Chen, Yvonne - University of California, Berkeley

个人简介

B.S., Chemical Engineering, Stanford University Ph.D., Chemical Engineering, California Institute of Technology Yvonne earned her B.S. in Chemical Engineering from Stanford University and her Ph.D. in Chemical Engineering from the California Institute of Technology. She received postdoctoral training at the Center for Childhood Cancer Research within the Seattle Children’s Research Institute, and at the Department of Systems Biology at Harvard Medical School. Yvonne was a Junior Fellow in the Harvard Society of Fellows prior to joining the Department of Chemical and Biomolecular Engineering at the University of California, Los Angeles in 2013. Dr. Chen has been a recipient of the NIH Director’s Early Independence Award, the ACGT Young Investigator Award in Cell and Gene Therapy for Cancer, the NSF CAREER Award, the Mark Foundation Emerging Leader Award, and the Cancer Research Institute’s Lloyd J. Old STAR Award. Yvonne is also a Member Researcher in the Parker Institute for Cancer Immunotherapy.

研究领域

Building Synthetic Biological Circuits for Medical Applications Synthetic biology—an emerging field that applies foundational technologies including high-throughput DNA synthesis, sequencing, and assembly to the construction of novel biological systems with programmed functionality—has generated numerous model systems capable of increasingly complex functions in recent years. Our laboratory is interested in applying synthetic biology expertise to the engineering of novel biological circuits with direct applications in health and medicine. Our focus is on mammalian systems, particularly in cell-based therapy for cancer. Current projects include rewiring cytokine-signaling pathways in T cells that can recognize the tumor microenvironment and, in response to tumor detection, simultaneously execute tumor-killing functions and recruit supporting immune responders to the tumor site. These novel systems aim to enhance the safety and efficacy of cell-based therapy to tackle currently incurable diseases. Engineering Next-Generation Chimeric Antigen Receptors Chimeric antigen receptors (CARs) are synthetic, fusion proteins composed of antibody-based extracellular domains linked to intracellular signaling domains typically derived from the natural T-cell receptor complex (e.g., CD3 zeta chain). CAR-modified T cells have shown exciting potential in treating otherwise intractable diseases such as relapsing leukemia and lymphoma, metastatic melanoma, and glioblastoma multiforme. State-of-the-art CARs are single-input, single-output devices that execute a killing function in response to the detection of one antigen signal. As a result, CAR-based therapies are vulnerable to off-target toxicity toward healthy cells as well as mutational escape by tumor cells. Our laboratory is developing next-generation CARs that can perform logical computation of multiple input signals, thereby increasing the specificity as well as versatility of CAR-modified T cells for cancer therapy.

近期论文

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Chang, Z.L., Hou, A.J., and Chen, Y.Y.Engineering primary T cells with chimeric antigen receptors for rewired responses to soluble ligands Nature Protocols. 2020 Chen, L.C. and Chen, Y.Y.Outsmarting and outmuscling cancer cells with synthetic and systems immunology Current Opinion in Biotechnology. 2019:111-118. Chen, Y.Y. and Van Deventer, J.A. Editorial overview: Pharmaceutical biotechnology: new frontiers in protein, gene, and cell therapies Current Opinion in Biotechnology. 2019:iii-v. Hou, A.J.*, Chang, Z.L.*, Lorenzini, M.H., Zah, E., and Chen, Y.Y.TGF-β–responsive CAR-T cells promote anti-tumor immune function Bioengineering and Translational Medicine. 2018:85-86. Chen, Y.Y.Preview: Increasing T-cell Versatility with SUPRA CARs Cell. 2018;173(6):1316-1317. Ho, P. and Chen, Y.Y.Synthetic Biology in Immunotherapy Wiley Biotechnology Series--Synthetic Biology: Parts, Devices, and Applications. 2018:849-372. Chang, Z.L., Lorenzini, M.H., Chen, X., Tran, U., Bangayan, N.J., and Chen, Y.Y.Rewiring T-cell responses to soluble factors with chimeric antigen receptors Nature Chemical Biology. 2018;14(3):317-324. Wong, R.S., Chen, Y.Y., and Smolke, C.D.Regulation of T cell proliferation with drug-responsive microRNA switches Nucleic Acids Research. 2018:1541-1552. Zah, E. and Chen, Y.Y.Engineering Cancer-Fighting T Cells Chemical Engineering Progress. 2017 Oct:40-46. Ho, P. and Chen, Y.Y.Mammalian synthetic biology in the age of genome editing and personalized medicine Current Opinion in Chemical Biology. 2017:57-64. Ho, P., Ede, C., and Chen, Y.Y.Modularly Constructed Synthetic Granzyme B Molecule Enables Interrogation of Intracellular Proteases for Targeted Cytotoxicity ACS Synthetic Biology. 2017;6(8):1484-1495. Chang, Z.L. and Chen, Y.Y.CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond Trends in Molecular Medicine. 2017;23(5):430-450. Zah, E., Lin, M.Y., Silva-Benedict, A., Jensen, M.C., Chen, Y.Y.ADDENDUM: T cells expressing CD19/CD20 bi-specific chimeric antigen receptors prevent antigen escape by malignant B cells Cancer Immunology Research. 2016;4(7):639-641. Zah, E., Lin, M.Y., Silva-Benedict, A., Jensen, M.C., Chen, Y.Y.T cells expressing CD19/CD20 bi-specific chimeric antigen receptors prevent antigen escape by malignant B cells Cancer Immunology Research. 2016;4(6):498-508. Ede, C., Chen, X., Lin, M.Y., Chen, Y.Y.Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells ACS Synthetic Biology. 2016;5(5):395-404. Chen, Y.Y.Efficient gene editing in primary human T cells Trends in Immunology. 2015;36(11):667-669. Chang, Z., Silver, P.A., Chen, Y.Y.Identification and selective expansion of functionally superior T cells expressing chimeric antigen receptors Journal of Translational Medicine. 2015;13(1):161. Wei, K.Y., Chen, Y.Y., Smolke, C.D.A yeast-based rapid prototype platform for gene-control elements in mammalian cells Biotechnology and Bioengineering. 2013;110(4):1201-10. Chen, Y.Y.*, Galloway, K.E.*, Smolke, C.D.Synthetic biology: Advancing biological frontiers by building synthetic systems Genome Biology. 2012;13(2):240. *These authors contributed equally. Chen, Y.Y. & Smolke, C.D.From DNA to targeted therapeutics: Bringing synthetic biology to the clinic Science Translational Medicine. 2011;3(106):106ps42.