impairs Hematopoietic Stem Cells. Nature Aging, 2024

3. Hanqing He, Yuqian Wang, Baixue Tang, Qiongye Dong, Chou Wu, Jianwei Wang#. Aging-induced MCPH1 Translocation Impairs Hematopoietic Stem Cells by Activating Necroptosis. Nature Aging, 2024

4. Min Liao, Ruiqing Chen, Yang Yang, Hanqing He, Liqian Xu, Yuxuan Jiang, Zhenxing Guo, Wei He, Hong Jiang#, Jianwei Wang#. Aging-elevated Inflammation Promotes DNMT3A R882H-driven Clonal Hematopoiesis. Acta Pharmaceutica Sinica B. 2022; 12(2):678-691.

5. Min Liao, Qiongye Dong, Ruiqing Chen, Liqian Xu, Yuxuan Jiang, Zhenxing Guo, Min Xiao, Wei He, Changcai Cao, Ronghua Hu, Wanling Sun#, Hong Jiang#, Jianwei Wang#. Oridonin inhibits DNM3A R882 mutation-driven clonal hematopoiesis and leukemia by inducing apoptosis and necroptosis. Cell Death Discovery. 2021; 7 (1): 297.

6. Hanqing He, Panglian Xu , Xiaofei Zhang , Min Liao , Qiongye Dong , Tingting Cong , Baixue Tang , Xiuxiu Yang , Maoqing Ye , Ying-Jun Chang , Weihua Liu, Xiaowo Wang, Zhenyu Ju, Jianwei Wang#. Aging-induced IL27Ra Signaling Impairs Hematopoietic Stem Cells. BLOOD. 2020;136(2):183-198.

7. Xiaofei Zhang, Tingting Cong, Lei Wei, Bixi Zhong, Xiaowo Wang, Jin Sun, Shuxia Wang, Meng Michelle Xu, Ping Zhu#, Hong Jiang#, Jianwei Wang#. YTHDF3 Modulates Hematopoietic Stem Cells by Recognizing RNA m6A Modification on Ccnd1. Haematologica, 2022 Oct1; 107(10): 2381–2394

8. Yuqian Wang, Zhenzhen Zhang, Hanqing He, Jinghui Song, Yang Cui, Yuan Zhuang, Xiaoting Zhang, Michael Q.Zhang#, Minglei Shi#, Chengqi Yi#, Jianwei Wang#. Aging-increased Pseudouridine Synthase 10 Impairs Hematopoietic Stem Cells. Haematologica, 2023 Oct 1; 108(10): 2677–2689.

9. Wenjing Li, Haiwei Liang, Yanxiao Ao, Baixue Tang, Junyang Li, Ning Li, Jianwei Wang#, and Yanan Du#. Biophysical cues of marrow-inspired scaffold regulate hematopoiesis of hematopoietic stem and progenitor cells. Biomaterial, 2023

10. Xiuxiu Yang, Liang Ge, Jianwei Wang#. BECN1 modulates hematopoietic stem cells by targeting Caspase-3-GSDME-mediated pyroptosis. BLOOD Science. 2020;2(3):89-99.

11. Hanqing He, Yuqian Wang, Jianwei Wang#. ALKBH3 is dispensable in maintaining hematopoietic stem cells but forced ALKBH3 rectified the differentiation skewing of aged hematopoietic stem cells. BLOOD Science. (2020)2, 137-143.

12. Min  Liao, Jianwei Wang#. Tcf12 balances the reconstitution and differentiation capacity of hematopoietic stem cell. BLOOD Science. (2021)3, 14-19.

13. Xiuxiu Yang, Tingting Cong, Hanqing He, Jianwei Wang#. GSDME maintains Hematopoietic Stem Cells by Balancing Pyroptosis and Apoptosis. BLOOD Science. (2021) 3, 40-47.

14. Min Liao & Jianwei  Wang#. Mechanisms of hematopoietic stem cell ageing and targets for hematopoietic tumour prevention. Adv. Exp. Med. Biol. 2018;1086:117-140.

15. Tingting Cong, Yuqian Wang, Jianwei Wang#. GSDMD is dispensable in modulating hematopoietic homeostasis and hematopoietic stem cell function. Life Medicine, 2023.

16. Jianwei Wang, Yohei Morita, Bing Han and Karl Lenhard Rudolph. Per2 induction limits lymphoid- biased hematopoietic stem cells and immune function in the context of DNA damage and aging. Nat Cell Biol. 2016 May;18(5):480-90

17. Jianwei Wang, Xin Lu, Vadim Sakk, Christoph A. Klein, and Karl Lenhard Rudolph. Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres. Blood. 2014 Nov 20;124(22):3237-40.

18. Tobias Sperka*, Jianwei Wang* & K. Lenhard Rudolph. DNA damage checkpoints in stem cells, aging and cancer. Nature Reviews Molecular Cell Biology. 2012; 23:579-590. (*Equal contribution)

19. Jianwei Wang, Qian Sun, Yohei Morita,Hong Jiang,,,K.Lenhard  Rudolph.A differentiation checkpoint limiting hematopoietic stem cell self-renewal in response to DNA damage. Cell. 2012;148(5):1001-1014.

20. Jianwei Wang, Hartmut Geiger, K. Lenhard Rudolph. Immunoaging induced by hematopoietic stem cell aging. Current Opinion in Immunology. 2011;23(4):532-536.

21. Jianwei Wang*, Hu Wang*, Jingzhou Chen, Xiaojian Wang, Kai Sun, Yibo Wang, Jizheng, Hui Rutai. GADD45B Inhibits MKK7-induced Cardiac Hypertrophy and is Associated with Hypertropic Cardiomyopathy. Biochem Biophys Res Commun. 2008; 372(4):623-628. (*Equal contribution)

22. Zhangfa Song, Jianwei Wang, Luis Miguel Guachalla, Grzegorz Terszowski, Hans-Reimer Rodewald, Zhenyu Ju, and K. Lenhard Rudolph. Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice. BLOOD. 2010;115(8):1481148-9.

23. Hong Jiang, Eric Schiffer, Zhangfa Song, Jianwei Wang, Petra Zürbig, Kathrin Thedieck, Suzette Moes, Heike Bantel, Nadja Saal, Justyna Jantos, Meiken Brecht, Paul Jenö, Michael N. Hall, Klaus Hager, Michael P. Manns, Hartmut Hecker, Arnold Ganser, Konstanze Döhner, Andrzej Bartke, Christoph Meissner, Harald Mischak, Zhenyu Ju, and K. Lenhard Rudolph. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc Natl Acad Sci U S A. 2008;105(32):11299–04.