陈则宇
助理教授，研究员，博士生导师

北京大学基础医学院
地址：北京市海淀区学院路38号
北京大学医学部中心实验楼707

个人邮箱：zeyuchen@hsc.pku.edu.cn

教育及工作经历

2009.08-2013.06 北京大学生命科学学院（邓宏魁组），本科生，2013年获学士学位

2013.08-2014.05 耶鲁大学医学院（Richard A. Flavell组），科研助理

2014.08-2020.10 宾夕法尼亚大学医学院（E. John Wherry组），博士生，2020年获博士学位

2020.11-2025.03 哈佛大学医学院/博德研究所（Bradley E. Bernstein组），博士后

2025.04 至今 北京大学基础医学院，助理教授/研究员

研究方向

免疫基因的调控异常，与多种人类重大疾病紧密相关。T细胞作为效应性免疫系统中的核心细胞类型，研究其转录调控和表观遗传层面上的系统性变化，对于理解T细胞在不同人群、不同生理和病理微环境下，对于外界信号的特异性响应机制，并将其运用于改造和设计全新的细胞疗法，具有核心意义。

本实验室聚焦于T细胞转录调控的遗传编码解析及其工程化研究，拟开发和利用新型分子生物学和计算生物学工具，包括新型单碱基编辑系统，哺乳动物原位定向进化系统，基因组大语言模型模拟突变，生成式人工智能等，目标在原代T细胞上探究如下两个方向：1）解析基因组上碱基突变对于免疫基因调控功能的预测，进而理解人类遗传多态性如何影响人类免疫健康；2）突破自然进化基因组的调控瓶颈，建立生成式T细胞转录环路体系，进而实现病理微环境特异性的精准医疗。

成果和荣誉奖励
     共发表论文三十余篇，其中以一作/共同一作在Cell, Science, Immunity, Cell Genomics, Nature Reviews Immunology等期刊上发表论文6篇，总引用8000+，H-index 29，共6篇论文入选ESI高被引论文系列，获批两项国际专利（US Patent App. 18/547,445, US Patent App. 18/566,410）。
入选国家级海外人才项目，曾获得国家优秀自费留学生奖学金，国家奖学金，美国国立卫生院F99/K00奖学金，北京大学优秀校友工作奖等奖项。

第一/共同第一作者文章

1. Xi Dawn Chen*, Zeyu Chen*, Benno C. Orr, Yifan Zhang, George Wythes, Gary Sun, Ka Thao, Mehdi Borji, Mounica Vallurupalli, Jing Sun, Haiqi Chen, Bradley E. Bernstein#, Fei Chen#. Helicase- assisted continuous editing for targeted endogenous mutagenesis. Science, 2024.

2. Zeyu Chen*, Nauman Javed*, Molly Moore, Jingyi Wu, Gary Sun, Michael Vinyard, Alejandro Collins, Luca Pinello, Fadi J Najm#, Bradley E Bernstein#. Integrative dissection of gene regulatory elements at base resolution. Cell Genomics, 2023

3. Zeyu Chen, Eri Arai, Omar Khan, Zhen Zhang, Shin Foong Ngiow, Yuan He, Hua Huang, Sasikanth Manne, Zhendong Cao, Amy E. Baxter, Zhangying Cai, Elizabeth Freilich, Mohammed A. Ali, Josephine R. Giles, Jennifer E. Wu, Allison R. Greenplate, Mohamed A. Hakeem, Qingzhou Chen, Makoto Kurachi, Kito Nzingha, Viktoriya Ekshyyan, Divij Mathew, Zhuoyu Wen, Nancy A. Speck, Alexis Battle, Shelley L. Berger, E. John Wherry#, and Junwei Shi. In vivo CRISPR screening reveals control by Fli1 in infection and cancer. Cell, 2021

