蛋白质与多肽药物所重点实验室

　　1991            同济医科大学药学院

　　1997            沈阳药科大学，获药剂学硕士

　　2000            上海医药工业研究院国家药物制剂工程研究中心，获药剂学博士学位

　　2000 - 2001 明尼苏达大学药学院药物制剂系，从事博士后研究

　　2001 - 2003 哈佛大学医学院麻省总医院和东北大学药物科学系，任Research Associate

　　2004 - 至今 中科院生物物理所研究员，蛋白质与多肽药物实验室副主任。现为中国药学会高级会员

　　1. 于TGF-alpha信号通路中关键蛋白Smad3在肝纤维化和肺纤维化中的作用机制及其作为药物设计候选靶标的确证；

　　2. 肿瘤和心血管疾病的靶向纳米给药系统的研究；

　　3. 肿瘤治疗性纳米疫苗的设计与评价。

近期主要工作和进展

　　揭示了肿瘤发生发展的新机制：我们的研究发现，组织的纤维化为肿瘤细胞的生成和发展提供了有利的微环境，纤维化可促进正常细胞向肿瘤细胞转化及增值；纤维化为肿瘤细胞提供了适宜其定居和生长的微环境并促进肿瘤转移灶的形成。TGF-alpha / Smad3信号通路在这一过程中起到关键作用可以作为药物筛选的新靶点。发现了柚皮素和柚皮苷可以特异性干预TGF-alpha / Smad3信号通路起到预防和治疗纤维化及癌症作用。

　　提出了肿瘤化疗的新观点和新思路：大多数化疗药物的作用靶点在细胞内，如阿霉素和顺铂等作用于细胞核的DNA，紫杉醇和长春新碱等作用胞浆的微管；或已具有耐药性的肿瘤细胞，通过外排机制将药物泵出细胞外，细胞内的药物浓度不足以抑制细胞的增殖。仅仅将药物输送到肿瘤组织（组织靶向）是不够的，在提高肿瘤组织选择性基础上，如何提高药物的组织渗透性及对肿瘤细胞选择性并能跨膜输送至细胞内达到有效浓度已成为肿瘤治疗的新的挑战。我们提出了利用纳米药物输送系统既实现肿瘤组织的靶向渗透性又实现肿瘤细胞内的靶向富集，为临床治疗肿瘤提供新的有效手段和策略。

　　提出了肿瘤免疫治疗的新方案：治疗性肿瘤疫苗通过使用肿瘤抗原刺激患者自身的免疫系统，使之产生杀伤肿瘤细胞的免疫反应，对抗甚至清除手术及放化疗后体内残存的肿瘤病灶和转移肿瘤。与传统治疗方法相比，肿瘤的免疫治疗具有特异性、长效性、低毒副作用等特点。大量的研究结果显示，纳米载体可通过多种机制的协同作用增强肿瘤抗原所诱发的免疫反应，纳米技术的发展为肿瘤治疗性疫苗的设计提供了全新的策略和方案。

1. Wang J, Xing X, Fang X, Zhou C, Huang F, Wu Z, Lou J,Liang W.Cationic amphiphilic drugs self-assemble to the core-shell interface of PEGylated phospholipid micelles and stabilize micellar structure.Philos Trans A Math PhysEng Sci.2013, 371(2000):20120309.

2. Qin L, Zhang F, Lu X, Wei X, Wang J, Fang X, Si D, Wang Y, Zhang C, Yang R, Liu C,Liang W.Polymeric micelles for enhanced lymphatic drug delivery to treat metastatic tumors.J Control Release.2013, 171(2):133-42.

3. Zhang M, Mao X, Wang C, Zeng W, Zhang C, Li Z, Fang Y, Yang Y,Liang W, Wang C. The effect of graphene oxide on conformation change aggregation and cytotoxicity of HIV-1 regultion protein.Biomaterials.2013, 34(4): 1383-90.

4. Yan Y, Zeng W, Song S, Zhang F, He W,Liang W,Niu Z. Vitamin C induces periodontal ligament progenitor cell differentiation via activation of ERK pathway mediated by PELP1.Protein Cell,2013, 4(8): 620–627.

5. Zeng W, Yan Y, Zhang F, Zhang C,Liang W.Chrysin promotes osteogenic differentiation via ERK/MAPK activation.Protein Cell, 2013. 4(7): 539–547

6. Zhang F, Shan L, Liu Y, Neville D, Woo JH, Chen Y, Korotcov A, Lin S, Huang S, Sridhar R,Liang W,Wang PC. An anti-PSMA bivalent immunotoxin exhibits specificity and efficacy for prostate cancer imaging and therapy.AdvHealthc Mater.2013 May; 2(5):736-44.

7. 张发云，秦蕾，梁伟. 活体自发光成像监测长春瑞宾胶束抗乳腺癌转移机制研究。中国肿瘤临床， 2013 ,40 ,23

8. 魏秀莉，梁伟. 聚乙二醇化磷脂胶束的纳米结构与功能.Progress in Biochemistry and Biophysics. 2013, 40(10): ~7.

