Research Interests:
As the population ages, demand for effective medicines is rising. With the extensive exploration of druggable target with small molecular drugs, it has been increasingly difficult for drug discovery over the last 20 years. Meanwhile, the under-explored macromolecular therapeutic regime offers tremendous chances for innovative medicine discoveries. Currently, more and more biologics have been approved, with a considerable portion to tackle with diseases that are not easily treatable with current small-molecule approach. Despite the rapid growth in macromolecular therapeutics, intrinsic challenges still restrict their prospect.
Dr. Du's lab aims to solve the critical challenges in developing macromolecular therapeutics, thereby creating innovative biologic drugs. Du Lab's research lies in a highly interdisciplinary area, that largely relies on successful integration of multiple knowledge branches and skillsets, such as molecular biology, synthetic chemistry, protein engineering and bioconjugation technique. The research in Du lab is rooted in basic biology and synthetic chemistry. The overarching goal, on the other hand, is the conversion of scientific discovery into health improvement. Current projects include bench-to-bedside development of protein-based drugs for treatments as cancer, autoimmune diseases, diabetes, etc. In particular, Du Lab focuses on the following research areas to create next-generation therapeutics:
(1) To incorporate synthetic ligand into antibody CDR loops for novel therapeutic antibodies.
The traditional monoclonal antibodies cannot satisfy the ever-growing need for novel therapeutic antibodies. Especially, affinity-based antibody maturation process is not capable of generating antibodies with special functionalities, such as agonists, inverse-agonists and channel blockers. In Du Group, we are introducing the diversity of synthetic chemistry into the antigen binding residues to create novel functional antibodies.
(2) To improve the ability of biomacromolecules to penetrate plasma membrane by mimicking virus endocytosis process.
Many important disease-associated therapeutic targets are intracellular, including mutated genes and malfunctioning proteins. However, due to the protection by the plasma membrane, these therapeutic targets are barely accessible to macromolecular drugs. By mimicking the most efficient intracellular macromolecule delivery agent, virus, Du lab is currently establishing a strategy to facilitate the transport of biopharmaceuticals through plasma membrane. In the future, her lab will extend the strategy to antibody drug conjugate (ADC) and nucleic acid drugs.
(3) To develop multi-functional antibody therapeutics.
Next-generation antibody (NGA) therapeutics with antibody architecture modifications represent a key area of antibody research and development (R&D). Their rapid growth in the pharmaceutical market is expected in the next decade. Among them, multi-functional antibodies provide a unique platform to harness drug synergy and to discover novel mechanism of action (MOA). In Du Lab, we are exploring the therapeutic applications of novel multi-functional antibodies.
Scientific Contributions:
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Developed a general platform to encapsulate individual protein with polymer network, yielding nanocapsules with high stability, long circulation time and tunable surface functions.
Figure 1. Schematic illustration of the synthesis of protein nanocapsules and the morphology, stability, circulation time and surface function engineering of nanocapsules.
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Developed degradable nanocapsules for the sustained release of growth factors for tissue regeneration.
Figure 2. Degradable BMP-2 nanocapsules for bone regeneration with sustained release of BMP-2 and better therapeutic
outcome
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Invented novel antibody fusion strategy for therapeutic applications, such as tumor targeting bispecific antibody and switchable CAR-T therapy.
Figure 3: Bispecific antibody and CAR-T switch made by constant region fusion.
Honors and Awards
1000-Talents Plan for Young Researchers (2016)
Graduate Student Silver Award, Material Research Society (MRS) Spring Meeting (2013)
Dissertation Year Fellowship, University of California, Los Angeles (2012)
Selected Publications:
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.
Selected Patents:
1. Y. Lu; M. Yan; J. Du. Single protein nanocapsules for protein delivery with long-term effect. (WO 2010/104865 A3)
2. F. Wang; Y. Zhang; T. Liu; J. Du; Y. Wang; P. G. Schultz. Immunoglobulin fusion proteins and compositions thereof. (WO 2015/006744 A1)
3. F. Wang; J. Du; T. Young; P. G. Schultz. Constant region antibody fusion proteins and compositions thereof. (WO 2015/188135 A1)
