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  1. Article ; Online: Distinguishing parallel from series circuits with a double knockdown procedure in human cell lines.

    Gocher-Demske, Angela M / Dai, Shuhang / Edelman, Arthur M

    STAR protocols

    2022  Volume 3, Issue 4, Page(s) 101890

    Abstract: Signaling cascades can act in series or in parallel. Here, we describe a convenient and robust protocol for dual, sequential knockdown of two proteins using RNA interference. We detail the steps for a quantitative mapping of signaling circuitry. We used ... ...

    Abstract Signaling cascades can act in series or in parallel. Here, we describe a convenient and robust protocol for dual, sequential knockdown of two proteins using RNA interference. We detail the steps for a quantitative mapping of signaling circuitry. We used this approach to study kinases in human ovarian cancer cells, but the protocol can be applied to many other posttranslational modifications. For complete details on the use and execution of this protocol, please refer to Gocher et al. (2017).
    MeSH term(s) Humans ; Female ; Cell Line ; Ovarian Neoplasms/genetics ; Protein Processing, Post-Translational ; RNA Interference ; Signal Transduction
    Language English
    Publishing date 2022-11-30
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101890
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Catch and release: freeing up PD-L1 ameliorates autoimmunity.

    Grebinoski, Stephanie / Gocher-Demske, Angela M / Vignali, Dario A A

    Nature immunology

    2022  Volume 23, Issue 3, Page(s) 344–346

    MeSH term(s) Autoimmunity/immunology ; B7-H1 Antigen/immunology ; Lymphocyte Activation ; Programmed Cell Death 1 Receptor/immunology ; T-Lymphocytes/immunology
    Chemical Substances B7-H1 Antigen ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2022-02-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-022-01140-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5294: Show issues Location:
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  3. Article ; Online: IFNγ-induction of T

    Gocher-Demske, Angela M / Cui, Jian / Szymczak-Workman, Andrea L / Vignali, Kate M / Latini, Julianna N / Pieklo, Gwen P / Kimball, Jesse C / Avery, Lyndsay / Cipolla, Ellyse M / Huckestein, Brydie R / Hedden, Lee / Meisel, Marlies / Alcorn, John F / Kane, Lawrence P / Workman, Creg J / Vignali, Dario A A

    Nature immunology

    2023  Volume 24, Issue 5, Page(s) 841–854

    Abstract: Regulatory T ( ... ...

    Abstract Regulatory T (T
    MeSH term(s) T-Lymphocytes, Regulatory ; Interferon-gamma/metabolism ; Cytokines/metabolism ; CD8-Positive T-Lymphocytes ; Antiviral Agents/metabolism ; Th1 Cells
    Chemical Substances Interferon-gamma (82115-62-6) ; Cytokines ; Antiviral Agents
    Language English
    Publishing date 2023-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01453-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Calcium/calmodulin-dependent protein kinase kinase 2 mediates pleiotropic effects of epidermal growth factor in cancer cells.

    Dai, Shuhang / Venturini, Elisa / Yadav, Saveg / Lin, Xiaoxuan / Clapp, Dylan / Steckiewicz, Martin / Gocher-Demske, Angela M / Hardie, D Grahame / Edelman, Arthur M

    Biochimica et biophysica acta. Molecular cell research

    2022  Volume 1869, Issue 7, Page(s) 119252

    Abstract: Aims: Engagement of epidermal growth factor (EGF) with its receptor (EGFR) produces a broad range of cancer phenotypes. The overriding aim of this study was to understand EGFR signaling and its regulation by the Ca: Results: In ovarian cancer cells ... ...

    Abstract Aims: Engagement of epidermal growth factor (EGF) with its receptor (EGFR) produces a broad range of cancer phenotypes. The overriding aim of this study was to understand EGFR signaling and its regulation by the Ca
    Results: In ovarian cancer cells and other cancer cell types, EGF-induced activation of oncogenic Akt is mediated by both the canonical PI3K-PDK1 pathway and by CaMKK2. Akt activation induced by EGF occurs by both calcium-dependent and calcium-independent mechanisms. In contrast to the canonical pathway, CaMKK2 neither binds to, nor is regulated by phosphoinositides but is activated by Ca
    Conclusions: CaMKK2-mediation of EGFR action may enable cancer cells to use intracellular calcium elevation as a signal for growth and survival.
    MeSH term(s) Calcium/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics ; Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism ; Epidermal Growth Factor/pharmacology ; ErbB Receptors/genetics ; Neoplasms ; Proto-Oncogene Proteins c-akt/genetics
    Chemical Substances Epidermal Growth Factor (62229-50-9) ; ErbB Receptors (EC 2.7.10.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Calcium-Calmodulin-Dependent Protein Kinase Kinase (EC 2.7.11.17) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2022-03-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2022.119252
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment.

    Bender, Mackenzie J / McPherson, Alex C / Phelps, Catherine M / Pandey, Surya P / Laughlin, Colin R / Shapira, Jake H / Medina Sanchez, Luzmariel / Rana, Mohit / Richie, Tanner G / Mims, Tahliyah S / Gocher-Demske, Angela M / Cervantes-Barragan, Luisa / Mullett, Steven J / Gelhaus, Stacy L / Bruno, Tullia C / Cannon, Nikki / McCulloch, John A / Vignali, Dario A A / Hinterleitner, Reinhard /
    Joglekar, Alok V / Pierre, Joseph F / Lee, Sonny T M / Davar, Diwakar / Zarour, Hassane M / Meisel, Marlies

    Cell

    2023  Volume 186, Issue 9, Page(s) 1846–1862.e26

    Abstract: The use of probiotics by cancer patients is increasing, including among those undergoing immune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-host crosstalk between probiotic-released aryl hydrocarbon receptor (AhR) ... ...

    Abstract The use of probiotics by cancer patients is increasing, including among those undergoing immune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-host crosstalk between probiotic-released aryl hydrocarbon receptor (AhR) agonist indole-3-aldehyde (I3A) and CD8 T cells within the tumor microenvironment that potently enhances antitumor immunity and facilitates ICI in preclinical melanoma. Our study reveals that probiotic Lactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its released dietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8 T cells, thereby bolstering ICI. Moreover, Lr-secreted I3A was both necessary and sufficient to drive antitumor immunity, and loss of AhR signaling within CD8 T cells abrogated Lr's antitumor effects. Further, a tryptophan-enriched diet potentiated both Lr- and ICI-induced antitumor immunity, dependent on CD8 T cell AhR signaling. Finally, we provide evidence for a potential role of I3A in promoting ICI efficacy and survival in advanced melanoma patients.
    MeSH term(s) Humans ; Diet ; Immune Checkpoint Inhibitors ; Limosilactobacillus reuteri/metabolism ; Melanoma/therapy ; Tryptophan/metabolism ; Tumor Microenvironment ; CD8-Positive T-Lymphocytes/immunology ; Receptors, Aryl Hydrocarbon/agonists
    Chemical Substances Immune Checkpoint Inhibitors ; Tryptophan (8DUH1N11BX) ; Receptors, Aryl Hydrocarbon
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2023.03.011
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