浦江人才

祝颖慧

Z

发布时间:2019-05-08  

姓名:祝颖慧


导师情况:博士生导师

研究领域:白血病耐药及靶向治疗

E-mail zhuyinghui@tongji.edu.cn

通讯地址:上海市杨浦区四平路1239号,同济大学生命科学与技术学院

 

个人简介:

博士毕业于中国科学院北京基因组研究,2016年至2022年在美国希望之城国家医疗中心开展博士后及研究员工作,专注白血病的发生及耐药机制。2021年入选上海市海外高层次人才计划,2022年起任同济大学特聘研究员、博士生导师,并受聘于同济大学附属东方医院任特聘研究员。目前主持国家自然科学基金、科技部重点研发计划子课题、上海市科技创新行动计划及上海市白玉兰人才计划浦江人才项目。近年,以第一或通讯作者(含共同)在Blood (3)The Journal of Clinical InvestigationAdvanced ScienceClinical and Translational Medicine等杂志发表论文。培养研究生获得国家奖学金及上海市优秀毕业生。


研究方向:

急性白血病是一类起源于造血干/祖细胞异常克隆扩增的恶性肿瘤,发病进展快,复发率高。随着靶向治疗及化疗方式的应用不断推进,在突破患者治疗瓶颈的同时,耐药问题日益凸显,亟需深入阐明其分子机制,为精准治疗提供理论指导。

      课题组前期系统探索急性白血病的多重耐药机制:FLT3抑制剂治疗方面,发现FLT3的精氨酸甲基化修饰在急性白血病耐药形成中发挥关键作用(Blood, 2019a; Blood, 2019b; 在化疗耐药方面,构建急性髓系白血病(AML)的磷酸化特征图谱,解析关键激酶通路及分子机制(Clinical Translational Medicine, 2022; Advanced Science, 2024);针对免疫治疗耐药,合作开发了新型双特异性抗体,协同清除AML原始细胞及干细胞(Blood, 2024),并深入揭示免疫靶点CD84的作用机制(The Journal of Clinical Investigation,2025

      本课题组聚焦急性白血病的耐药机制及新靶点探索,综合应用蛋白质组学、代谢组学等多维度组学技术,系统解析代谢重编程信号通路克隆动态,识别关键调控因子与潜在干预靶点,推动新型治疗组合的机制验证与转化探索,助力精准、可持续的个体化干预方案开发。本课题组以临床问题为导向,以精准治疗为目标,诚邀有志于白血病机制研究和转化应用的博士后、研究生与本科生加入。


主要研究方向:

1. 基于多组学技术解析急性白血病耐药机制

2. 急性白血病新型靶点筛选治疗策略开发

3. 造血发育及白血病耐药的代谢调控机制

3. 难治性白血病的克隆演变与治疗干预探索


代表性文章:*通讯作者, # 第一作者)


通讯作者文章:

1. Zhu Y*#, Murtadha M#, Liu M#, Caserta E, Napolitano O, Nguyen LXT, Wang H, Moloudizargari M, Nigam L, Tandoh T, Wang X, Pozhitkov A, Su R, Lin X, Estepa MD, Pillai R, Song J, Sanchez JF, Fu YH, Zhang L, Li M, Zhang B, Li L, Kuo YH, Rosen S, Marcucci G, Williams JC, Pichiorri F*. Identification of CD84 as a potent survival factor in acute myeloid leukemia. J Clin Invest. 2025 Apr 8;135(11):e176818.

2. Murtadha M#, Park M#, Zhu Y#, Caserta E, Napolitano O, Tandoh T, Moloudizargari M, Pozhitkov A, Singer M, Dona AA, Vahed H, Gonzalez A, Ly K, Ouyang C, Sanchez JF, Nigam L, Duplan A, Chowdhury A, Ghoda L, Li L, Zhang B, Krishnan A, Marcucci G*, Williams JC*, Pichiorri F*. A CD38-directed, single-chain T-cell engager targets leukemia stem cells through IFN-γ-induced CD38 expression. Blood. 2024 Apr 18;143(16):1599-1615.

