基本信息
李令杰
干細(xì)胞分化發(fā)育與疾病的表觀遺傳調(diào)控研究組
電話：63846590-776901
郵箱：[email protected]
研究方向
本實驗室的主要研究興趣為細(xì)胞命運(yùn)的決定機(jī)制，目前專注于皮膚分化發(fā)育的表觀基因組調(diào)控以及再生醫(yī)學(xué)研究。實驗室以上皮系統(tǒng)特別是皮膚器官為主要研究對象，運(yùn)用多種表觀基因組分析技術(shù)，并結(jié)合體外干細(xì)胞分化與體內(nèi)發(fā)育模型來深入理解：早期外胚層及上皮組織譜系特化、穩(wěn)態(tài)平衡、衰老及相關(guān)疾病發(fā)生的調(diào)控機(jī)制；在此基礎(chǔ)上進(jìn)一步發(fā)展干細(xì)胞及基因組新技術(shù)/方法用于再生醫(yī)學(xué)及復(fù)雜疾病的診治。
過往的研究成績包括：發(fā)現(xiàn)干細(xì)胞命運(yùn)關(guān)鍵蛋白Stk40，并揭示該蛋白調(diào)控核內(nèi)轉(zhuǎn)錄因子與外界信號通路之間的應(yīng)答機(jī)制（PNAS 2010）；構(gòu)建動物模型并揭示出長鏈非編碼RNA 調(diào)控胚胎發(fā)育、腫瘤和基因組中染色質(zhì)失活的重要功能（Cell Rep.2013, Elfie 2022）; 合作開發(fā)出人皮膚干細(xì)胞分化系統(tǒng)用于治療遺傳性皮膚缺損癥以及類器官模型用于皮膚再生與藥物篩選，并系統(tǒng)揭示出外胚層及皮膚發(fā)育各階段的表觀基因組調(diào)控規(guī)律（Cell Stem Cell 2019）；建立單細(xì)胞發(fā)育潛能以及染色質(zhì)互作的生信分析工具，促進(jìn)對細(xì)胞命運(yùn)調(diào)控機(jī)理的研究(Brief Bioinform 2022, 2023)。
個人簡歷
目前擔(dān)任上海交通大學(xué)基礎(chǔ)醫(yī)學(xué)院組織胚胎學(xué)與遺傳發(fā)育學(xué)系課題組長，博士生導(dǎo)師。西北大學(xué)生物技術(shù)專業(yè)學(xué)士，中科院上海生命科學(xué)研究院發(fā)育生物學(xué)博士，美國斯坦福大學(xué)博士后及Research Associate。主要研究成果發(fā)表在Cell Stem Cell，Cell Rep，PNAS，Brief Bioinform, Elfie等國際知名期刊共20多篇。研究成果獲得過教育部自然科學(xué)二等獎、上海市自然科學(xué)三等獎、第64屆國際皮膚生物學(xué)年會青年科學(xué)家獎（64th Annual Montagna Symposium on the Biology of Skin, Travel Award for Young Investigators）等多項榮譽(yù)。實驗室研究工作目前獲得國家科技部、自然基金委、上海市科委以及高層次人才計劃等基金資助。
科研項目
1. 轉(zhuǎn)錄因子TFAP2C招募BRD9調(diào)控染色質(zhì)空間互作的重塑和體表外胚層分化命運(yùn)的機(jī)制研究，國家自然科學(xué)基金委面上項目，2025-2028，課題負(fù)責(zé)人；
2. 單細(xì)胞染色質(zhì)可及性分析新工具用于復(fù)雜性疾病的精準(zhǔn)分型與致病機(jī)制研究 轉(zhuǎn)化醫(yī)學(xué)中心開放課題項目，2025-2026，課題負(fù)責(zé)人；
3. 細(xì)胞周期和DNA甲基化在多能性建立、維持和退出過程中的功能和機(jī)制研究，科技部重點研發(fā)計劃， 2021-2026，項目子課題負(fù)責(zé)人；
4. 皮膚分化早期細(xì)胞群體的異質(zhì)性及功能與調(diào)節(jié)機(jī)制的研究，國家自然科學(xué)基金委面上項目，2021-2024，課題負(fù)責(zé)人；
5. TFAP2C調(diào)控體表外胚層干細(xì)胞分化潛能的表觀遺傳學(xué)機(jī)制，上海市科委項目，2021-2024，課題負(fù)責(zé)人
6. 上海高層次人才計劃，上海市教委，2019-2021，課題負(fù)責(zé)人
7. 上海交通大學(xué)醫(yī)學(xué)院新課題組啟動經(jīng)費(fèi), 課題負(fù)責(zé)人。
論文與專著
1) Wang, Y.; Ding, X.; Zhang, F.; Xie, X.; Yang, C.; Wang, Z.; Cai, X.; Li, Q.; Li, L.*; Chen, X*.; Dai, F*.; Zhang, S*. Ultrasmall Cu2I2 Nanoclusters Trigger Metabolic-Epigenetic Reprogramming and Endogenous Antioxidant Systems for Alleviating Osteoarthritis. Chem. Eng. J. 2024, 154568.
