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  1. Article ; Online: Wendell Lim: exploring the path not chosen. Interview by Caitlin Sedwick.

    Lim, Wendell

    The Journal of cell biology

    2012  Volume 198, Issue 6, Page(s) 956–957

    MeSH term(s) Evolution, Molecular ; Humans ; Protein Structure, Tertiary ; Proteins/genetics ; Proteins/metabolism ; Signal Transduction
    Chemical Substances Proteins
    Language English
    Publishing date 2012-09-18
    Publishing country United States
    Document type Interview
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.1986pi
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: From folding towards function.

    Baker, David / Lim, Wendell A

    Current opinion in structural biology

    2023  Volume 12, Issue 1, Page(s) 11–13

    Language English
    Publishing date 2023-05-10
    Publishing country England
    Document type Editorial
    ZDB-ID 1068353-7
    ISSN 1879-033X ; 0959-440X
    ISSN (online) 1879-033X
    ISSN 0959-440X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Golden age of immunoengineering.

    Wong, Wilson W / Lim, Wendell A

    Immunological reviews

    2023  Volume 320, Issue 1, Page(s) 4–9

    MeSH term(s) Humans ; Immunotherapy ; Neoplasms ; Immunotherapy, Adoptive
    Language English
    Publishing date 2023-10-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13283
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The emerging era of cell engineering: Harnessing the modularity of cells to program complex biological function.

    Lim, Wendell A

    Science (New York, N.Y.)

    2022  Volume 378, Issue 6622, Page(s) 848–852

    Abstract: A new era of biological engineering is emerging in which living cells are used as building blocks to address therapeutic challenges. These efforts are distinct from traditional molecular engineering-their focus is not on optimizing individual genes and ... ...

    Abstract A new era of biological engineering is emerging in which living cells are used as building blocks to address therapeutic challenges. These efforts are distinct from traditional molecular engineering-their focus is not on optimizing individual genes and proteins as therapeutics, but rather on using molecular components as modules to reprogram how cells make decisions and communicate to achieve higher-order physiological functions in vivo. This cell-centric approach is enabled by a growing tool kit of components that can synthetically control core cell-level functional outputs, such as where in the body a cell should go, what other cells it should interact with, and what messages it should transmit or receive. The power of cell engineering has been clinically validated by the development of immune cells designed to kill cancer. This same tool kit for rewiring cell connectivity is beginning to be used to engineer cell therapies for a host of other diseases and to program the self-organization of tissues and organs. By forcing the conceptual distillation of complex biological functions into a finite set of instructions that operate at the cell level, these efforts also shed light on the fundamental hierarchical logic that links molecular components to higher-order physiological function.
    MeSH term(s) Humans ; Cell Engineering ; Neoplasms/therapy ; Cell- and Tissue-Based Therapy/methods ; Immunotherapy, Adoptive/methods ; T-Lymphocytes/immunology ; T-Lymphocytes/transplantation
    Language English
    Publishing date 2022-11-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.add9665
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Rethinking cancer targeting strategies in the era of smart cell therapeutics.

    Allen, Greg M / Lim, Wendell A

    Nature reviews. Cancer

    2022  Volume 22, Issue 12, Page(s) 693–702

    Abstract: In the past several decades, the development of cancer therapeutics has largely focused on precision targeting of single cancer-associated molecules. Despite great advances, such targeted therapies still show incomplete precision and the eventual ... ...