3. Jin J#, Hou S#, Yao Y, Liu M, Mao L, Yang M, Tong H, Zeng T, Huang J, Zhu Y*, Wang H*. Phosphoproteomic Characterization and Kinase Signature Predict Response to Venetoclax Plus 3+7 Chemotherapy in Acute Myeloid Leukemia. Adv Sci (Weinh). 2024 Mar;11(11):e2305885.

4. Yao Y, Lin X, Wang C, Gu Y, Jin J, Zhu Y*, Wang H*. Identification of a novel NPM1 mutation in acute myeloid leukemia. Exp Hematol Oncol. 2023 Oct 4;12(1):87

5. Zhu Y#, He X, Li S, Gan Y, Li Z, Wang H, Dong H, Zhang L, Xue SL, Xu Y, Li L. Phosphoproteomics profiling reveals a kinase network conferring acute myeloid leukaemia intrinsic chemoresistance and indicates HMGA1 phosphorylation as a potential influencer. Clin Transl Med. 2022 Mar;12(3):e749. 

6. Zhu Y#, He X#, Lin YC, Dong H, Zhang L, Chen X, Wang Z, Shen Y, Li M, Wang H, Sun J, Nguyen LX, Zhang H, Jiang W, Yang Y, Chen J, Müschen M, Chen CW, Konopleva MY, Sun W, Jin J, Carlesso N, Marcucci G, Luo Y, Li L. Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia. Blood. 2019 Oct 10;134(15):1257-1268.

7. He X#, Zhu Y#, Lin YC, Li M, Du J, Dong H, Sun J, Zhu L, Wang H, Ding Z, Zhang L, Zhang L, Zhao D, Wang Z, Wu H, Zhang H, Jiang W, Xu Y, Jin J, Shen Y, Perry J, Zhao X, Zhang B, Liu S, Xue SL, Shen B, Chen CW, Chen J, Khaled S, Kuo YH, Marcucci G, Luo Y, Li L. PRMT1-mediated FLT3 arginine methylation promotes maintenance of FLT3-ITD+ acute myeloid leukemia. Blood. 2019 Aug 8;134(6):548-560. 

8. Zhu Y#, Chen X, Pan Q, Wang Y, Su S, Jiang C, Li Y, Xu N, Wu L, Lou X, Liu S. A Comprehensive Proteomics Analysis Reveals a Secretory Path- and Status-Dependent Signature of Exosomes Released from Tumor-Associated Macrophages. J Proteome Res. 2015 Oct 2;14(10):4319-31.


共共同作者文章:

1. Dona AA#, Tandoh T, Nigam L, Singer M, Caserta E, Murtadha M, Zhu Y, Moloudizargari M, Sharma P, Napolitano O, Winchester J, Chowdhury A, Pozhitkov A, Sanchez JF, Vahed H, Marcucci G, Coffey M, Nuovo G, Sborov DW, Pichiorri F*, Hofmeister CC*. Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects. J Hematol Oncol. 2025 Jan 20;18(1):1.

2. Dong H#, He X#, Zhang L#, Chen W, Lin YC, Liu SB, Wang H, Nguyen LXT, Li M, Zhu Y, Zhao D, Ghoda L, Serody J, Vincent B, Luznik L, Gojo I, Zeidner J, Su R, Chen J, Sharma R, Pirrotte P, Wu X, Hu W, Han W, Shen B, Kuo YH, Jin J, Salhotra A, Wang J, Marcucci G, Luo YL, Li L*. Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity. Nat Cancer. 2024 Apr;5(4):601-624.

3. Sun J#, He X, Zhu Y, Ding Z, Dong H, Feng Y, Du J, Wang H, Wu X, Zhang L, Yu X, Lin A, McDonald T, Zhao D, Wu H, Hua WK, Zhang B, Feng L, Tohyama K, Bhatia R, Oberdoerffer P, Chung YJ, Aplan PD, Boultwood J, Pellagatti A, Khaled S, Kortylewski M, Pichiorri F, Kuo YH, Carlesso N, Marcucci G, Jin H*, Li L*. SIRT1 Activation Disrupts Maintenance of Myelodysplastic Syndrome Stem and Progenitor Cells by Restoring TET2 Function. Cell Stem Cell. 2018 Sep 6;23(3):355-369.e9.

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