2) Zhang F*, Jiao H, Wang Y, Yang C, Li L, Wang Z, Tong R, Zhou J, Shen J, Li L*. InferLoop: leveraging single-cell chromatin accessibility for the signal of chromatin loop. Brief Bioinform. 2023 May 19;24(3):bbad166. doi: 10.1093/bib/bbad166.
3) Lan L, Zhang X, Yang S, Li L*, Mao X*. Chromosome-level genome assembly of the Stoliczka's Asian trident bat (Aselliscus stoliczkanus). Sci Data. 2023;10(1):902. Published 2023 Dec 15. doi:10.1038/s41597-023-02838-0
4) Ma Q*, Yang L, Tolentino K, Wang G, Zhao Y, Litzenburger UM, Shi Q, Zhu L, Yang C, Jiao H, Zhang F, Li R, Tsai MC, Chen JA, Lai I, Zeng H, Li L*, Chang HY*. Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis. Elife. 2022 Dec 29;11:e79126. doi: 10.7554/eLife.79126.
5) Zhang F*, Yang C, Wang Y, Jiao H, Wang Z, Shen J, Li L*. FitDevo: accurate inference of single-cell developmental potential using sample-specific gene weight. Brief Bioinform. 2022 Sep 20;23(5):bbac293. doi: 10.1093/bib/bbac293.
6) Li L, Wang Y, Torkelson JL, Shankar G, Pattison J, H Zhen, Duren Z, Fang F, Melo S, Piekos S, Li J, Liaw E, Chen L, Li R, Wernig M, Wong WH, Chang HY, Oro AE. TFAP2C- and p63-Dependent Networks Sequentially Rearrange Chromatin Landscapes to Drive Human Epidermal Lineage Commitment. Cell Stem Cell 2019 24:271-284
7) Li L, Helms JA, Chang HY. Comment on "Hotair Is Dispensable for Mouse Development". PLoS Genetics. 2016 Dec 15;12(12):e1006406. doi: 10.1371/journal.pgen.1006406. eCollection 2016.
8) Li L, Chang HY. Physiological roles of long noncoding RNAs: insight from knockout mice. Trends in Cell Biology. 2014 24(10): 594-602.
9) Li L, Liu B, Wapinski OL, Tsai MC, Qu K, Zhang J, Carlson JC, Lin M, Fang F, Gupta RA, Helms JA, Chang HY. Targeted disruption of Hotair leads to homeotic transformation and gene derepression. Cell Reports. 2013 5(1): 3-12.
10) Li L, Sun L, Gao F, Jiang J, Yang Y, Li C, Gu J, Wei Z, Yang A, Lu R, Ma Y, Tang F, Won Kwon S, Zhao Y, Li J, Jin Y. Stk40 links the pluripotency factor Oct4 to the Erk/MAPK pathway and controls extraembryonic endoderm differentiation. PNAS. 2010 107(4): 1402-7.
