随着人口老龄化的加剧，整个社会对更有效的药物治疗的需求随之上升。然而，随着制药行业对于小分子药物可成药的靶向目标的不断筛选，发现新的靶向目标也越来越难。同时，大分子药物、尤其是蛋白质药物的崛起为新药的开发提供了巨大的机会。目前，越来越多的大分子药物已被批准，其中有相当一部分治疗的正是目前小分子药物无法治疗的疾病。然而，与其迅速的增长相比，一些内在的挑战仍然限制大分子药物的发展前景。本实验室的研究致力于解决大分子药物研发过程中的一些关键性的挑战，从而研制出创新性的生物类药物。本实验室的研究处于交叉学科的领域，其很大程度上依赖于对于各种知识和技能的综合，如分子生物学、化学合成、蛋白质工程和生物偶联技术。本实验室的工作根植于基础的生物和化学知识；从而实现由科学发现向临床应用的转化。目前的科研项目包含“从实验到临床”的药物研究，主要集中在采用蛋白为基础的新一代大分子药物治疗癌症、免疫系统疾病、糖尿病等等。具体而言，本实验室主要致力于以下几个方面的研究：
。传统的单克隆抗体研发已无法满足现今对于新型抗体药物不断增长的需求。并且，以结合强度为准则的抗体筛选方法无法产生有特定功能的抗体药物，比如具有激动剂或反激动剂活性的抗体、或者离子通道阻滞剂及酶抑制剂。本课题组利用合成化学的多样性，大大拓展了传统抗体在抗原识别区对于有限的20种天然氨基酸官能团的依赖，以简单普适的方法获得新型的功能性抗体。
。很多重要的药物靶点都存在于细胞内部，其中包括携带突变的基因和功能错误的蛋白。尽管蛋白质、DNA和RNA可以有效的作用于细胞内的药物靶点并调节其功能，但是细胞膜阻止了大分子药物对这类药物靶点的接触，从而使大分子药物不能发挥其在细胞内的作用。本实验室模仿自然界中最有效的大分子胞内传递系统——病毒，设计了有效的组织特异性胞内蛋白传递系统。借由此系统，也可以实现有效的小分子药物及核酸类药物的胞内传递。
。下一代抗体药物（NGA）是以抗体修饰为基本的新型药物类型。在未来十年内，NGA被预测会得到长足的发展并在抗体药物的市场上占到举足轻重的地位。其中，多功能性抗体可以利用药物之间的协同作用，也可以开发新的治疗机理，更是为新型抗体药物的开发提供了一个广阔的平台。本实验室采用蛋白融合、特异性偶联等技术开发多种多功能性抗体。
发明了以单个蛋白质为内核、生物相容性的高分子为外壳的蛋白－高分子纳米复合体（单蛋白纳米胶囊），并以此提高了蛋白的稳定性，延长了蛋白的循环时间以及实现了可控的表面功能性。
优秀研究生银奖, 美国材料学会(MRS)，2013年
研究生论文奖, 加州大学洛杉矶分校，2012年
代表论文
1. H. Tian†; J. Du† (Co-author with equal contribution); J. Wen; Y. Liu; S. R. Montgomery; T. P. Scott; B. Aghdasi; C. Xiong; A. Suzuki; T. Hayashi; M. Ruangchainikom; K. Phan; G. Weintraub; A. Raed; S. S. Murray; M. D. Daubs; X. Yang; X.-B. Yuan; J. C. Wang; Y. Lu. Growth-Factor Nanocapsules That Enable Tunable Controlled Release for Bone Regeneration. ACS Nano 2016 in press
2. T. Liu†; J. Du† (Co-author with equal contribution); X. Luo; P. G. Schultz; F. Wang. Homogeneously modified immunoglobulin domains for therapeutic application. Curr. Opin. Chem. Biol. 2015, 28, 66-74.
3. J. Du; J. Jin; Y. Liu; J. Li; T. Tokatlian; Z. Lu; T. Segura; X. Yuan; X. Yang; Y. Lu. Gold-Nanocrystal Enhanced Bioluminescent Nanocapsules. ACS Nano, 2014, 8, 9964-9969.
4. W. Wei†; J. Du† (Co-author with equal contribution); J. Li; M. Yan; Q. Zhu; X. Jin; X. Zhu; Z. Hu; Y. Tang; Y. Lu. Construction of Robust Enzyme Nanocapsules for Effective Organophosphate Decontamination, Detoxification and Protection. Advanced Materials, 2013, 25, 2212-2218.
5. Y. Liu†; J. Du† (Co-author with equal contribution); M. Yan; M. Y. Lau; J. Hu ; H. Han ; O. O. Yang ; S. Liang ; W. Wei ; H. Wang ; J. Li ; X. Zhu ; L. Shi; W. Chen ; C. Ji; Y. Lu. Biomimetic Enzyme Nanocomplexes and Their Use as Antidotes and Preventive Measures for Alcohol Intoxication. Nature Nanotechnology, 2013, 8, 187-192.
