科研簡介: 視網膜母細胞瘤蛋白基因(RB1)是第一個被鑒定和克隆的抑癌基因,其蛋白pRb通過結合并抑制E2F家族轉錄因子,參與細胞周期調控、抑制細胞增殖、誘導細胞衰老及凋亡。RB1基因在癌癥中突變率較高,以pRb通路為靶點的癌癥治療方案正受到越來越多的關注。代表性成果: 1.首次發現E2F1從“促增殖”向“促凋亡”轉變的分子開關Skp2,并闡明其作用機制。靶向Skp2為RB1基因缺失相關的腫瘤個體化治療,提供了藥物靶點與理論依據。(Nature Communication,2014,IF:11.34,第一作者) 2.靶向結合Skp2/Cks1口袋的小分子化合物C1在小鼠模型和類器官(organoid)模型中有效阻止轉移性激素抵抗前列腺癌生長,促進以Skp2為靶點的癌癥精準醫療的轉化。(Oncogene,2016,IF:8.46,共第一作者) 3. 首次報道pRb作為肥胖抑制因子的新功能及其作用機制,證實POMC神經元中pRb磷酸化是高脂喂飼誘導肥胖癥的成因。該成果為通過小分子激酶抑制劑防止pRb磷酸化、防治肥胖癥奠定了理論基礎。(The EMBO Journal,2013, IF:10.8,第一作者) |
代表性論文:(*為通訊作者) 1. Lu Z, Marcelin G, Bauzon F, Wang H, Fu H, Dun SL, Zhao H, Li X, Jo YH, Wardlaw S et al: pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location. EMBO J 2013, 32(6):844-857. 2. Lu Z, Bauzon F, Fu H, Cui J, Zhao H, Nakayama K, Nakayama KI, Zhu L: Skp2 suppresses apoptosis in Rb1-deficient tumours by limiting E2F1 activity. Nat Commun 2014, 5:3463. 3. Zhao H*, Lu Z*, Bauzon F, Fu H, Cui J, Locker J, Zhu L: p27T187A knockin identifies Skp2/Cks1 pocket inhibitors for advanced prostate cancer. Oncogene 2016. (*:co-first author) 4. Zhu L, Lu Z, Zhao H: Antitumor mechanisms when pRb and p53 are genetically inactivated. Oncogene 2015, 34(35):4547-4557. 5. Zhao H, Bauzon F, Lu Z, Cui J, Nakayama K, Nakayama KI, Locker J, Zhu L: Skp2 Deletion Unmasks a p27 Safeguard that Blocks Tumorigenesis in the Absence of pRb and p53 Tumor Suppressors. Cancer Cell 2013, 24(5):645 6. Lu Z, Kong X, Lu Z, Xiao M, Chen M, Zhu L, Shen Y, Hu X, Song S: Para-aminobenzoic acid (PABA) synthase enhances thermotolerance of mushroom Agaricus bisporus. PLoS One 2014, 9(3):e91298. 7. Lu Z, Li W, Yang Y, Hu X: Isolation and characterization of 19 new microsatellite loci in Colocasia esculenta (Araceae). American journal of botany 2011, 98(9):e239-241. |