研究組長(zhǎng)介紹
張明亮,研究員,博士生導(dǎo)師,上海市“浦江人才”,上海市東方學(xué)者特聘教授。2002年畢業(yè)于廈門大學(xué),獲得學(xué)士學(xué)位;2009年畢業(yè)于中國(guó)科學(xué)院生物化學(xué)與細(xì)胞生物學(xué)研究所,獲得博士學(xué)位;2010-2016年分別在美國(guó)斯克里普斯研究所(Scripps Research Institute)和美國(guó)加州大學(xué)舊金山分校格拉德斯通研究所(The J. David Gladstone Institutes)從事博士后研究;2016年起加入上海交通大學(xué)醫(yī)學(xué)院組織胚胎學(xué)與遺傳發(fā)育學(xué)系,任支部書記,常務(wù)副主任。現(xiàn)任中國(guó)細(xì)胞生物學(xué)會(huì)青年工作委員會(huì)委員、中國(guó)醫(yī)師協(xié)會(huì)基礎(chǔ)研究與臨床轉(zhuǎn)化專業(yè)委員會(huì)(學(xué)組)委員、中國(guó)醫(yī)藥生物技術(shù)協(xié)會(huì)神經(jīng)修復(fù)在再生分會(huì)委員、上海市生殖醫(yī)學(xué)重點(diǎn)實(shí)驗(yàn)室特聘研究員。課題組聚焦于利用化學(xué)手段高效特異的誘導(dǎo)產(chǎn)生神經(jīng)系統(tǒng)的干/祖細(xì)胞和終末分化細(xì)胞,并將化學(xué)策略應(yīng)用于體內(nèi),實(shí)現(xiàn)內(nèi)源細(xì)胞的原位再生;研發(fā)針對(duì)神經(jīng)系統(tǒng)疾病的細(xì)胞/化學(xué)藥,推動(dòng)神經(jīng)損傷修復(fù)與再生。
研究方向與進(jìn)展
課題組聚焦于利用化學(xué)手段高效特異性的誘導(dǎo)產(chǎn)生神經(jīng)系統(tǒng)的干/祖細(xì)胞和終末分化細(xì)胞,并將化學(xué)策略應(yīng)用于體內(nèi),實(shí)現(xiàn)內(nèi)源細(xì)胞的原位再生的研究;利用重編程和干細(xì)胞分化模型研究細(xì)胞命運(yùn)轉(zhuǎn)變的調(diào)控機(jī)制,提高重編程/分化的效率和特異性;研發(fā)針對(duì)神經(jīng)系統(tǒng)疾病的細(xì)胞藥,并研究其作用機(jī)制。參與細(xì)胞藥物標(biāo)準(zhǔn)研究和制定,為推動(dòng)針對(duì)神經(jīng)系統(tǒng)損傷和退行性疾病的干細(xì)胞療法和藥物研發(fā)提供線索。課題組的長(zhǎng)期研究目標(biāo)是深入理解細(xì)胞命運(yùn)決定機(jī)制,研發(fā)體外和體內(nèi)定向誘導(dǎo)產(chǎn)生疾病治療所需細(xì)胞的技術(shù),推動(dòng)干細(xì)胞治療的臨床轉(zhuǎn)化。張明亮研究員主要研究細(xì)胞重編程/轉(zhuǎn)分化的分子機(jī)制, 實(shí)現(xiàn)了小分子誘導(dǎo)細(xì)胞重編程、體細(xì)胞的體外擴(kuò)增等目標(biāo)(Cell Rep., 2019, 2020; J. Mol. Cell Biol., 2019; Stem Cells Transl. Med., 2013; chapter in Principles Dev. Genet., 2014),研發(fā)定向轉(zhuǎn)分化的調(diào)控機(jī)制和利用化學(xué)小分子誘導(dǎo)產(chǎn)生多種細(xì)胞類型的原創(chuàng)性技術(shù)(Cell Stem Cell, 2016; Science, 2016; Nat. Commun., 2016; Stem Cells Dev., 2016; Cell Res., 2014)。迄今在細(xì)胞命運(yùn)調(diào)控方面取得的原創(chuàng)性成果在國(guó)際知名期刊發(fā)表論文十余篇,為遺傳和發(fā)育生物學(xué)領(lǐng)域?qū)W術(shù)專著《Principles of Developmental Genetics》撰寫“Chemical Approaches to Controlling Cell Fate”章節(jié)(2014),并以第一申請(qǐng)人獲國(guó)際專利1 項(xiàng) (2017)。研究成果被中國(guó)兩院院士評(píng)為“2016 世界十大科技進(jìn)展”之一,被Cell、Nature、Faculty of 1000 等期刊/媒體高度評(píng)價(jià),為研發(fā)針對(duì)神經(jīng)損傷/退行性疾病的干細(xì)胞療法奠定了理論和技術(shù)基礎(chǔ)。研究工作得到科技部干細(xì)胞重點(diǎn)專項(xiàng),國(guó)家自然科學(xué)基金委面上項(xiàng)目,上海市科委基礎(chǔ)重點(diǎn)項(xiàng)目,上海市浦江人才科研項(xiàng)目等科研基金支持。張明亮研究員獲得上海市東方學(xué)者特聘教授,上海市浦江人才稱號(hào)。
科研項(xiàng)目
(1)科技部干細(xì)胞重點(diǎn)專項(xiàng)子課題
(2)國(guó)家自然科學(xué)基金委面上項(xiàng)目
(3)上海市科委基礎(chǔ)研究領(lǐng)域項(xiàng)目
(4)上海市“浦江人才計(jì)劃-A類”
(5)上海高層次人才
代表性論文、專著與專利
1.Cheng Zhouli, et al. The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming. Cell Reports (2020) 32(2):107877.
