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石磊  研究员
神经基因组学学科组
职  务: 神经基因组学学科组负责人
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电子邮件: shilei@mail.kiz.ac.cn
通讯地址: 云南省昆明市盘龙区龙欣路17号 中国科学院昆明动物研究所    650201
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  简  历

石磊,博士。2007年毕业于西南大学获理学学士学位。2012年在中国科学院昆明动物研究所获遗传学博士学位(主要从事灵长类大脑进化研究,首次建立大脑进化相关基因的转基因猕猴模型)。2013年在美国北卡罗莱纳大学教堂山分校学习猕猴大脑MRI影像数据处理。2015-2019年在美国密歇根大学神经科学研究所,以小鼠为模型,开展大脑皮层发育方面的研究(阐明神经元细胞基因组损伤对大脑及动物个体适应度影响的分子细胞机制),2019-2021年在美国Salk生物研究所,从事衰老与再生方向的研究。2021年10月引进回昆明动物研究所,成立神经基因组学课题组。主要从事灵长类大脑进化发育与衰老方向的研究。

 

学习和研究经历

2020.10-至今    研究员, 博士生导师,中国科学院昆明动物研究所神经基因组学学科组负责人

2019.03-2020.10 美国Salk生物研究所, 博士后 (Postdoctoral Fellow, Salk Institute for Biological Studies, La Jolla,导师: Juan Carlos Izpisua Belmonte)

2015.07-2019.03 美国密歇根大学安娜堡分校, 博士后 (Postdoctoral Research Fellow, University of Michigan, Ann Arbor,导师: Kenneth Y. Kwan)

2012.07-2015.07 中国科学院昆明动物研究所, 助理研究员

2013.01-2013.07 美国北卡罗莱纳大学教堂山分校, 访问学者 (Visiting Scholar, University of North Carolina, Chapel Hill)

2007.09-2012.07 中国科学院昆明动物研究所, 遗传学 理学博士(导师: 宿兵)

2003.09-2007.07 西南大学生命科学学院, 生物技术 理学学士

 

  研究方向

为了理解人类高级认知功能的由来,我们必须理解其重要的生物学基础-大脑皮层。大脑皮层是哺乳动物神经系统进化出来的高度复杂的结构,调控人类的感觉,运动,认知,语言等功能。近年来3D类脑器官培养,多组学测序技术以及基因编辑技术的不断进步,使得我们对神经科学的研究处于一个快速发展的时期。基于此,课题组依托中国科学院昆明动物研究所相关平台包括大型仪器中心、灵长类大设施等,利用经典模式动物小鼠和西南地区丰富的灵长类实验动物资源,结合神经发育生物学、遗传学、进化生物学及相关功能基因组学的实验技术手段,深入系统地开展多物种同源脑区及其形成的分子遗传基础的比较研究,旨在回答人类智力起源及演变的前沿科学问题。聚焦在四个主要的方面:

(1)灵长类进化过程中,人类大脑容量扩增以及沟回演变的分子遗传基础和细胞基础是什么?

(2)哺乳动物大脑发育过程中,神经前体细胞命运分化决定的分子细胞机制是什么?

(3)人类智力障碍疾病的致病基因在大脑发育中的作用机制是什么?

(4)人类大脑衰老过程中,哪些基因表达水平以及哪些细胞类型和数目的变化导致大脑认知功能下降的?

  承担科研项目

1.国家自然科学基金面上项目: 人类特异性DNA甲基化区域在灵长类大脑进化中的功能研究,2022.01-2025.12,58万元,主持

2.国家自然科学基金青年项目:人类大脑进化关键基因MCPH1调控和功能研究, 2014.01-2016.12, 23万元, 已结题;

3.中国科学院西部之光博士项目:小头症基因MCPH1的进化和功能研究, 2012-2014, 20万元, 已结题;

  专家类别
研究员
  社会任职
  获奖及荣誉
  代表论著

1.      Browder, K. C., Reddy, P., Yamamoto, M., Haghani, A., Guillen, I. G., Sahu, S., Wang, C., Luque, Y., Prieto, J., Shi, L., Shojima, K., Hishida, T., Lai, Z., Li, Q., Choudhury, F. K., Wong, W. R., Liang, Y., Sangaraju, D., Sandoval, W., Esteban, C. R., Delicado, E. N., Garcia, P. G., Pawlak, M., Vander Heiden, J. A., Horvath, S., Jasper, H. & Izpisua Belmonte, J. C. (2022). In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice. Nature Aging.2, 243-253.

2.      Liu, H., Li, R., Liao, H.-K., Min, Z., Wang, C., Yu, Y., Shi, L., Dan, J., Hayek, A., Martinez Martinez, L., Nu?ez Delicado, E. & Izpisua Belmonte, J. C. (2021) Chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells. Nature Communications. 12, 3330.

3.      Wang, C., Rabadan Ros, R., Martinez-Redondo, P., Ma, Z., Shi, L., Xue, Y., Guillen-Guillen, I., Huang, L., Hishida, T., Liao, H.-K., Nunez Delicado, E., Rodriguez Esteban, C., Guillen-Garcia, P., Reddy, P. & Izpisua Belmonte, J. C. (2021) In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. Nature Communications 12, 3094.

4.      Keil, J.M., Doyle, D.Z., Qalieh, A., Lam, M.M., Funk, O.H., Qalieh, Y., Shi, L., Mohan, N., Sorel, A., and Kwan, K.Y. (2020). Symmetric neural progenitor divisions require chromatin-mediated homologous recombination DNA repair by Ino80. Nature Communications 11, 3839.

