I am a Hundred Talents Program Researcher at Zhejiang University. I completed my Bachelor's degree in Veterinary Medicine at Jilin University and earned my Ph.D. in Molecular Cell and Genetic Medicine from the University of Copenhagen, Denmark. My research focuses on DNA damage repair and tumorigenesis, the interaction between viral infections and the host cell DNA damage response, and viral genome instability. My work aims to enhance therapeutic strategies for cancer and develop improved methods for combating viral infections.

1. Replication Stress and Genome Instability

DNA replication stress is one of the inevitable outcomes of oncogene activation during cancer development and is a key factor leading to genome instability, which drives tumor progression (Figure 1). However, excessive replication stress can lead to a "replication catastrophe," hindering tumor cell proliferation. Tumor cells have clearly evolved unique pathways to mitigate replication stress and rely on these pathways for survival, making the discovery and blockade of these pathways a promising strategy to halt cancer progression. Notably, drugs targeting replication stress regulators, such as ATR inhibitors M6620 and Berzosertib, have entered Phase I and II clinical trials, respectively. Preliminary results show significant inhibitory effects on advanced solid tumors. Therefore, research on replication stress regulators and pathways represents a frontier and a hot topic in the field of cancer molecular targeted therapy.

2. Molecular Mechanisms of Genome Stability in DNA Viruses

Research indicates that DNA viruses face significant replication stress during synthesis and may rely on certain proteins to alleviate this stress for effective DNA synthesis. Discovering and inhibiting these proteins could effectively block DNA virus replication. We aim to systematically identify proteins that stabilize viral DNA replication forks through techniques like iPOND-MS combined with single-molecule DNA fiber analysis and investigate their impact on viral genome stability. This research could help identify new targets for virus control and develop more effective prevention strategies.

3. Interaction Between Viruses and Host Cell DNA Damage Response (DDR)

Almost all viral infections can activate the host cell's DDR. On one hand, the host uses DDR to defend against viral infection; on the other hand, viruses can manipulate the host's DDR to facilitate their replication. Studying the interaction between viruses and the host DDR will help us identify new targets to inhibit viral replication.

研究工作以第一或通讯作者身份在Nature Structural & Molecular Biology，Nature Communications等期刊发表，以共同作者身份在Nature等期刊发表。

主持国家自然科学基金青年项目1项（项目名称：缓解癌基因激活诱导的DNA复制压力蛋白分子的筛选与功能分析；直接费用：30.00万元；项目起止年月：2022年01月至2024年12月）

主持国家自然科学基金面上项目1项（项目名称：p53非经典信号通路清除富含“未完全复制DNA”细胞的分子机制；直接费用：50.00万元；项目起止年月：2025年01月至2028年12月）

代表性论文：

1. Wei Wu#, Szymon Aleksander Barwacz, Marisa M. Gonçalves Dinis, Masato T. Kanemaki and Ying Liu#. 2022. Mitotic DNA synthesis in response to replication stress requires the sequential action of DNA polymerases zeta and delta in human cells. Nature Communications. # Corresponding author. Impact factor: 17.69 (第一作者+通讯作者) 

2. Wei Wu, Rahul Bhowmick, Ivan Vogel, Özgün Özer, Roshan S. Thakur, Philipp H. Richter, Liqun Ren, Ian D. Hickson and Ying Liu. 2020. RTEL1 Prevents The Pathological Accumulation Of R-Loops At Difficult-To-Replicate Loci In The Human Genome. Nature Structural & Molecular Biology. 27:424-437. Impact factor: 18.36

3. Sheroy Minocherhomji, Songmin Ying, Victoria A. Bjerregaard, Sara Bursomanno, Aiste Aleliunaite, Wei Wu, Hocine W. Mankouri, Huahao Shen, Ying Liu & Ian D. Hickson. 2015. Replication stress activates DNA repair synthesis in mitosis. Nature. 10; 528 (7581):286-90. Impact factor: 69.5