Dr. Zhao is a Professor of Cell Biology at Kunming Institute of Zoology (KIZ), Chinese Academy of Sciences. Zhao received Ph.D. degree from KIZ in 2013. After postdoctoral training at the Wistar Institute in Philadelphia, Zhao re-joined in KIZ as a faculty member in 2020. He also serves as executive director of Biological and Toxicity platform, National Primate Research Facility for Phenotypic & Genetic Analysis of Model Animals. Zhao’s Lab studies genome-environment interactions and human health, with interests covering hypoxia, ambient ultrafine particles and organ developmental toxicity. His works have been published in journals including Cell Stem Cell, Cell Research, Science Advances and Nature Communications. His group is being supported by funding from Ministry of Science and Technology of China, Chinese Academy of Sciences and Yunnan province.

2020.09  Present   Principal Investigator, PhD Supervisor, Kunming Institute of Zoology, CAS

2017.06 – 2020.07   Postdoctoral Fellow, Wistar Institute, Philadelphia, USA

2016.01 – 2017.05   Associate Researcher, Kunming Institute of Zoology, CAS

2013.08 – 2015.12   Assistant Researcher, Kunming Institute of Zoology, CAS

2007.09 – 2013.07   PhD in Science, Kunming Institute of Zoology, CAS

2003.09 – 2007.06   Bachelor's in Science, School of Life Sciences, Yantai University

1. Stem Cell and Organoid Technologies

Pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have the abilities of both self-renewal and multi-lineage differentiation. Organoids, constructed from pluripotent stem cells through 3D culture and directed differentiation, can efficiently simulate the developmental process, physiological characteristics, cell composition, and gene expression of human organs. As a result, organoid technology has become a cutting-edge technique in stem cell biology and tissue engineering research fields, with significant values in biomedical research and applications such as drug screening and toxicological evaluation. We have developed organoid culture systems using human pluripotent stem cells to generate heart organoids, microvascular organoids, and brain organoids (mini-brain). Integrating microfluidic chip technics, we are achieving large-scale production, high-throughput continuous dynamic monitoring, and phenotypic evaluation using these types of organoids. We aim to build a comprehensive organoid research platform to support relevant R&D needs.

2. Effects of Environmental Pollutants on human Cardiovascular, Brain, and Reproduction

Human health is being crosslinked to both genetic and environmental factors. Since the Industrial Revolution, human health has been threatened by increasing environmental pollutants. Indeed, study of pollution toxicity has become a major topic of Exposome research. Some key questions need to be addressed including how to cope with diversifying pollutants, especially persistent and emerging pollutants, how to mitigate their detrimental effects on human health meanwhile balancing industrial development with environmental protection. This needs interdisciplinary knowledge across fields such as biomedical sciences, environmental science, and material science. It is known that pollutants pose particular risks to pregnant women, infants, and the elderly, significantly contributing to the high incidence of cardia-cerebrovascular diseases and reproductive genetic toxicity. However, the molecular toxicological mechanisms remain unclear. In terms of government environmental management, the absence of basic research data makes it difficult to set environmental baselines and safe emission standards. We utilize cardia- cerebrovascular organoid platforms and in vivo animal models including mice and non-human primates to investigate the effects of typical solid ultrafine particulate pollutants (e.g., nanoplastics, carbon black nanoparticles, nanosilica, etc.) and emerging pollutants on cardia-cerebrovascular development and homeostasis, as well as on reproductive genetics (e.g., bio-corona adsorption of pollutants onto biomolecules; disturbance to gene expression, cell lineage, organ development, and function; impact on genomic stability; pollutant-driven genomic mutations, etc.). Our goal is to better understand the molecular toxicological effects of pollutants, develop health protection strategies, and support to official environmental management.

3. Effects of Hypoxia on Organ Development and Function

Oxygen is crucial for life processes. Hypoxia (insufficient oxygen supply) is another significant environmental stressor. Hypoxia may disrupt gene expression pattern, impair genomic stabilization, reshapes cell homeostasis and the tissue microenvironment. Hypoxia associates with many major human diseases such as cardia-cerebrovascular diseases and solid tumors. We utilize cardia-cerebrovascular organoids and solid tumor (pancreatic cancer) organoids models to investigate hypoxia-driven gene expression and cellular remodeling, genomic stability (DNA replication, DNA repair), and mutation patterns. Our aim is to elucidate the acute and chronic effects of hypoxia on human physiology and pathology, and to develop new strategies to effectively cope with hypoxic stress.

Youth Editorial Board Member of Zoological Research, The Innovation, Genome Instability & Disease journals

2016: Member of the Youth Innovation Promotion Association, Chinese Academy of Sciences

2016: Travel Award, International Stem Cell Society (ISSCR) Annual Meeting, San Francisco, USA

2015: Travel Award, International Stem Cell Society (ISSCR) Annual Meeting, Stockholm, Sweden

2015: Excellent Thesis Award, Yunnan Provincial Association of Research Institutions

Papers published as corresponding/co-corresponding author:

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

Papers published as first/co-first author:

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.

Papers published as co-author:

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