4. Zeyu Chen, E. John Wherry. T cell response in patients with COVID-19. Nature Reviews Immunology, 2020

5. Zeyu Chen*, Zhicheng Ji*, Shin Foong Ngiow, Sasikanth Manne, Zhangying Cai, Alexander C. Huang, John Johnson, Ryan P. Staupe, Bertram Bengsch, Caiyue Xu, Sixiang Yu, Makoto Kurachi, Ramin S. Herati, Laura A. Vella, Amy E. Baxter, Jennifer E. Wu, Omar Khan, Jean- Christophe Beltra, Josephine R. Giles, Erietta Stelekati, Laura M. McLane, Chi Wai Lau, Xiaolu Yang, Shelley L. Berger, Golnaz Vahedi, Hongkai Ji, E. John Wherry. TCF-1-centered transcriptional network drives an effector versus exhausted CD8 T cell-fate decision. Immunity, 2019

6. Zeyu Chen*, Erietta Stelekati*, Makoto Kurachi, Sixiang Yu, Zhangying Cai, Sasikanth Manne, Omar Khan, Xiaolu Yang, E.John Wherry. MiR-150 regulates memory CD8 T cell differentiation via c-Myb. Cell Reports, 2017

近期部分其他文章

7. Tyler E. Miller*, Chadi Abdul Kader El Farran*, Charles P. Couturier*, Zeyu Chen, Joshua P. D'Antonio, Julia Verga, Martin A Villanueva, L Nicolas Gonzalez Castro, Yuzhou Evelyn Tong, Tariq Al- Saadi, Andrew N. Chiocca, David S. Fischer, Dieter Henrik Heiland, Jennifer L. Guerriero, Kevin Petrecca, Mario L Suva, Alex K. Shalek, Bradley E. Bernstein. Programs, Origins, and Niches of Immunomodulatory Myeloid Cells in Gliomas. Nature, 2025

8. Shin Foong Ngiow, Sasikanth Manne, Yinghui Jane Huang, Tarek Azar, Zeyu Chen, Divij Mathew, Qingzhou Chen, Omar Khan, Jennifer E Wu, Victor Alcalde, Ahron J Flowers, Sean McClain, Amy E Baxter, Makoto Kurachi, Junwei Shi, Alexander C Huang, Josephine R Giles, Arlene H Sharpe, Dario AA Vignali, E John Wherry. LAG-3 sustains TOX expression and regulates the CD94/NKG2-Qa-1b axis to govern exhausted CD8 T cell NK receptor expression and cytotoxicity, Cell, 2024.

9. Cody T. Mowery, Jacob W. Freimer, Zeyu Chen, Salvador Casaní-Galdón, Jennifer M. Umhoefer, Maya M. Arce, Ketrin Gjoni, Bence Daniel, Katalin Sandor, Benjamin G. Gowen, Vinh Nguyen, Dimitre R. Simeonov, Christian M. Garrido, Gemma L. Curie, Ralf Schmidt, Zachary Steinhart, Ansuman Satpathy, Katherine S. Pollard, Jacob E. Corn, Bradley E Bernstein, Chun Jimmie Ye* & Alexander Marson*. Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells. Nature Genetics, 2024

10. Zhen Zhang, Amy E. Baxter, Diqiu Ren, Kunhua Qin, Zeyu Chen, Sierra M. Collins, Hua Huang, Chad A. Komar, Peter F. Bailer, Jared B. Parker, Gerd A. Blobel, Rahul M. Kohli, E. John Wherry, Shelley L. Berger, Junwei Shi. Efficient engineering of human and mouse primary cells using peptide- assisted genome editing. Nature Biotechnology, 2023

11. Amy E. Baxter, Hua Huang, Josephine R. Giles, Zeyu Chen, Jennifer E. Wu, Sydney Drury, Katherine Dalton, Simone L. Park, Leonel Torres, Brandon W. Simone, Max Klapholz, Shin Foong Ngiow, Elizabeth Freilich, Sasikanth Manne, Victor Alcalde, Viktoriya Ekshyyan, Shelley L. Berger, Junwei Shi, Martha S. Jordan and E. John Wherry, SWI/SNF chromatin remodeling complexes BAF and PBAF have distinct roles in regulating progenitor versus non- progenitor exhausted CD8 T cells. Immunity, 2023.

