• 方向一  脑胶质瘤的发病机理与治疗方案

• 方向二  神经肌肉罕见病的机制与基因治疗

脑胶质瘤(glioma)是脑内肿瘤的主要形式，其中，绝大多数的WHOII/III级脑胶质瘤都存在IDH基因的突变。此类肿瘤在脑内浸润性生长，且由于病变部位的特殊性，目前对低度脑胶质瘤的治疗仅限于放/化疗结合手术切除，没有靶向治疗方案。本课题组致力于寻找IDH突变型脑胶质瘤的内在缺陷，从而建立新型的潜在靶向治疗方案。目前主要学术成绩包括：1).发现IDH突变导致同源重组缺陷，导致肿瘤细胞在DNA修复方面的缺陷，通过使用PARP抑制剂与放射疗法相结合的方法，特异性杀死肿瘤细胞(Science Advances, 2020)。2).发现IDH突变型脑胶质瘤中的ATRX突变型亚型，由于其内部G-quadruplex(G4)水平增高，导致对G4特异性稳定剂敏感度大幅上升，从而被特异性杀死(Nature Communications, 2019)。3).通过表观基因组的方法，阐述IDH及ATRX突变型脑胶质瘤在时间轴上的变化及可能致病机制(Nature Genetics, 2018;Nature Communications, 2018)。

• 2020浦江人才计划

发表论文：

• Wang Y, Wild AT, Turcan S, Wu W,Sigel C, Klimtra D, Ma X, Gong Y, Holland EC, Huse JT, Chan TA, Targeting therapeutic vulnerabilities with PARP inhibition and radiation in IDH-mutant gliomas and cholangiocarcinomas, Science Advances, 2020, 22 (6), eaaz3221 IF=12.804

• Wang Y, Yang J, Wild AT, Wu W, Shah R, Danussi C, Riggins GJ, Kannan K, Sulman EP, Chan TA, and Huse JT, G-quadruplex DNA drives genomic instability and represents a targetable molecular abnormality in ATRX-deficient malignant glioma, Nature Communications, 2019, 10 (1), 943, IF=12.353

• Turcan S, Makarov V, Taranda J, Wang Y, Fabius AWM, Wu W, Zheng Y, ... Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence, Nature genetics,2018, 50 (1), 62, IF=27.125

• Danussi C, Bose P, Parthasarathy PT, Silberman PC, Arnam JSV, Vitucci M, Tang OY, Heguy A, Wang Y, Chan TA, Riggins GJ, Sulman EP, Lang P, Creighton CJ, Deneen B, Miller CY, Picketts DJ, Kannan K, Huse JT, Atrx inactivation drives disease-defining phenotypes in glioma cells of origin through global epigenomic remodeling, Nature communications, 2018, 9 (1), 1057, IF=12.353

• Wang Y, Zhu L, Kuokkanen S, and Pollard JW, Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC–ERK1/2–mTOR signaling pathway, Proc Natl Acad Sci U S A. 2015, 112(11): E1382, IF=9.504

• Wang Y, Feng H, Bi C, Zhu L, Pollard JW, Chen B, GSK-3β mediates in the progesterone inhibition of estrogen induced cyclin D2 nuclear localization and cell proliferation in cyclin D1−/− mouse uterine epithelium, FEBS Lett. 2007, 581(16): 3069, IF=2.999