11) Neumayer G, Torkelson JL, Li S, McCarthy K, Zhen HH, Vangipuram M, Mader MM, Gebeyehu G, Jaouni TM, Jacków-Malinowska J, Rami A, Hansen C, Guo Z, Gaddam S, Tate KM, Pappalardo A, Li L, Chow GM, Roy KR, Nguyen TM, Tanabe K, McGrath PS, Cramer A, Bruckner A, Bilousova G, Roop D, Tang JY, Christiano A, Steinmetz LM, Wernig M, Oro AE. A scalable and cGMP-compatible autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa. Nat Commun. 2024 Jul 11;15(1):5834.
12) Zhu T, Li Q, Zhang Z, Shi J, Li Y, Zhang F, Li L, Song X, Shen J, Jia R. ARID1A loss promotes RNA editing of CDK13 in an ADAR1-dependent manner. BMC Biol. 2024 Jun 5;22(1):132.
13) Yao, T., Zhang, Z., Li, Q., Huang, R., Hong, Y., Li, C., Zhang, F., Huang, Y., Fang, Y., Cao, Q., Jin, X., Li, C., Wang, Z., Lin, X. J., Li, L., Wei, W., Wang, Z., & Shen, J. Long-Read Sequencing Reveals Alternative Splicing-Driven, Shared Immunogenic Neoepitopes Regardless of SF3B1 Status in Uveal Melanoma. Cancer Immunol Res, 2023,11(12), 1671–1687.
14) Fang F, Cao W, Mu Y, Okuyama H, Li L, Qiu J, Weyand CM, Goronzy JJ. IL-4 prevents adenosine-mediated immunoregulation by inhibiting CD39 expression. JCI Insight. 2022 Jun 22;7(12):e157509. doi: 10.1172/jci.insight.157509.
15) Yang W, He H, Wang T, Su N, Zhang F, Jiang K, Zhu J, Zhang C, Niu K, Wang L, Yuan X, Liu N, Li L, Wei W, Hu J. Single-Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell-Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice. Hepatology. 2021 Nov;74(5):2774-2790. doi: 10.1002/hep.31987.
16) Fang F, Cao W, Zhu W, Lam N, Li L, Gaddam S, Wang Y, Kim C, Lambert S, Zhang H, Hu B, Farber DL, Weyand CM, Goronzy JJ. The cell-surface 5'-nucleotidase CD73 defines a functional T memory cell subset that declines with age. Cell Reports. 2021 Nov 9;37(6):109981. doi: 10.1016/j.celrep.2021.109981.
17)Fang J, Ma Q, Chu C, Huang B, Li L, Cai P, Batista PJ, Tolentino KEM, Xu J, Li R, Du P, Qu K, Chang HY. PIRCh-seq: functional classification of non-coding RNAs associated with distinct histone modifications. Genome Biol. 2019; 20: 292.
18) Pattison JM, Melo SP, Piekos SN, Torkelson JL, Bashkirova E, Mumbach MR, Rajasingh C, Zhen HH, Li L, Liaw E, Alber D, Rubin AJ, Shankar G, Bao X, Chang HY, Khavari PA, Oro AE. Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment. Nature Genetics. 2018 Nov 5. doi: 10.1038/s41588-018-0263-0.
19) Batista PJ, Molinie B, Wang J, Qu K, Zhang J, Li L, Bouley DM, Lujan E, Haddad B, Daneshvar K, Carter AC, Flynn RA, Zhou C, Lim KS, Dedon P, Wernig M, Mullen AC, Xing Y, Giallourakis CC, Chang HY. m6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell. 2014 15 (6): 707-719.
20) Sebastiano V, Zhen HH, Haddad B, Bashkirova E, Melo SP, Wang P, Leung TL, Siprashvili Z, Tichy A, Li J, Ameen M, Hawkins J, Lee S, Li L, Schwertschkow A, Bauer G, Lisowski L, Kay MA, Kim SK, Lane AT, Wernig M, Oro AE. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Science Translational Medicine. 2014 6(264): 264ra163.
21) Yu H, He K, Li L, Sun L, Tang F, Li R, Ning W, Jin Y. Deletion of STK40 protein in mice causes respiratory failure and death at birth. Journal of Biological Chemistry. 2013 288 (8), 5342-5352.
