云顶集团(中国)

王伟 博士

北京科学生命云顶集团(中国)研究员

Wei Wang, Ph.D.

Assistant Investigator,  NIBS, Beijing，China

Email: wangwei@wanzixs.com

Home page: http://killifishlab.com/

Ph.D. in Biology, The University of Alabama, USA

M.S. in Genetics, Northwest A&F University, Yangling, China

2021-Present 北京科学生命云顶集团(中国)研究员

Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2014-2021年 美国斯托瓦斯医学云顶集团(中国)、霍华德·休斯医学云顶集团(中国)博士后

器官原位再生在帮助人类恢复因损伤、疾病、衰老等造成的器官功能减弱或丧失方面具有巨大潜力，是生物医学领域亟待解决的重大科学问题。在自然界中，部分低等脊椎生物（例如鱼类、蝾螈等）具有极强的器官再生能力，他们可以完美地修复受损的心脏、大脑、脊髓及肢体；相比之下，哺乳动物（包括人类）却丧失了这些能力。决定不同器官再生或不能再生的分子机制、以及如何让哺乳动物重新取得器官再生能力仍是领域内未解的难题。以哺乳动物耳廓损伤为研究模型，我们率先发现了决定器官再生能力的“分子开关”的存在，关闭“开关”会导致再生物种丧失再生能力，而重启“开关”可以激活不可再生器官的再生能力 。这一发现为解析哺乳动物脊髓等其他核心器官再生失败的分子机制给予了新思路。借助具有显著优势的短寿非洲鳉鱼（Nothobranchius furzeri）模型及具有强大遗传学工具的小鼠模型，王伟实验室的主要研究兴趣是鉴定赋予器官再生能力的核心分子机制，并以其为靶标顺利获得再生医学手段探索人类受损器官的重建。

非洲鳉鱼栖息在非洲东南部遭受季节性干旱的临时水塘中。成年的非洲鳉鱼仅在雨季池塘蓄水时才会出现。在干旱无水的季节，非洲鳉鱼以被埋在泥中且处于滞育（diapause）或休眠状态的胚胎形式存活，等待下一个雨季孵化并再次繁殖。强大的自然选择压力使得该物种进化出了独有的特征，这些特征可以大大加速器官发育、再生及衰老相关的研究：1）生长及性成熟速度快（野外14天即可性成熟，实验室条件下30-45天可性成熟），极大地节省了遗传操作和实验时间； 2）在实验室内胚胎可以进入滞育或休眠长达5-6年，使得遗传品系的长期保存方便且费用低，无需像其他动物模型需要长期饲养成年动物； 3）在实验室条件下衰老速度极快（平均寿命为3-5个月），是现在实验室可饲养的寿命最短的脊椎动物模型； 4）拥有高效的遗传操作技术：CRISPR/Cas9基因敲除及敲入、Tol2介导的转基因等。总之，非洲鳉鱼为成年动物器官发育、再生和衰老研究带来了传统模型所缺乏的显著优势和全新机遇。

Regeneration has long attracted biomedical interest because of the potential of replacing damaged organs with new ones. However, why some lower vertebrates (e.g., fish and salamanders) regenerate extensively while others such as mammals regenerate poorly is not well understood. In addition to the popular mouse model, the Wang lab is also powered with a new genetic model, the African killifish Nothobranchius furzeri. We are deploying comparative studies and genetic screens to decode the failure of regeneration in non-regenerative animals. The Wang Lab is interested in identifying molecular mechanisms that can be targeted to help humans rebuild damaged organs. Our current research will focus on, but not be limited to, the following areas:

(1) The molecular basis of spinal cord regeneration.

(2) Evolution of regenerative capacities in vertebrates.

(3) Regeneration and Rejuvenation.

Wang Lab website: http://killifishlab.com/

Representative Research Articles:

1. Lin, W., Jia, X., Shi, X., He, Q., Zhang, P., Zhang, X., Zhang, L., Wu, M., Ren, T., Liu, Y., Deng, H., Li, Y., Liu, S., Huang, S., Kang, J., Luo, J.#, Deng, Z.#, Wang, W.#, 2025. Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch. Science 388, eadp0176. 10.1126/science.adp0176.

