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巴釗慶博士

北京生命科學研究所研究員

Zhaoqing Ba, Ph.D.

Assistant Investigator, NIBS, Beijing

Email: bazhaoqing@nibs.ac.cn

2013年? ?北京生命科學研究所與北京師范大學聯合培養生物化學與分子生物學博士
Ph.D. in Biochemistry and Molecular Biology, National Institute of Biological Science (NIBS), Beijing & Beijing Normal University, Beijing, China

2008年? ?江南大學生物工程基地班學士
B.S. in Biotechnology (National Base of Life Science & Biotechnology Education Program), Jiangnan University, Wuxi, Jiangsu, China

2021年-? ?北京生命科學研究所研究員
Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2019-2021年? ? 哈佛醫學院/波士頓兒童醫院講師/副研究員
Instructor/Research Associate, Harvard Medical School/Boston Children’s Hospital, Boston, USA

2014-2019 年? ? 哈佛醫學院/波士頓兒童醫院博士后
Postdoctoral Research Fellow, Harvard Medical School/Boston Children’s Hospital, Boston, USA

2013-2014 年? ? ?清華大學生命科學學院博士后
Postdoctoral Research Fellow, Tsinghua University, Beijing, China

B 淋巴細胞作為適應性免疫系統關鍵組分之一對機體抵御病原體感染和疾病侵襲至關重要。B 細胞在分化和抗原激活過程中受到精細調控從而在特定時空以“特異性”和“多樣性”方式生成抗體,從而使機體能夠“適應性”應對紛繁復雜的抗原世界。此外,B 細胞還具有形成高級淋巴結構、重塑T細胞反應、呈遞抗原和分泌細胞因子等功能而廣泛參與慢性感染、自身免疫、異體移植、組織穩態及腫瘤免疫等過程。B細胞異常導致諸多免疫相關和腫瘤疾病。因此，深入研究B細胞分化和功能調控具有多方面重要意義。然而,囿于B 細胞調控的復雜性和研究手段的局限性,我們對其理解仍不清楚。我們前期通過開發和利用一系列基于高通量測序的新方法系統揭示了小鼠抗體編碼基因多樣化重排的分子機制,為領域內長期存在的問題提供了新的見解;我們還開發了快速生成 B 淋巴癌小鼠模型的新技術,提供了一種快速生成包括腫瘤免疫研究必需的小鼠疾病模型的通用新方法。未來，我們將繼續通過開發和利用新技術在個體、器官組織、細胞、分子多尺度下深入研究 B 細胞分化和功能調控、抗體特異性和多樣性塑造機制以及 B 細胞缺陷相關免疫疾病和腫瘤的病理。我們期望通過這些研究最終建立新型高效的疫苗和治療性抗體的開發平臺以及研發能夠治療相關免疫疾病和腫瘤的創新性藥物。

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.

發表文章 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.

專利 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.

研究生教育

巴釗慶博士