1. 干细胞和类器官技术

多能干细胞（胚胎干细胞或诱导性多能干细胞）具有无限增殖和多潜能分化的特性。以多能干细胞为初始材料经过立体培养和定向分化构建而成的类器官，能够高效模拟人体器官的发育进程、生理特征、细胞组成、基因表达等。因此，类器官技术已成为干细胞生物学和组织工程领域的前沿技术，在生物医学基础研究和药物筛选、毒理评价等应用研究中具有重要价值。我们利用人源多能干细胞开发了心脏类器官、微血管类器官、脑类器官（类脑）等构建培养体系，结合微流控芯片技术实现心脑血管类器官的规模化制备、高通量连续动态监测和表型评价，旨在打造类器官研究综合平台，支撑相关的研发需求。

2. 环境污染物对心脑血管和生殖遗传的损害效应

人体健康受到遗传和环境因素的交互影响。自工业革命以来，环境污染物与日俱增、层出不穷，已成为环境胁迫暴露组学研究的重要内容。如何有效应对海量的污染物，特别是持久性污染物和新污染物对人体健康的损害效应，平衡产业发展和环境保护，是当前生物医学、环境科学、材料科学等学科交叉研究的重点。已知污染物尤其危害妊娠期、婴幼儿和老年群体，并显著造成心脑血管疾病高发和生殖遗传毒性，但分子毒理机制不明，更缺乏针对性的健康保护策略。在政府环保管控方面，由于基础研究数据的缺乏，尚难以设定环保基线和安全排放标准。我们利用心脑血管类器官平台和小鼠、非人灵长类等活体动物模型，着重研究单一或复合的固体超细颗粒污染物（纳米塑料、炭黑颗粒、纳米硅等）和新污染物对心脑血管发育和稳态的影响，以及对生殖遗传的分子毒理机制（例如污染物对生物分子的吸附；污染物对基因表达、细胞谱系、器官发育和功能的扰动效应；污染物对基因组稳定性维持能力的影响；污染物驱动的基因组变异特征和规律等），以期深刻认识污染物的分子毒理效应，研发健康保护策略，支撑环保管控标准的制定。

3. 低氧对器官发育和功能的影响

氧分子对于生命活动至关重要。低氧（氧供应不足）是环境胁迫的另一个重要方面。低氧扰动基因表达模式，削弱基因组稳定性维持能力，重塑细胞稳态和组织微环境，关联心脑血管疾病和实体瘤等人类重大疾病。我们利用心脑血管类器官和实体瘤（胰腺癌）类器官模型，着重研究低氧驱动的基因表达和细胞重塑、基因组稳定性（DNA复制、DNA修复）和变异规律等，旨在解析急性或慢性低氧对人体生理或病理的影响，研发有效应对低氧胁迫的新策略。

1. 科技部重点研发计划“发育编程及其代谢调节”项目子课题，主持

2. 科技部重点研发计划“常见多发病防治”项目子课题，骨干

3. 中国科学院人才支持项目，主持

4. 云南省基础研究重点项目，主持

5. 云南省兴滇人才项目，主持

6. 昆明市“春城创新团队”项目

7. 昆明医科大学联合专项，合作

Zoological Research, The Innovation, Genome Instability & Disease期刊青年编委

2016年：中国科学院青年创新促进会会员

2016年：国际干细胞学会（ISSCR）年会旅行奖，美国旧金山

2015年：国际干细胞学会（ISSCR）年会旅行奖，瑞典斯德哥尔摩

2015年：云南省科研机构联合会，年度优秀论文奖

以通讯/共同通讯作者身份发表论文:

1. Qiu Tu^#, Xiuyun Liu^#, Xiaoqing Yao^#, Ruixue Li^#, Gaojing Liu^#, Honglv Jiang, Kaiqin Li, Qiongfang Chen, Xiaoyan Huang, Qing Chang, Guoqiang Xu*, Hong Zhu*, Peng Shi*, Bo Zhao*. RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma. Journal of Experimental & Clinical Cancer Research. Sep 15;41(1):274. 2022.

2. Weidao Zhang^#, Min Tang^#, Lin Wang, Hu Zhou, Jing Gao, Zhongliang Chen, Bo Zhao*, Ping Zheng*. Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis. Science Advances. Jan 27;9(4):eadf6277. 2023.

3. Kaiqin Li^#, Gaojing Liu^#, Xiuyun Liu^#, Qiongfang Chen^#, Xiaoyan Huang^#, Qiu Tu, Jiao Zhang, Qing Chang, Yunhua Xie, Rong Hua, Dongming Xu, Zhen Liu, Bo Zhao*. EPAS1 prevents telomeric damage induced senescence through enhancing transcription of TRF1, TRF2 and RAD50. Zoological Research, May 18;44(3):636-649. 2023

4. Weidao Zhang, Min Tang, Lin Wang, Ping Zheng*, Bo Zhao*. Purification of Long Non-coding RNAs on Replication Forks Using iROND (Isolate RNAs on Nascent DNA). Bio Protocol, Nov 5;13(21):e4869. 2023

5. Wanzhi Cai^#, Xiaoqing Yao^#, Gaojing Liu, Xiuyun Liu, Bo Zhao*, Peng Shi*. RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells. Cellular and Molecular Life Sciences, Aug 22;81(1):366. 2024

6. Qiu Tu, Gaojing Liu, Xiuyun Liu, Jiao Zhang, Wenxian Xiao, Longbao Lv*, Bo Zhao*. Perspective on using non-human primates in Exposome research. Ecotoxicology and Environmental Safety. Nov 1:286:117199. 2024

以第一/共同第一作者身份发表论文:

1. Bo Zhao, Wei-dao Zhang, Ying-liang Duan, Yong-qing Lu, Yi-xian Cun, Chao-hui Li, Kun Guo, Wen-hui Nie, Lei Li, Rugang Zhang, Ping Zheng*. Filia is an ESC-specific regulator of DNA damage response and safeguards genomic stability. Cell Stem Cell, 16: 684-98. 2015.

