王伟 博士

北京生命科学研究所研究员

Wei Wang, Ph.D.

Assistant Investigator,  NIBS, Beijing，China

Email: wangwei@nibs.ac.cn

Home page: https://killifishlab.com/

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

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

2021-Present 北京生命科学研究所研究员

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

2014-2021年 美国斯托瓦斯医学研究所、霍华德·休斯医学研究所博士后

器官再生是21世纪生命科学研究的焦点之一。由于具有帮助人类恢复因疾病、衰老或其它原因造成的器官损伤的潜力，器官再生在生物医学领域一直具有很大的吸引力。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，高等哺乳动物（包括人类）却在进化过程中丢失了这些能力。此外，器官再生能力在衰老过程中逐渐减弱，导致老年动物生活质量显著下降。迄今为止，再生能力在进化和衰老过程中是如何丢失的仍是生物学中未解的难题。借助具有显著优势的非洲鳉鱼（Nothobranchius furzeri）模型，我们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，并以其为靶标通过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。强大的干旱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，仅为斑马鱼所需时间的一半），极大地节省了遗传操作和实验时间； 2）胚胎可以进入滞育或休眠长达两年以上，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4-6个月），是目前实验室可饲养的寿命最短的脊椎动物模型； 4）由于早期胚胎发育缓慢， CRISPR/Cas9、Tol2介导的转基因和PhiC31介导的位点特异性转基因等遗传操作效率高。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. Further, the ability to regenerate damaged organs displays progressive decline during aging, leading to reduced quality of life in old animals. How the regenerative capacities are lost during evolution and aging is still a long-standing question in biology. Powered with a new genetic model, the African killifish Nothobranchius furzeri, the Wang Lab is interested in identifying molecular mechanisms of regenerative capacities that can be targeted to help humans rebuild damaged and aged organs. Our current research will focus on, but not limited to, the following areas:

(1) The molecular basis of spinal cord regeneration.

(2) Evolution of regenerative capacities in vertebrates.

(3) Regeneration and Rejuvenation.

Research articles:

1.  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 cell pluripotency, Proc Natl Acad Sci U S A, 119 (40) e2204716119. (# Corresponding Authors)

2.  Xiong, SL., Wang, W., Kenzior, A., Olsen, L., Krishnan, J., Persons, J., Medley, K., Peuß, R., Wang, YF., Chen, SY., Zhang, N., Thomas, N., Miles, JM., Sánchez Alvarado, A., Rohner, N., 2022, Enhanced lipogenesis through Pparg helps cavefish adapt to food scarcity, Current Biology 32, 1–9.

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. https://www.nature.com/articles/d41586-020-02529-5

Research Highlights in Nature Reviews Genetics: Enhancing regeneration.

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

4.  Kushawah G., Hernandez-Huertas L., Abugattas-Nuñez del Prado J., Martinez-Morales J.R., DeVore M.L., Hassan H., Moreno-Sanchez I., Tomas-Gallardo L., Diaz-Moscoso A., Monges D.C.; Guelfo J.R., Theune W.C., Brannan E.O., Wang W., Corbin T.J., Moran A.M., Sánchez Alvarado A., Málaga-Trillo E., Takacs C.M., Bazzini A.; Moreno-Mateos M., 2020. CRISPR-Cas13d induces efficient mRNA knock-down in animal embryos, Dev. Cell 54, 1–13.

5.  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.

6.  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-cell transcriptome lineages of a proto-vertebrate. Nature 571, 349-354.

7.  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 Cells Underlying Planaria Regeneration. Cell 173, 1593-1608 e1520.

8.  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.

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

10. 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.

11. 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, In press (https://link.springer.com/book/9781071628744). (# Corresponding Editors).

2.  Ortega Granillo, A., Schnittker, R., Wang, W #. and Alvarado, A.S#. (2021). Quantifying cell proliferation through immunofluorescence on whole-mount and cryosectioned regenerating caudal fins in African killifish. Bio-protocol. bio-protocol.org/prep1480. (# Corresponding Authors)