青年研究员
电话：
邮箱：xianjiang_lan@fudan.edu.cn
地址：上海市东安路131号复旦大学上海医学院科研二号楼CB2-020
个人简介
2016-2021年 美国费城儿童医院 血液系 博士后
2011-2016年 美国德克萨斯大学休斯敦健康科学中心&MD安德森癌症中心 表观遗传学和分子肿瘤发生 博士
研究工作主要围绕基因表达调控，表观遗传修饰在疾病包括血液病，肿瘤以及神经退行性疾病发生发展中的作用。国际上率先利用分类CRISPR-Cas9文库高通量筛选技术发现多个具有成药潜能的胎儿血红蛋白调控子，并揭示了其详细调控机制，为治疗地中海贫血症和镰刀型贫血症提供新靶点。近五年以第一或者共同第一在Science, Mol Cell, Cell Reports等国际著名期刊上发表多篇研究论文。
主要研究方向
1）结合高通量CRISPR文库筛选技术，生物化学，多组学，高通量测序，生物信息学等全面解析血红蛋白基因表达调控机制，鉴定具有治疗地中海贫血症潜能的新靶点，合作开发和测试具有治疗地中海贫血症潜能的小分子抑制剂。
2）解析极端特异转录因子ZNF410在发育和疾病中的功能。
3）推广高通量分类CRISPR文库筛选技术在肝癌耐药等疾病模型中的应用。
荣誉及获奖情况
2021年 上海海外高层次人才计划
2021年 复旦大学地高建项目-“卓越2025”人才培育计划
2019-2021 Cooley’s Anemia Foundation Research Fellowship
2020 Outstanding Abstract Achievement Award (the highest scoring abstract), ASH
2018 Abstract Achievement Award, ASH
代表性成果
1.Lan, X., Ren, R., Feng, R., Ly, L.C., Lan, Y., Zhang, Z., Aboreden, N., Qin, K., Horton, J.R., Grevet, J.D., et al. (2021). ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression. Mol Cell 81, 239-254 e238. (Preview in Mol Cell)
2.Peslak SA, Khandros E, Huang P, Lan X, Geronimo CL, Grevet JD, Abdulmalik O, Zhang Z, Giardine BM, Keller CA, Shi J, Hardison RC, Blobel GA. HRI depletion cooperates with pharmacologic inducers to elevate fetal hemoglobin and reduce sickle cell formation. Blood Adv. 2020 Sep 22;4(18):4560-4572.
3.Huang P, Peslak SA, Lan X, Khandros E, Yano JA, Sharma M, Keller CA, Giardine B, Qin K, Abdulmalik O, Hardison RC, Shi J, Blobel GA. The HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression. Blood. 2020 Jun 11;135(24):2121-2132.
4.Lan X, Khandros E, Huang P, Peslak SA, Bhardwaj SK, Grevet JD, Abdulmalik O, Wang H, Keller CA, Giardine B, Baeza J, Duffner ER, El Demerdash O, Wu XS, Vakoc CR, Garcia BA, Hardison RC, Shi J, Blobel GA. The E3 ligase adaptor molecule SPOP regulates fetal hemoglobin levels in adult erythroid cells. Blood Adv. 2019 May 28;3(10):1586-1597.
5.Grevet JD*, Lan X* Hamagami N, Edwards CR, Sankaranarayanan L, Ji X, Bhardwaj SK, Face CJ, Posocco DF, Abdulmalik O, Keller CA, Giardine B, Sidoli S, Garcia BA, Chou ST, Liebhaber SA, Hardison RC, Shi J, Blobel GA. Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells. Science. 2018 Jul 20;361(6399):285-290. (* equal contribution)
6.Lan X, Atanassov BS, Li W, Zhang Y, Florens L, Mohan RD, Galardy PJ, Washburn MP, Workman JL, Dent SYR. USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B. Cell Rep. 2016 Nov 22;17(9):2382-2393.
7.Li W, Atanassov BS, Lan X, Mohan RD, Swanson SK, Farria AT, Florens L, Washburn MP, Workman JL, Dent SY. Cytoplasmic ATXN7L3B Interferes with Nuclear Functions of the SAGA Deubiquitinase Module. Mol Cell Biol. 2016 Nov 15;36(22):2855-2866.
8.Atanassov BS, Mohan RD, Lan X, Kuang X, Lu Y, Lin K, McIvor E, Li W, Zhang Y, Florens L, Byrum SD, Mackintosh SG, Calhoun-Davis T, Koutelou E, Wang L, Tang DG, Tackett AJ, Washburn MP, Workman JL, Dent SY. ATXN7L3 and ENY2 Coordinate Activity of Multiple H2B Deubiquitinases Important for Cellular Proliferation and Tumor Growth. Mol Cell. 2016 May 19;62(4):558-71.
9.Lan X*, Koutelou E*, Schibler AC, Chen YC, Grant PA, Dent SY. Poly(Q) Expansions in ATXN7 Affect Solubility but Not Activity of the SAGA Deubiquitinating Module. Mol Cell Biol. 2015 May;35(10):1777-87. (* equal contribution)