王偉 博士

北京生命科學(xué)研究所研究員

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 北京生命科學(xué)研究所研究員

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

2014-2021年 美國斯托瓦斯醫(yī)學(xué)研究所、霍華德·休斯醫(yī)學(xué)研究所博士后

器官再生是21世紀生命科學(xué)研究的焦點之一。由于具有幫助人類恢復(fù)因疾病、衰老或其它原因造成的器官損傷的潛力，器官再生在生物醫(yī)學(xué)領(lǐng)域一直具有很大的吸引力。低等脊椎生物（例如魚類、蠑螈等）具有極強的器官再生能力，他們可以完美地修復(fù)受損的心臟、大腦、脊髓及肢體；相比之下，高等哺乳動物（包括人類）卻在進化過程中丟失了這些能力。此外，器官再生能力在衰老過程中逐漸減弱，導(dǎo)致老年動物生活質(zhì)量顯著下降。迄今為止，再生能力在進化和衰老過程中是如何丟失的仍是生物學(xué)中未解的難題。借助具有顯著優(yōu)勢的非洲鳉魚（Nothobranchius furzeri）模型，我們實驗室的主要研究興趣是鑒定賦予器官再生能力的核心分子機制，并以其為靶標通過再生醫(yī)學(xué)手段探索人類受損器官的重建。

非洲鳉魚棲息在非洲東南部遭受季節(jié)性干旱的臨時水塘中。成年的非洲鳉魚僅在雨季池塘蓄水時才會出現(xiàn)。在干旱無水的季節(jié)，非洲鳉魚以被埋在泥中且處于滯育（diapause）或休眠狀態(tài)的胚胎形式存活，等待下一個雨季孵化并再次繁殖。強大的干旱選擇壓力使得該物種進化出了獨有的特征，這些特征可以大大加速器官發(fā)育、再生及衰老相關(guān)的研究：1）生長及性成熟速度快（野外14天即可性成熟，實驗室條件下30-45天可性成熟，僅為斑馬魚所需時間的一半），極大地節(jié)省了遺傳操作和實驗時間； 2）胚胎可以進入滯育或休眠長達兩年以上，使得遺傳品系的長期保存方便且費用低，無需像其他動物模型需要長期飼養(yǎng)成年動物； 3）在實驗室條件下衰老速度極快（平均壽命為4-6個月），是目前實驗室可飼養(yǎng)的壽命最短的脊椎動物模型； 4）由于早期胚胎發(fā)育緩慢， CRISPR/Cas9、Tol2介導(dǎo)的轉(zhuǎn)基因和PhiC31介導(dǎo)的位點特異性轉(zhuǎn)基因等遺傳操作效率高?？傊侵搠汈~為成年動物器官發(fā)育、再生和衰老研究帶來了傳統(tǒng)模型所缺乏的顯著優(yōu)勢和全新機遇。

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., Peu?, 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-Nu?ez 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)