2.Sun Pingxin, et al. Maintenance of primary hepatocyte functions in vitro by inhibiting mechanical tension-induced YAP activation. Cell Rep. 2019 Dec 3;29(10):3212-3222.e4.
3.Liu Chang, et al. Conversion of mouse fibroblasts into oligodendrocyte progenitor-like cells through a chemical approach. Journal of Molecular Cell Biology (2019) 11(6):489-495.
4.Zhang Mingliang, et al. Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation. Cell Stem Cell (2016) 18 (5):653-667.
5.Cao Nan, et al. Conversion of Human Fibroblasts into Functional Cardiomyocytes by Small Molecules. Science (2016) 352 (6290):1216-1220.
6.Zhu Saiyong, et al. Human pancreatic beta-like cells converted from fibroblasts. Nature Communications (2016) 7:10080.
7.Xie Fei, et al. Reversible immortalization enables seamless transdifferentiation of primary fibroblasts into other lineage cells. Stem Cells & Development (2016) 25 (16):1243-1248.
8.Zhu Saiyong, et al. Small Molecules Enable Oct4-Mediated Direct Reprogramming into Expandable Human Neural Stem Cells. Cell Research (2014) 24 (1):126-129.
9.Xu Tao, et al. Concise review: Chemical Approaches for Modulating Lineage-Specific Stem Cells and Progenitors. Stem Cells Translational Medicine (2013) 2 (5): 355-361.
10.Tong Xiajing, et al. Est1 protects telomeres and inhibits subtelomeric Y’-element recombination. Molecular & Cellular Biology (2011) 31(6):1263-1274.
11.Zhang Mingliang, et al. Yeast telomerase subunit Est1p has guanine-quadruplex promoting activity that is required for telomere elongation. Nature Structural & Molecular Biology (2010) 17 (2):202-209.
12.Liao Xinhua, et al. Characterization of recombinant Saccharomyces cerevisiae telomerase core enzyme purified from yeast. Biochemical Journal (2005) 390 (Pt 1):169-176.
學(xué)術(shù)專著章節(jié):
Zhang Mingliang#, Li Ke#, Xie Min, and Ding Sheng. Chemical Approaches to Controlling Cell Fate. in Principles of Developmental Genetics, 2nd Edition, Moody S., (2014) Academic Press. pp59-76. # co-first author
專利申請(qǐng):
Zhang Mingliang, and Ding Sheng. Chemical reprogramming to generate neuronal cells, PCT/US2016/045290, WO/2017/027280
團(tuán)隊(duì)介紹
實(shí)驗(yàn)室成立于2017年,是年輕且充滿活力的研究團(tuán)隊(duì)。實(shí)驗(yàn)室熱忱歡迎有志于從事干細(xì)胞與神經(jīng)發(fā)育/退行性疾病的學(xué)者和同學(xué)加入!課題組招聘助理研究員(具有博士學(xué)位,博士后經(jīng)歷,協(xié)助PI開展科研相關(guān)工作,給予上海交大醫(yī)學(xué)院崗位編制)、博士后(近期獲得博士學(xué)位,開展科研工作)。有興趣的學(xué)者和同學(xué)請(qǐng)聯(lián)系:[email protected],干細(xì)胞與神經(jīng)發(fā)育/退行性疾病研究組期待你的加盟!