2. Bo Zhao^#, Weidao Zhang^#, Yixian Cun, Jingzheng Li, Yan Liu, Jing Gao, Hongwen Zhu, Hu Zhou, Rugang Zhang, Ping Zheng*. Mouse embryonic stem cells have increased capacity for replication fork restart driven by the specific Filia-Floped protein complex. Cell Research, 28: 69-89. 2018.

3. Bo Zhao, Jianhuang Lin, Lijie Rong, Shuai Wu, Zhong Deng, Nail Fatkhutdinov, Joseph Zundell, Takeshi Fukumoto, Qin Liu, Andrew Kossenkov, Stephanie Jean, Mark G. Cadungog, Mark E. Borowsky, Ronny Drapkin, Paul M. Lieberman, Cory T. Abate-Shen, Rugang Zhang*. ARID1A promotes genomic stability through protecting telomere cohesion. Nature Communications. Sep 6;10(1):4067. 2019.

4. Bo Zhao, Pingyu Liu, Takeshi Fukumoto, Timothy Nacarelli, Nail Fatkhutdinov, Shuai Wu, Jianhuang Lin, Katherine M. Aird, Hsin-Yao Tang, Qin Liu, David W. Speicher, Rugang Zhang*. Topoisomerase 1 cleavage complex enables pattern recognition and inflammation during senescence. Nature Communications. Feb 19;11(1):908. 2020.

5. Xue Hao^#; Bo Zhao^#; Wei Zhou; Heng Liu; Takeshi Fukumoto; Dmitry Gabrilovich; Rugang Zhang*; Sensitization of ovarian tumor to immune checkpoint blockade by boosting senescence-associated secretory phenotype. iScience. 24(1): 102016. 2021.

6. Huan Liu^#, Bo Zhao^#, Yongchang Chen^#, Dewen You, Rui Liu, Mingqiang Rong, Weizhi Ji*, Ping Zheng, Ren Lai*. Multiple coagulation factor deficiency protein 2 contains the ability to support stem cell self-renewal. FASEB J. 27: 3298-305, 2013.

7. Bo Zhao, Yi-Xian Cun, Xie-Chao He，Ping Zheng*. Maternal-effect Floped gene is essential for the derivation of embryonic stem cells in mice. Zoological Research, 34: E82-6. 2013.

以合作者身份发表论文:

1. Sergey Karakashev^#, Hengrui Zhu^#, Yuhki Yokoyama^#, Bo Zhao, Nail Fatkhutdinov, Andrew V. Kossenkov, Andrew J. Wilson, Fiona Simpkins, David Speicher, Dineo Khabele, Benjamin G. Bitler, Rugang Zhang*. BET bromodomain inhibition synergizes with PARP inhibitor in epithelial ovarian cancer. Cell Reports, 21: 3398-3405, 2017.

2. Huaixiao Ma^#, Jinglei Zha^#, Haifeng Wan^#, Xiangxiang Jiang^#, Xiaoxiao Wang, Lin Wang, Yunlong Xiang, Xiechao He, Zhen-Ao Zhao, Bo Zhao, Ping Zheng*, Lei Li*, Hongmei Wang*. In vitro culture of cynomolgus monkey embryos beyond early gastrulation. Science. Oct 31. pii: eaax7890. 2019.

3. Weidao Zhang^#, Zhongliang Chen^#, Dengfeng Zhang, Bo Zhao, Lu Liu, Zhengyuan Xie, Yonggang Yao, Ping Zheng*. KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells. PLOS Biology, Oct 14;17(10):e3000468. 2019.

4. Sergey Karakashev, Takeshi Fukumoto, Bo Zhao, Jianhuang Lin, Shuai Wu, Nail Fatkhutdinov, Pyoung-Hwa Park, Galina Semenova, Stephanie Jean, Mark G. Cadungog, Mark E. Borowsky, Andrew V. Kossenkov, Qin Liu, Rugang Zhang*. EZH2 Inhibition Sensitizes CARM1-High, Homologous Recombination Proficient Ovarian Cancers to PARP Inhibition. Cancer Cell. 37, 1–11, February 10, 2020.

5. Jingzheng Li^#, Yafang Shang, Lin Wang, Bo Zhao, Chunli Sun, Jiali Li, Siling Liu, Cong Li, Min Tang, Fei-Long Meng*, Ping Zheng*. Genome integrity and neurogenesis of postnatal hippocampal neural stem/progenitor cells require a unique regulator Filia. Science Advances, 2020, 6(44): eaba0682.

6. Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Edgar Luzete Monteiro, Xin Xu, Christina Freeman, Hongzhuang Peng, Hsin-Yao Tang, Aaron Havas, Andrew V Kossenkov, Shelley L Berger, Peter D Adams, David W Speicher, David Schultz, Ronen Marmorstein, Kenneth S Zaret, Rugang Zhang. TXNRD1 drives the innate immune response in senescent cells with implications for age-associated inflammation. Nature Aging. Feb;4(2):185-197. 2024