    Abstract In the past several decades, the development of cancer therapeutics has largely focused on precision targeting of single cancer-associated molecules. Despite great advances, such targeted therapies still show incomplete precision and the eventual development of resistance due to target heterogeneity or mutation. However, the recent development of cell-based therapies such as chimeric antigen receptor (CAR) T cells presents a revolutionary opportunity to reframe strategies for targeting cancers. Immune cells equipped with synthetic circuits are essentially living computers that can be programmed to recognize tumours based on multiple signals, including both tumour cell-intrinsic and microenvironmental. Moreover, cells can be programmed to launch broad but highly localized therapeutic responses that can limit the potential for escape while still maintaining high precision. Although these emerging smart cell engineering capabilities have yet to be fully implemented in the clinic, we argue here that they will become much more powerful when combined with machine learning analysis of genomic data, which can guide the design of therapeutic recognition programs that are the most discriminatory and actionable. The merging of cancer analytics and synthetic biology could lead to nuanced paradigms of tumour recognition, more akin to facial recognition, that have the ability to more effectively address the complex challenges of treating cancer.
    MeSH term(s) Humans ; Neoplasms/genetics ; Immunotherapy, Adoptive ; Cell Engineering ; Synthetic Biology
    Language English
    Publishing date 2022-09-29
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/s41568-022-00505-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Engineering cytokines and cytokine circuits.

    Li, Aileen W / Lim, Wendell A

    Science (New York, N.Y.)

    2020  Volume 370, Issue 6520, Page(s) 1034–1035

    MeSH term(s) Cell Engineering ; Cytotoxicity, Immunologic ; Humans ; Immunotherapy/methods ; Interferon-alpha/therapeutic use ; Interleukin-2/therapeutic use ; Protein Engineering ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Interferon-alpha ; Interleukin-2
    Language English
    Publishing date 2020-11-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abb5607
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Harnessing synthetic biology to engineer organoids and tissues.

    Trentesaux, Coralie / Yamada, Toshimichi / Klein, Ophir D / Lim, Wendell A

    Cell stem cell

    2022  Volume 30, Issue 1, Page(s) 10–19

    Abstract: The development of an organism depends on intrinsic genetic programs of progenitor cells and their spatiotemporally complex extrinsic environment. Ex vivo generation of organoids from progenitor cells provides a platform for recapitulating and exploring ... ...

    Abstract The development of an organism depends on intrinsic genetic programs of progenitor cells and their spatiotemporally complex extrinsic environment. Ex vivo generation of organoids from progenitor cells provides a platform for recapitulating and exploring development. Current approaches rely largely on soluble morphogens or engineered biomaterials to manipulate the physical environment, but the emerging field of synthetic biology provides a powerful toolbox to genetically manipulate cell communication, adhesion, and even cell fate. Applying these modular tools to organoids should lead to a deeper understanding of developmental principles, improved organoid models, and an enhanced capability to design tissues for regenerative purposes.
    MeSH term(s) Synthetic Biology ; Organoids ; Biocompatible Materials ; Stem Cells ; Cell Differentiation
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2022-12-31
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2022.12.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Degron-based bioPROTACs for controlling signaling in CAR T cells.

    Kim, Matthew S / Bhargava, Hersh K / Shavey, Gavin E / Lim, Wendell A / El-Samad, Hana / Ng, Andrew H

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Chimeric antigen receptor (CAR) T cells have made a tremendous impact in the clinic, but potent signaling through the CAR can be detrimental to treatment safety and efficacy. The use of protein degradation to control CAR signaling can address these ... ...

    Abstract Chimeric antigen receptor (CAR) T cells have made a tremendous impact in the clinic, but potent signaling through the CAR can be detrimental to treatment safety and efficacy. The use of protein degradation to control CAR signaling can address these issues in pre-clinical models. Existing strategies for regulating CAR stability rely on small molecules to induce systemic degradation. In contrast to small molecule regulation, genetic circuits offer a more precise method to control CAR signaling in an autonomous, cell-by-cell fashion. Here, we describe a programmable protein degradation tool that adopts the framework of bioPROTACs, heterobifunctional proteins that are composed of a target recognition domain fused to a domain that recruits the endogenous ubiquitin proteasome system. We develop novel bioPROTACs that utilize a compact four residue degron and demonstrate degradation of cytosolic and membrane protein targets using either a nanobody or synthetic leucine zipper as a protein binder. Our bioPROTACs exhibit potent degradation of CARs and can inhibit CAR signaling in primary human T cells. We demonstrate the utility of our bioPROTACs by constructing a genetic circuit to degrade the tyrosine kinase ZAP70 in response to recognition of a specific membrane-bound antigen. This circuit is able to disrupt CAR T cell signaling only in the presence of a specific cell population. These results suggest that bioPROTACs are a powerful tool for expanding the cell engineering toolbox for CAR T cells.
    Language English
    Publishing date 2024-02-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.16.580396
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: High-throughput multicolor optogenetics in microwell plates.