6. J. Du; J. Jin; M. Yan; Y. Lu. Synthetic Nanocarriers for Intracellular Protein Delivery. Current Drug Metabolism, 2012, 13, 82-92.
7. J. Du; C. Yu; D. Pan ; J. Li; W. Chen; M. Yan; T. Segura; Y. Lu. Quantum-Dot-Decorated Robust Transductable Bioluminescent Nanocapsules. J. Am. Chem. Soc. 2010, 132, 12780-12781.
8. M. Yan†; J. Du† (Co-author with equal contribution); Z. Gu; M. Liang; Y. Hu; W. Zhang; S. Priceman; L. Wu; Z. H. Zhou; Z. Liu; T. Segura; Y. Tang; Y. Lu. A novel intracellular protein delivery platform based on single-protein nanocapsules. Nature Nanotechnology, 2010, 5, 48-53.
9. J. Du; Z. Li; D.-M. Du; J. Xu. Improving enantioselectivity via rationally tuning electronic effects of catalysts in organocatalytic asymmetric Aldo reaction. ARKIVOC, 2008, 17, 145-156.
10. J. Du; Z. Li; D.-M. Du; J. Xu. Unexpected influence and its origin in rationally tuning the electronic effect of catalysts in the asymmetric borane reduction of ketones. J. Mol. Cat. A: Chemical, 2008, 284, 40-45.
11. Y. Cao; D. T. Rodgers; J. Du; I. Ahmad; E. N. Hampton; J. S. Y. Ma; M. Mazagova; S.-H. Choi; H. Y. Yun; H. Xiao; P. Yang; X. Luo; R. K. V. Lim; H. M. Pugh; F. Wang; S. A. Kazane; T. M. Wright; C. H. Kim; P. G. Schultz; T. S. Young. Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer. Angew. Chem. Int. Ed. 2016, in press
12. Y. Liu; J. Du; J.-S. Choi; K.-J. Chen; S. Hou; M. Yan; W.-Y. Lin; K. S. Chen; T. Ro; G. S. Lipshutz; L. Wu; L. Shi; Y. Lu; H.-R. Tseng; H. Wang. A High-Throughput Platform for Formulating and Screening Multifunctional Nanoparticles Capable of Simultaneous Delivery of Genes and Transcription Factors. Angew. Chem. Int. Ed. 2016, 55, 169–173.
13. D. T. Rodgers; M. Mazagova; E. N. Hampton; Y. Cao; N. S. Ramadoss; I. R. Hardy; A. Schulman; J. Du; F. Wang; O. Singer; J. Ma; V. Nunez; J. Shen; A. K. Woods; T. M. Wright; P. G. Schultz; C. H. Kim; T. S. Young. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc. Nat. Acad. Sci. 2016, 113, E459–E468
14. X. Luo; T. Liu; Y. Wang; H. Jia; Y. Zhang; D. Caballero; J. Du; R. E. Wang; D. Wang; P. G. Schultz; F. Wang. An Epitope-Specific Respiratory Syncytial Virus Vaccine Based on an Antibody Scaffold. Angew. Chem. Int. Ed. 2015, 54, 14531–14534.
15. J. Wen; S. M. Anderson; J. Du; M. Yan; J. Wang; M. Shen; Y. Lu; T. Segura. Controlled Protein Delivery Based on Enzyme-Responsive Nanocapsules, Advance Materials, 2011, 23, 4549-4553.
16. J. Zhang; Y. Lei; A. Dhaliwal; Q. K. Ng; J. Du; M. Yan; Y. Lu; T. Segura. Protein-Polymer Nanoparticles for Nonviral Gene Delivery, Biomacromolecules, 2011, 12, 1006-1014.
17. J. Zhang; J. Du; M. Yan; A. Dhaliwal; J. Wen; F. Liu; T. Segura; Y. Lu. Synthesis of Protein Nano-Conjugates for Cancer Therapy. Nano Res., 2011, 4, 425-433.
18. Y. Peng; D. Jiang; L. Su; L. Zhang; M. Yan; J. Du; Y. Lu; Y. Liu; F. Zhou. Mixed Monolayers of Ferrocenylalkanethiol and Encapsulated Horseradish Peroxidase for Sensitive and Durable Electrochemical Detection of Hydrogen Peroxide, Anal. Chem., 2009, 81, 9985-9992.
19. X. Wang; J. Du; H. Liu; D.-M. Du; J. Xu. Effect of borane source on the enantioselectivity in the enantiopure oxazaborolidine-catalyzed asymmetric borane reduction of ketones. Hetero. Chem., 2007, 18, 740-746.
专利申请
Y. Lu; M. Yan; J. Du. Single protein nanocapsules for protein delivery with long-term effect. (WO 2010/104865 A3)
F. Wang; Y. Zhang; T. Liu; J. Du; Y. Wang; P. G. Schultz. Immunoglobulin fusion proteins and compositions thereof. (WO 2015/006744 A1)
F. Wang; J. Du; T. Young; P. G. Schultz. Constant region antibody fusion proteins and compositions thereof. (WO 2015/188135 A1)