12. Sofia Battaglia, Kevin Dong, Jingyi Wu, Zeyu Chen, Vivian Hecht, Noam Shoresh, Fadi Najm , Molly Moore, Yuanyuan Zhang, Bradley Bernstein. Phased epigenomic profiles deconvolve dynamic immune loci and a classical imprinted region, Nature Genetics, 2022.

13. Mohamed S. Abdel-Hakeem, Sasikanth Manne, Jean-Christophe Beltra, Erietta Stelekati, Zeyu Chen, Kito Nzingha, Mohammed-Alkhatim Ali, John L. Johnson, Josephine R. Giles, Divij Mathew, Allison R. Greenplate, Golnaz Vahedi, E. John Wherry. Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation. Nature Immunology, 2021

14. Jonathan B. Johnnidis, Yuki Muroyama, Shin Foong Ngiow, Zeyu Chen, Sasikanth Manne, Zhangying Cai, Shufei Song, Jesse M. Platt, Jason M. Schenkel, Mohamed Abdel-Hakeem, Jean- Christophe Beltra, Allison R. Greenplate, Mohammed-Alkhatim A. Ali, Kito Nzingha, Josephine R. Giles, Christelle Harly, John Attanasio, Kristen E. Pauken, Bertram Bengsch, Michael A.Paley, Vesselin T. Tomov, Makoto Kurachi, Dario A. A. Vignali, Arlene H. Sharpe, Steven L. Reiner, Avinash Bhandoola, F. Bradley Johnson, E. John Wherry. Inhibitory signaling sustains a distinct early memory CD8+ T cell precursor that is resistant to DNA damage. Science Immunology, 2021

15. Divij Mathew, Josephine R. Giles, Amy E. Baxter, Derek A. Oldridge, Allison R. Greenplate, Jennifer E. Wu, Cécile Alanio, Leticia Kuri-Cervantes, M. Betina Pampena, Kurt D’Andrea, Sasikanth Manne, Zeyu Chen, Yinghui Jane Huang, John P. Reilly, Ariel R. Weisman, Caroline AG Ittner, Oliva Kuthuru, Jeanette Dougherty, Kito Nzingha, Nicholas Han, Justin Kim, Ajinkya Pattekar, Eileen C Goodwin, Elizabeth M Anderson, Madison E Weirick, Sigrid Gouma, Claudia P Arevalo, Marcus J Bolton, Fang Chen, Simon F. Lacey, Holly Ramage, Sara Cherry, Scott E. Hensley, Sokratis A. Apostolidis, Alexander C. Huang, Laura A. Vella, Michael R. Betts, Nuala J. Meyer, E. John Wherry. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications, Science, 2020.

16. Marcus Buggert, Laura A. Vella, Son Nguyen, Vincent H. Wu, Zeyu Chen, Takuya Sekine, André Perez-Potti, Colby R. Maldini, Sasikanth Manne, Samuel Darko, Amy Ransier, Leticia Kuri- Cervantes, Alberto Sada Japp, Irene Bukh Brody, Martin A. Ivarsson, Jean-Baptiste Gorin, Olga Rivera-Ballesteros, Laura Hertwig, Jack P. Antel, Matthew E. Johnson, Afam Okoye, Louis Picker, Golnaz Vahedi, Ernesto Sparrelid, Sian Llewellyn-Lacey, Emma Gostick, Johan K. Sandberg, Niklas Björkström, Amit Bar-Or, Yoav Dori, Ali Naji, David H. Canaday, Terri M. Laufer, Andrew D. Wells, David A. Price, Ian Frank, Daniel C. Douek, E. John Wherry, Maxim G. Itkin, Michael R. Betts. The identity of human tissue-emigrant CD8+ T cells, Cell, 2020.

17. Jean-Christophe Beltra, Sasikanth Manne, Mohamed S. Abdel-Hakeem, Makoto Kurachi, Josephine R. Giles, Zeyu Chen, Valentina Casella, Shin Foong Ngiow, Omar Khan, Yinghui Jane Huang, Patrick Yan, Kito Nzingha, Alexander C. Huang, E. John Wherry. Developmental relationships of four exhausted CD8 T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity, 2020.