    Bugaj, Lukasz J / Lim, Wendell A

    Nature protocols

    2019  Volume 14, Issue 7, Page(s) 2205–2228

    Abstract: Optogenetic probes can be powerful tools for dissecting complexity in cell biology, but there is a lack of instrumentation to exploit their potential for automated, high-information-content experiments. This protocol describes the construction and use of ...

    Abstract Optogenetic probes can be powerful tools for dissecting complexity in cell biology, but there is a lack of instrumentation to exploit their potential for automated, high-information-content experiments. This protocol describes the construction and use of the optoPlate-96, a platform for high-throughput three-color optogenetics experiments that allows simultaneous manipulation of common red- and blue-light-sensitive optogenetic probes. The optoPlate-96 enables illumination of individual wells in 96-well microwell plates or in groups of wells in 384-well plates. Its design ensures that there will be no cross-illumination between microwells in 96-well plates, and an active cooling system minimizes sample heating during light-intensive experiments. This protocol details the steps to assemble, test, and use the optoPlate-96. The device can be fully assembled without specialized equipment beyond a 3D printer and a laser cutter, starting from open-source design files and commercially available components. We then describe how to perform a typical optogenetics experiment using the optoPlate-96 to stimulate adherent mammalian cells. Although optoPlate-96 experiments are compatible with any plate-based readout, we describe analysis using quantitative single-cell immunofluorescence. This workflow thus allows complex optogenetics experiments (independent control of stimulation colors, intensity, dynamics, and time points) with high-dimensional outputs at single-cell resolution. Starting from 3D-printed and laser-cut components, assembly and testing of the optoPlate-96 can be accomplished in 3-4 h, at a cost of ~$600. A full optoPlate-96 experiment with immunofluorescence analysis can be performed within ~24 h, but this estimate is variable depending on the cell type and experimental parameters.
    MeSH term(s) Animals ; Cell Culture Techniques ; Color ; Equipment Design ; Lasers ; Mice ; NIH 3T3 Cells ; Optogenetics/instrumentation ; Optogenetics/methods ; Phytochrome B/chemistry ; Printing, Three-Dimensional
    Chemical Substances Phytochrome B (136250-22-1)
    Language English
    Publishing date 2019-06-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2244966-8
    ISSN 1750-2799 ; 1754-2189
    ISSN (online) 1750-2799
    ISSN 1754-2189
    DOI 10.1038/s41596-019-0178-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Building a Stable Relationship: Ensuring Homeostasis among Cell Types within a Tissue.

    Frankel, Nicholas W / Lim, Wendell A

    Cell

    2018  Volume 172, Issue 4, Page(s) 638–640

    Abstract: Many processes controlling cell growth and death are well characterized for individual cell lineages, but how ensembles of different cell types in a tissue regulate collective size and composition remains unclear. In this issue of Cell, Zhou et al. ... ...

    Abstract Many processes controlling cell growth and death are well characterized for individual cell lineages, but how ensembles of different cell types in a tissue regulate collective size and composition remains unclear. In this issue of Cell, Zhou et al. employ experiments and theory to uncover design principles of tissue homeostasis arising from cross-talk between fibroblasts and macrophages.
    MeSH term(s) Cell Lineage ; Cell Physiological Phenomena ; Fibroblasts ; Homeostasis ; Macrophages
    Language English
    Publishing date 2018-02-20
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.01.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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