张悦正 博士生导师
云南省“兴滇英才”支持计划“青年人才”
Email：yuezhengzhang@gmail.com
个人简介：
2011年 中国科学院北京基因组研究所，博士学位；
2011-2015年 中国科学院北京基因组研究所，助理研究员；
2016-2019年University of Washington，博士后；
2019-2022年University of Washington，Acting instructor工作。
2022年5月 云南大学生命科学中心工作，研究员。
招生专业：
生物化学与分子生物学
生物信息学
研究方向：体细胞突变与癌症发生；癌症早诊与发生风险预测；衰老与癌症
癌症是一种由体细胞突变积累引发的衰老疾病。我们实验室致力于解析体细胞突变驱动的克隆演化机制，并探究环境因素如何加速这一过程并增加癌症风险。通过开发超灵敏突变检测技术，我们旨在识别癌症发生的早期分子事件和演化模式，为癌症的早期诊断、风险预测和个体化防治提供新策略。具体如下：
1. 正常组织中的克隆演化与癌变机制
· 解析体细胞突变积累的时空动态
· 探索克隆竞争与选择的分子机制
· 识别癌症发生的关键驱动事件
2. 衰老-环境-癌症的交互作用
· 基于“分子指纹”的环境致癌物检测
· 环境致癌物加速克隆演化的机制
3. 超灵敏检测技术开发与应用
· 低频突变检测技术
· 液体活检与循环肿瘤DNA分析
4. 临床转化研究
· 基于体细胞突变的癌症早期筛查
· 微小残留病灶（MRD）监测
· 个体化癌症风险评估模型
· 治疗反应预测与耐药监测
代表性研究成果：
1. Zhang, Y., Kohrn, B.F., Yang, M., Nachmanson, D., Soong, R., Lee, IH., Tao, Y., Clevers, H., Swisher, WM., Brentnall, TA., Loeb, LA., Kennedy, S.R., Salk, J.J., Naxevora, K., Risques, R.A. Risques (2021). PolyG-DS: An Ultra-Sensitive Polyguanine Tract Profiling Method to Detect Clonal Expansions and Trace Cell Lineage. Proceedings of the National Academy of Sciences, 2023373118. PMID: 34330826
2. Zhang, Y*., Li, Y*., Li, T*., Shen, X.*, Zhu, T., Tao, Y., Li, X., Wang, D., Ma, Q., and Hu, Z. (2019). Genetic load and potential mutational meltdown in cancer cell populations. Molecular biology and evolution 36, 541-552. PMID: 30649444
3. Zhang, Y., Zhang, L., Gao, Y., Li, C., Jia, S., Liu, N., Cheng, F., Niu, D., Cho, W.C., and Ji, J. (2011). Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling. World journal of gastroenterology: WJG 17, 1710. PMID: 214836313
4. Kennedy, S.R., Zhang, Y., and Risques, R.A. (2019). Cancer-associated mutations but no cancer: insights into the early steps of carcinogenesis and implications for early cancer detection. Trends in cancer 5, 531-540. PMID: 31474358
5. Li, T., Liu, J., Feng, J., Liu, Z., Liu, S., Zhang, M., Zhang, Y., Hou, Y., Wu, D., and Li, C. (2021). Variation in the life history strategy underlies functional diversity of tumors. National Science Review 8, nwaa124.
6. Krimmel-Morrison, J.D., Ghezelayagh, T.S., Lian, S., Zhang, Y., Fredrickson, J., Nachmanson, D., Baker, K.T., Radke, M.R., Hun, E., and Norquist, B.M. (2020). Characterization of TP53 mutations in Pap test DNA of women with and without serous ovarian carcinoma. Gynecologic oncology 156, 407-414. PMID: 31839337
7. Tao, Y*., Kang, B*., Petkovich, D.A., Bhandari, Y.R., In, J., Stein-O'Brien, G., Kong, X., Xie, W., Zachos, N., and Maegawa, S., Brown, S., Chiu, YR., Shao, X., Thakor, J., Lu, Z., Cai, Y., Zhang, Y., Gonzalez, I., Peinado, M., Zahnow, C., Ahuja, N., Fertig, E., Issa, J., Baylin, S*., Easwaran, H*. (2019). Aging-like spontaneous epigenetic silencing facilitates Wnt activation, stemness, and BrafV600E-induced tumorigenesis. Cancer cell 35, 315-328. e316. PMID: 30753828
8. Nachmanson, D., Lian, S., Schmidt, E.K., Hipp, M.J., Baker, K.T., Zhang, Y., Tretiakova, M., Loubet-Senear, K., Kohrn, B.F., and Salk, J.J. (2018). Targeted genome fragmentation with CRISPR/Cas9 enables fast and efficient enrichment of small genomic regions and ultra-accurate sequencing with low DNA input (CRISPR-DS). Genome research 28, 1589-1599. PMID: 30232196
9. Xu, J*., Peng, X*., Chen, Y*., Zhang, Y., Ma, Q., Liang, L., Carter, A.C., Lu, X., and Wu, C.-I. (2017). Free-living human cells reconfigure their chromosomes in the evolution back to uni-cellularity. Elife 6, e28070. PMID: 29251591
10. Deng, L., Zhang, Y., Kang, J., Liu, T., Zhao, H., Gao, Y., Li, C., Pan, H., Tang, X., and Wang, D. (2008). An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism. Human mutation 29, 1209-1216. PMID: 18473345
