巴钊庆博士 - 研究生教育 - 北京生命科学研究所

巴钊庆博士

北京生命科学研究所研究员

Zhaoqing Ba, Ph.D.

Assistant Investigator, NIBS, Beijing

Email: bazhaoqing@nibs.ac.cn

2013年北京生命科学研究所与北京师范大学联合培养生物化学与分子生物学博士
Ph.D. in Biochemistry and Molecular Biology, National Institute of Biological Science (NIBS), Beijing & Beijing Normal University, Beijing, China

2008年江南大学生物工程基地班学士
B.S. in Biotechnology (National Base of Life Science & Biotechnology Education Program), Jiangnan University, Wuxi, Jiangsu, China

2021年- 北京生命科学研究所研究员
Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2019-2021年哈佛医学院/波士顿儿童医院讲师/副研究员
Instructor/Research Associate, Harvard Medical School/Boston Children’s Hospital, Boston, USA

2014-2019 年哈佛医学院/波士顿儿童医院博士后
Postdoctoral Research Fellow, Harvard Medical School/Boston Children’s Hospital, Boston, USA

2013-2014 年清华大学生命科学学院博士后
Postdoctoral Research Fellow, Tsinghua University, Beijing, China

B 淋巴细胞作为适应性免疫系统关键组分之一对机体抵御病原体感染和疾病侵袭至关重要。B 细胞在分化和抗原激活过程中受到精细调控从而在特定时空以“特异性”和“多样性”方式生成抗体,从而使机体能够“适应性”应对纷繁复杂的抗原世界。此外,B 细胞还具有形成高级淋巴结构、重塑T细胞反应、呈递抗原和分泌细胞因子等功能而广泛参与慢性感染、自身免疫、异体移植、组织稳态及肿瘤免疫等过程。B细胞异常导致诸多免疫相关和肿瘤疾病。因此，深入研究B细胞分化和功能调控具有多方面重要意义。然而,囿于B 细胞调控的复杂性和研究手段的局限性,我们对其理解仍不清楚。我们前期通过开发和利用一系列基于高通量测序的新方法系统揭示了小鼠抗体编码基因多样化重排的分子机制,为领域内长期存在的问题提供了新的见解;我们还开发了快速生成 B 淋巴癌小鼠模型的新技术,提供了一种快速生成包括肿瘤免疫研究必需的小鼠疾病模型的通用新方法。未来，我们将继续通过开发和利用新技术在个体、器官组织、细胞、分子多尺度下深入研究 B 细胞分化和功能调控、抗体特异性和多样性塑造机制以及 B 细胞缺陷相关免疫疾病和肿瘤的病理。我们期望通过这些研究最终建立新型高效的疫苗和治疗性抗体的开发平台以及研发能够治疗相关免疫疾病和肿瘤的创新性药物。

As an integral part of adaptive immunity, B lymphocytes play fundamental roles in defensing against infection and illness. During B cell differentiation and antigen activation, extremely diversified antibody repertoires are generated through a highly coordinated spatio-temporal regulation with each B cell expressing a unique antibody, which is pivotal for the immune system to be “adaptable” to the numerous antigens. Moreover, B cells contribute to the establishment of advanced lymphoid structures and are involved in antigen presenting, tissue homeostasis, and immune responses to tumors. B cell dysfunction is associated with various types of diseases including immunodeficiency, autoimmunity, and tumorigenesis. We have devoted major efforts to the development of several innovative high-throughput sequencing-based approaches and addressed the major long-standing enigma of how antibody genes are diversified at the molecular level. We have also developed a rapid mouse model for B-cell lymphomas and provided a new general approach for the generation of genetically complex mouse disease models. In the future, we will continue to develop and employ multidisciplinary state-of-the-art technologies and take multi-scale approaches to further elucidate mechanisms that orchestrate B cell differentiation and function, and antibody diversification, and mechanisms that underlie the related immunological disorders and cancer. Based on the new understanding from the basic research, we will ultimately generate innovative platforms and strategies to develop vaccines and therapeutic antibodies to fight against human diseases.

发表文章 Publications
(*Equal contribution; #Co-correspondence)
Original Articles

1. Liang, Z.*#, Zhao, L.*, Ye, A.Y.*, Lin, S.G.*, Zhang, Y., Guo, C., Dai, H.Q., Ba, Z.#, Alt, F.W.# (2023). Contribution of the IGCR1 regulatory element and the 3'Igh CTCF-binding elements to regulation of Igh V(D)J recombination. Proc. Natl. Acad. Sci. USA 120(26), e2306564120. doi: 10.1073/pnas.2306564120.

2. Ba, Z.*#, Lou, J.*, Ye, A.Y., Dai, H.-Q., Dring, E.W., Lin, S.G., Jain, S., Kyritsis, N., Kieffer-Kwon, K.-R., Casellas, R.#, and Alt, F.W.# (2020). CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning. Nature 586, 305–310.