5.      Li, R., Zhong, C., Yu, Y., Liu, H., Sakurai, M., Yu, L., Min, Z., Shi, L., Wei, Y., Takahashi, Y., Liao, H. K., Qiao, J., Deng, H., Nunez-Delicado, E., Rodriguez Esteban, C., Wu, J. and Izpisua Belmonte, J. C. (2019). Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures. Cell 179 (3), 687-702.

6.      Shi, L., Qalieh, A., Lam, M. M., Keil, J. M., and Kwan, K. Y. (2019). Robust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Knl1 deletion. Nature Communications 10 (1):2588

7.      Shi, L., and Su, B. (2019). A transgenic monkey model for the study of human brain evolution. Zoological Research 40 (3):236-38

8.      Shi, L#., Luo, X#., Jiang, J#., Chen, Y#., Liu, C#., Hu, T., Li, M., Lin, Q., Li, Y., Huang, J., Wang, H., Niu, Y., Shi, Y., Styner, M., Wang, J., Lu, Y., Sun, X., Yu, H., Ji, W., and Su, B. (2019). Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development. National Science Review 6 (3):480-93

9.      Shi, L#., Hu, E. Z#., Wang, Z. B#., Liu, J. W., Li, J., Li, M., Chen, H., Yu, C. S., Jiang, T. Z., and Su, B. (2017). Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution. Human Genetics 136 (2):193-204

10. #Mendizabal, I., #Shi, L., Keller, T. E., Konopka, G., Preuss, T. M., Hsieh, T. F., Hu, E. Z., Zhang, Z., Su, B., and Yi, S. V. (2016). Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution. Molecular Biology and Evolution 33 (11):2947-59

11. Shi, L#., Zhang, Z#., and Su, B. (2016). Sex Biased Gene Expression Profiling of Human Brains at Major Developmental Stages. Scientific Reports 6

12. Shi, L., Lin, Q., and Su, B. (2015). Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates. BMC Evol Biol 15:127

13. Shi, L#., Lin, Q#., and Su, B. (2014). Human-Specific Hypomethylation of CENPJ, a Key Brain Size Regulator. Molecular Biology and Evolution 31 (3):594-604

14. Li, M., Luo, X. J., Rietschel, M., Lewis, C. M., Mattheisen, M., Muller-Myhsok, B., Jamain, S., Leboyer, M., Landen, M., Thompson, P. M., Cichon, S., Nothen, M. M., Schulze, T. G., Sullivan, P. F., Bergen, S. E., Donohoe, G., Morris, D. W., Hargreaves, A., Gill, M., Corvin, A., Hultman, C., Toga, A. W., Shi, L., Lin, Q., Shi, H., Gan, L., Meyer-Lindenberg, A., Czamara, D., Henry, C., Etain, B., Bis, J. C., Ikram, M. A., Fornage, M., Debette, S., Launer, L. J., Seshadri, S., Erk, S., Walter, H., Heinz, A., Bellivier, F., Stein, J. L., Medland, S. E., Arias Vasquez, A., Hibar, D. P., Franke, B., Martin, N. G., Wright, M. J., Moo, D. S. B. C., Swedish Bipolar Study, G., Alzheimer's Disease Neuroimaging, I., Consortium, E., Consortium, C. & Su, B. (2014). Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. Molecular Psychiatry 19 (4):452-61

15. Shi, L., Li, M., Lin, Q., Qi, X. B., and Su, B. (2013). Functional divergence of the brain-size regulating gene MCPH1 during primate evolution and the origin of humans. BMC Biology 11

16. Li, M., Luo, X. J., Xiao, X., Shi, L., Liu, X. Y., Yin, L. D., Ma, X. Y., Yang, S. Y., Pu, X. F., Yu, J., Diao, H. B., Shi, H., and Su, B. (2013). Analysis of common genetic variants identifies RELN as a risk gene for schizophrenia in Chinese population. World Journal of Biological Psychiatry 14 (2):91-99

17. Shi, L., and Su, B. (2012). Identification and functional characterization of a primate-specific E2F1 binding motif regulating MCPH1 expression. FEBS Journal 279 (3):491-503

18. Shi, L., Li, M., and Su, B. (2012). MCPH1/BRIT1 represses transcription of the human telomerase reverse transcriptase gene. Gene 495 (1):1-9

19. Li, M., Luo, X. J., Xiao, X., Shi, L., Liu, X. Y., Yin, L. D., Diao, H. B., and Su, B. (2011). Allelic Differences Between Han Chinese and Europeans for Functional Variants in ZNF804A and Their Association with Schizophrenia. American Journal of Psychiatry 168 (12):1318-25

20. Li, M., Mo, Y., Luo, X. J., Xiao, X., Shi, L., Peng, Y. M., Qi, X. B., Liu, X. Y., Yin, L. D., Diao, H. B., and Su, B. (2011). Genetic association and identification of a functional SNP at GSK3 beta for schizophrenia susceptibility. Schizophrenia Research 133 (1-3):165-71

21. Niu, Y. Y., Yu, Y., Bernat, A., Yang, S. H., He, X. C., Guo, X. Y., Chen, D. L., Chen, Y. C., Ji, S. H., Si, W., Lv, Y. Q., Tan, T., Wei, Q. A., Wang, H., Shi, L., Guan, J. A., Zhu, X. M., Afanassieff, M., Savatier, P., Zhang, K., Zhou, Q., and Ji, W. Z. (2010). Transgenic rhesus monkeys produced by gene transfer into early-cleavage-stage embryos using a simian immunodeficiency virus-based vector. PNAS 107 (41):17663-67

 

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