9. Yi C, Zhang L, Li L, Liu X, Ling S, Zhang F,Liang W.Establishment of an orthotopicransplantation tumor model in nude mice using a drug-resistant human ovarian cancer cell line with a high expression of c-Kit.Oncol Lett.2014, 8(6):2611-2615.

10. Yi C, Zhang L, Zhang F, Li L, Ling S, Wang X, Liu X,Liang W.Methodologies for the establishment of an orthotopic transplantation model of ovarian cancer in mice.Front Med.2014, 8(1):101-5.

11. Dong W, Wei X, Zhang F, Hao J, Huang F, Zhang C,Liang W.A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways.Sci Rep.2014, 4:7237.

12. Zhou Y, Zhang C,Liang W.Development of RNAi technology for targeted therapy--a track of siRNA based agents to RNAi therapeutics.J Control Release.2014, 193:270-81.

13. Yu J, Wei X, Zhang L, Fang X, Yang T, Huang F,Liang W.Poly(ethylene glycol)-mediated conformational alteration of α-chymotrypsin prevents inactivation of insulin by stabilizing active intermediates.Mol Pharm.2014, 11(10):3361-70.

14. Han Z, Wang X, Heng C, Han Q, Cai S, Li J, Qi C,Liang W, Yang R, Wang C. Synergistically enhanced photocatalytic and chemotherapeutic effects of aptamer-functionalized ZnO nanoparticles towards cancer cells.PhysChemChem Phys.2015, 17(33):21576-82.

15. Fang X, Yang T, Wang L, Yu J, Wei X, Zhou Y, Wang C,Liang W.Nano-cage-mediated refolding of insulin by PEG-PE micelle.Biomaterials.2016, 77:139-48.

16. Meng J, Guo F, Xu H,Liang W, Wang C, Yang XD. Combination Therapy using Co-encapsulated Resveratrol and Paclitaxel in Liposomes for Drug Resistance Reversal in Breast Cancer Cells in vivo.Sci Rep.2016, 6:22390.

17. Li N, Yang Y, He K, Zhang F, Zhao L, Zhou W, Yuan J,Liang W, Fang X. Single-Molecule Imaging Reveals the Activation Dynamics of Intracellular Protein Smad3 on Cell Membrane.Sci Rep.2016, 6:33469.

18. Tang H, Wang Y, Chlewicki LK, Zhang Y, Guo J,Liang W, Wang J, Wang X, Fu YX. Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade.Cancer Cell.2016, 30(3):500.

19. Zhang F, Dong W, Zeng W, Zhang L, Zhang C, Qiu Y, Wang L, Yin X, Zhang C,Liang W. Naringenin prevents TGF-β1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation.Breast Cancer Res.2016, 18 (1):38.

20. Yinjian Zhou, Ying Dong , Gang Huang，Yiguang Wang，Xiaonan Huang, Fayun Zhang, David A. Boothman, JinmingGao,Wei Liang. Lysosome-Oriented, Dual Stages pH-Responsive Polymeric Micelles for β-Lapachone Delivery.Journal of Material Chemistry B.2016,4, 7429-7440

21. Zhida Liu, Chang Zhou, Yan Qin, Zihao Wang, Luyao Wang, Xiuli Wei, Yinjian Zhou, Qicheng Li, Hang Zhou, Wenjun Wang, Yang-Xin Fu, Mingzhao Zhu &Wei Liang. Coordinating antigen cytosolic delivery and danger signaling to program potent cross priming by micelle-based nanovaccine. 2017Cell Discovery(Accepted).

专      利：

1.梁伟，董文娟，张春玲，魏秀莉，黄峰. 一种以MAPK家族蛋白为靶标筛选调节病毒活性化合物的方法. CN103667420A.

2.梁伟，董文娟, 张春玲, 魏秀莉, 黄峰.人类免疫缺陷病毒抑制剂或药物增敏剂的筛选方法（授权）. CN103877595A.

3.梁伟，张春玲,曾文峰,张超,王洛洋.柚皮素和柚皮苷在肿瘤放射治疗中的应. CN104940932A.

4.梁伟，周畅，秦焱. 聚乙二醇化磷脂为载体的胶束多肽疫苗 (PCT). CN105194663A.

5.梁伟，刘志达，周畅，秦焱，朱明昭. 聚乙二醇化磷脂为载体的胶束多肽疫苗. CN104288758A.

6. 魏秀莉，于继兵，梁伟. 胰岛素结晶微球、其混悬剂、以及制备方法(授权). CN102397535A.

7. 魏秀莉，于继兵，梁伟. 一种新型的聚乙二醇化磷脂包载胰岛素的口服胶束制剂. CN103784400A.

8.WEI LIANG; GANGJUN DU; HONGYAN ZHANG; LINGTAO JIN; HEPING LU; WEI WANG; JINPING LIU; ZHEN FAN .Naringneinand naringin as signal pathway inhibitor of transforming growth factor-beta 1. EP2163247.

9.WEI LIANG; GANGJUN DU; HONGYAN ZHANG; LINGTAO JIN; HEPING LU; WEI WANG; JINPING LIU; ZHEN FAN .Naringneinand naringin as signal pathway inhibitor of transforming growth factor-beta 1. JP5484320.

（资料来源：梁伟研究员，2017-02-16）