3. Jain, S.*, Ba, Z.*, Zhang, Y., Dai, H.-Q., and Alt, F.W.# (2018). CTCF-Binding Elements Mediate Accessibility of RAG Substrates During Chromatin Scanning. Cell 174, 102-116. (Recommended as ‘Exceptional’ by Faculty of 1000)

4. Lin, S.G.*, Ba, Z.*, Du, Z.*, Zhang, Y., Hu, J.#, and Alt, F.W.# (2016). Highly Sensitive and Unbiased Approach for Elucidating Antibody Repertoires. Proc. Natl. Acad. Sci. USA 113, 7846-7851. (Recommended by Faculty of 1000)

5. Ba, Z.*, Meng, F.-L.*, Gostissa, M.*, Huang, P.-Y., Ke, Q., Wang, Z., Dao, M.N., Fujiwara, Y., Rajewsky, K., Zhang, B.#, and Alt, F.W.# (2015). A Rapid Embryonic Stem Cell-Based Mouse Model for B-cell Lymphomas Driven by Epstein-Barr Virus Protein LMP1. Cancer Immunol. Res. 3, 641-649.

6. Wei, W.*, Ba, Z.*, Gao, M., Wu, Y., Ma, Y., Amiard, S., White, C.I., Rendtlew Danielsen, J.M., Yang, Y.-G., and Qi, Y.# (2012). A Role for Small RNAs in DNA Double-Strand Break Repair. Cell 149, 101-112. (Selected as Best of Cell in 2012, also featured and highlighted in Nat. Rev. Mol. Cell Biol., 2012, Nat. Rev. Gen., 2012, Nat. Struct. & Mol. Biol., 2012, and Faculty of 1000)

7. Dai, H.-Q.*#, Hu, H.*, Lou, J., Ye, A.Y., Ba, Z., Zhang, X., Zhang, Y., Zhao, L., Yoon, H.S., Chapdelaine-Williams, A.M., Kyritsis, N., Chen, H., Johnson, K., Lin, S., Conte, A., Casellas, R., Lee, C.-S.# and Alt, F.W.# (2021). Loop extrusion mediates physiological Igh locus contraction for RAG scanning. Nature 590, 338–343.

8. Chen, H.*, Zhang, Y.*, Ye, A.Y.*, Du, Z., Xu, M., Lee, C.-S., Hwang, J.K., Kyritsis, N., Ba, Z., Neuberg, D., Littman, D.R., and Alt, F.W.# (2020). BCR selection and affinity maturation in Peyer’s patch germinal centres. Nature 582, 421-425.

9. Zhang, X., Zhang, Y., Ba, Z., Kyritsis, N., Casellas, R., and Alt, F.W.# (2019). Fundamental roles of chromatin loop extrusion in antibody class switching. Nature 575, 385-389.

10. Zhang, Y.*, Zhang, X.*, Ba, Z., Liang, Z., Dring, E.W., Hu, H., Lou, J., Kyritsis, N., Zurita, J., Shamim, M.S., Presser Aiden, A., Lieberman Aiden E., and Alt, F.W.# (2019). The fundamental role of chromatin loop extrusion in physiological V(D)J recombination. Nature 573, 600-604.

11. Liu, M., Ba, Z., Costa-Nunes, P., Wei, W., Li, L., Kong, F., Li, Y., Chai, J., Pontes, O., and Qi, Y.# (2017). IDN2 Interacts with RPA and Facilitates DNA Double-Strand Break Repair by Homologous Recombination in Arabidopsis. Plant Cell 29, 589-599.

12. Gao, M.*, Wei, W.*, Li, M.-M.*, Wu, Y.-S.*, Ba, Z., Jin, K.-X., Li, M.-M., Liao, Y.-Q., Adhikari, S., Chong, Z., et al. (2014). Ago2 Facilitates Rad51 Recruitment and DNA Double-Strand Break Repair by Homologous Recombination. Cell Research 24, 532-541. (Featured by “Research Highlight”)

Invited Review and Book Chapter

1. Lin, S.G.*, Ba, Z.*, Alt, F.W.#, and Zhang, Y. (2018). RAG Chromatin Scanning During V(D)J Recombination and Chromatin Loop Extrusion Are Related Processes. Adv. Immunol. 139, 93-135.

2. Ba, Z., and Qi, Y.# (2013). Small RNAs: Emerging Key Players in DNA Double-Strand Break Repair. Science China Life Sciences 56, 933-936.

专利 Patents

1. Alt, F.W., Jain, S., Ba, Z., Tian, M. Methods and compositions relating to high-throughput models for antibody discovery and/or optimization. PCT/US2019/036321. Application filed 2019-06-10.

2. Alt, F.W., Meng, F.-L., Ba, Z., Gostissa, M., Zhang, B., Wei, P.-C., Schwer, B. Methods and compositions relating to an embryonic stem cell-based tumor model. US15/564,647. Application filed 2016-04-07.