2. Zhang, JQ., Zhou YQ., Yue, W., Zhu ZS., Wu XL., Yu, S., Shen QY., Pan Q., Xu, WJ., Zhang, R., Wu, XJ., Li, XM., Li, YY, Li, YX., Wang, Y., Peng, S., Zhang, SQ., Lei, AM., Ding, XB., Yang, F., Chen, XQ., Li, N.#, Liao, MZ.#, Wang, W. #, Hua, JL#, 2022. Super-enhancers conserved within placental mammals maintain stem 云顶集团(中国) pluripotency, Proc Natl Acad Sci U S A, 119 (40) e2204716119.

3. Wang, W., Hu, C.-K., Zeng, A., Alegre, D., Hu, D., Gotting, K., Ortega Granillo, A., Wang, Y., Robb, S., Schnittker, R., Zhang, S., Alegre, D., Li, H., Ross, E., Zhang, N., Brunet, A., Sánchez Alvarado, A., 2020. Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates. Science 369, (10.1126/science.aaz3090).

Research Highlights in Nature: Why some animals have the power of regeneration. http://www.nature.com/articles/d41586-020-02529-5

Research Highlights in Nature Reviews Genetics: Enhancing regeneration.

http://www.nature.com/articles/s41576-020-00290-z

4. Hu, C.K., Wang, W., Brind'Amour, J., Singh, P.P., Reeves, G.A., Lorincz, M.C., Alvarado, A.S., Brunet, A., 2020. Vertebrate diapause preserves organisms long term through Polycomb complex members. Science 367, 870-874.

5. Cao, C., Lemaire, L.A., Wang, W., Yoon, P.H., Choi, Y.A., Parsons, L.R., Matese, J.C., Wang, W., Levine, M., Chen, K., 2019. Comprehensive single-云顶集团(中国) transcriptome lineages of a proto-vertebrate. Nature 571, 349-354.

6. Zeng, A., Li, H., Guo, L., Gao, X., McKinney, S., Wang, Y., Yu, Z., Park, J., Semerad, C., Ross, E., Cheng, L.C., Davies, E., Lei, K., Wang, W., Perera, A., Hall, K., Peak, A., Box, A., Sanchez Alvarado, A., 2018. Prospectively Isolated Tetraspanin(+) Neoblasts Are Adult Pluripotent Stem 云顶集团(中国)s Underlying Planaria Regeneration. 云顶集团(中国) 173, 1593-1608 e1520.

7. Wang, W., Tindell, N., Yan, S., Yoder, J.H., 2013. Homeotic functions of the Teashirt transcription factor during adult Drosophila development. Biology open 2, 18-29.

8. Wang, W., Yoder, J.H., 2012. Hox-mediated regulation of doublesex sculpts sex-specific abdomen morphology in Drosophila. Dev Dyn 241, 1076-1090.

9. Wang, W., Kidd, B.J., Carroll, S.B., Yoder, J.H., 2011. Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila. Proc Natl Acad Sci U S A 108, 11139-11144.

10. Wang, W., Yoder, J.H., 2011. Drosophila pupal abdomen immunohistochemistry. J. Vis. Exp. (56), e3139, doi:10.3791/3139

Book chapters and Protocols:

1. Wei Wang #, Nicolas Rohner #, and Yongfu Wang #. Book Series: Emerging Model Organisms, Neuromethods, volume 194, volume 194, 2023 (http://doi.org/10.1007/978-1-0716-2875-1). (# Corresponding Editors).

2. Yufei Lou, Weifeng Lin , Wei Wang, 2023. Efficient Transgenesis in African Turquoise Killifish Using a Gibson Assembly–Based Tol2 Transposon System. Cold Spring Harb Protoc.

3. Ortega Granillo, A. , Schnittker, R. , Wang, W #., and Alvarado, A. S #.(2023). Quantifying 云顶集团(中国) proliferation through immunofluorescence on whole-mount and cryosectioned regenerating caudal fins in African killifish. Bio Protoc. Dec 20;13(24):e4908.