Genome Stability Maintenance, cGAS/STING Innate Immune Response,

RNA Surveillance, Cancer, Autoimmunity

zyou(at)cimrbj.ac.cn

B.S. in Biology, Zhejiang University, China

M.S. in Molecular Biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences, China

Ph.D. in Cell Biology, University of California, San Diego, USA

Work Experience

2025-Present

Investigator and Associate Director, Chinese Institute for Cancer Research, Chinese Institutes for Medical Research, Beijing, China

2025-Present

Adjunct Professor (Honorary), Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, USA

2023-2025

Professor, Department of Cell Biology and Physiology, Department of Medicine (secondary), Washington University in St. Louis, School of Medicine, USA

2017-2022

Associate Professor, Department of Cell Biology and Physiology, Department of Medicine (secondary), Washington University in St. Louis, School of Medicine, USA

2009-2016

Assistant Professor, Department of Cell Biology and Physiology, Department of Medicine (secondary), Washington University in St. Louis, School of Medicine, USA

2002-2009

Postdoc, Salk Institute for Biological Studies, USA

Honors and Awards

2013

American Cancer Society Research Scholar Award

2006

Young Investigator Award, Ataxia-Telangiectasia International Workshop

2005-2006

The Pioneer Fund Postdoctoral Fellowship

1993

Ke-zhen Zhu Scholarship

Research Interests

You Lab studies the molecular mechanisms of DNA/RNA surveillance and innate immune regulation. By integrating cell biology, structural biology, animal models, advanced imaging, and drug screening platforms, You Lab is pursuing four main research directions: (1) exploring the roles of ion channels in cGAS/STING-mediated innate immune responses; (2) elucidating key mechanisms of genome maintenance and their crosstalk with the innate immune system; (3) deciphering the functions and regulation of the nonsense-mediated mRNA decay (NMD) pathway; (4) developing novel therapeutic strategies and drugs for diseases such as cancer and autoimmune disorders based on lab's findings.

Major Contributions

1. Identified a novel cytosolic DNA-elicited, Ca²⁺-mediated signaling pathway that safeguards DNA replication forks to maintain genome stability (Mol Cell, 2019; Mol Cell, 2023; Nat Commun, 2024).

2. Uncovered a novel interplay on the endoplasmic reticulum between the ion channel TRPV2 and the innate immune factor STING, revealing a new mechanism that co-regulates Ca²⁺ dynamics and immune activation (Mol Cell, 2023; Cell Rep, 2026).

3. Pioneered the development of NMD reporter systems, leading to the identification of novel NMD inhibitors and genetic regulators, and demonstrated that NMD is modulated by intracellular Ca²⁺ and persistent DNA damage (Nat Med, 2014; J Biol Chem, 2017).

4. Identified NMD as a promising therapeutic target for cancers with spliceosome mutations (Cancer Res, 2021).

Representative Publications *：Co-first author; #：Co-corresponding author

Cheng C, Lu H-T, Li S and You Z. Dual Roles of TRPV2 in response to cytosolic DNA: arresting dormant and boosting activated STING. Cell Reports, 2026, 45: 116745. DOI: 10.1016/j.celrep.2025.116745

Kong L^*, Cheng C^*, Cheruiyot A, Yuan J, Yang Y, Hwang S, Foust D, Tsao N, Wilkerson E, Mosammaparast N, Major MB, Piston DW, Li S^#, You Z^#. TCAF1 Promotes TRPV2-mediated Ca²⁺ Release in Response to Cytosolic DNA to Protect Stressed Replication Forks. Nature Communications, 2024, 15: 4609. DOI: 10.1038/s41467-024-48988-6

Li S^*, Kong L^*, Meng Y, Cheng C, Lemacon DS, Yang Z, Tan K, Cheruiyot A, Lu Z and You Z . Cytosolic DNA Sensing by cGAS/STING Promotes TRPV2-Mediated Ca²⁺ Release to Protect Stressed Replication Forks. Molecular Cell, 2023, 83: 556-573. DOI: 10.1016/j.molcel.2022.12.034

Yang Z, Lemacon DS, Li S, Cheruiyot A, Kong L, Tan K, Cheng C, Turkay E, He D and You Z. A Context-dependent Pro- and Anti-resection Roles of ZKSCAN3 in Regulating Fork Resection during Replication Stress. Journal of Biological Chemistry, 2022, 29: 102215. DOI: 10.1016/j.jbc.2022.102215

Cheruiyot A^*, Li S^*, Nonavinkere SS, Ahmed T, Chen Y, Lemacon DS, Li Y, Tang Z, Wadugu BA, Warner WA, Pruett-Miller SM, Obeng EA, Lin DC, He D, Xiao F, Bailis JM, Walter MJ, You Z. Nonsense-mediated RNA Decay Is a Unique Vulnerability of Cancer Cells Harboring SF3B1 or U2AF1 Mutations. Cancer Research, 2021, 18: 4499-4513. DOI: 10.1158/0008-5472.CAN-20-4016

Li S, Lavagnino Z, Lemacon D, Kong L, Ustione A, Ng X, Zhang Y, Wang Y, Zheng B, Piwnica-Worms H, Vindigni A, Piston DW and You Z. Ca²⁺-stimulated AMPK-dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection. Molecular Cell, 2019, 74: 1123-1137. DOI: 10.1016/j.molcel.2019.04.003

Paudyal SC, Li S, Yan H, Hunter T and You Z. Dna2 Initiates Resection at Clean DNA Double-strand Breaks. Nucleic Acids Research, 2017, 45(20): 11766-11781. DOI: 10.1093/nar/gkx830

Nickless A, Cheruiyot A, Flanagan K, Piwnica-Worms, D, Stewart S and You Z. p38 MAPK Inhibits Nonsense-mediated RNA Decay in Response to Persistent DNA Damage in Non-cycling Cells. Journal of Biological Chemistry, 2017, 292: 15266-15276. DOI: 10.1074/jbc.M117.787846

Nickless A, Jackson E, Marasa J, Nugent P, Mercer RW, Piwnica-Worms D^# and You Z^#. Intracellular Calcium Regulates Nonsense-mediated mRNA Decay. Nature Medicine, 2014, 20: 961-966. DOI: 10.1038/nm.3620

Chen X, Paudyal SC, Chin RI, You Z. PCNA Promotes Processive DNA End Resection by Exo1. Nucleic Acids Research, 2013, 41: 9325-9338. DOI: 10.1093/nar/gkt672

You Z, Shi L, Zhu Q, Wu P, Zhang Y, Basilio A, Tonnu N, Verma I, Berns M and Hunter T^#. CtIP Links DNA Double-strand Break Sensing to Resection. Molecular Cell, 2009, 36: 954-969. DOI: 10.1016/j.molcel.2009.12.002