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  1. Article ; Online: CaSSiDI: novel single-cell "Cluster Similarity Scoring and Distinction Index" reveals critical functions for PirB and context-dependent Cebpb repression.

    Nechanitzky, Robert / Ramachandran, Parameswaran / Nechanitzky, Duygu / Li, Wanda Y / Wakeham, Andrew C / Haight, Jillian / Saunders, Mary E / Epelman, Slava / Mak, Tak W

    Cell death and differentiation

    2024  Volume 31, Issue 3, Page(s) 265–279

    Abstract: PirB is an inhibitory cell surface receptor particularly prominent on myeloid cells. PirB curtails the phenotypes of activated macrophages during inflammation or tumorigenesis, but its functions in macrophage homeostasis are obscure. To elucidate PirB- ... ...

    Abstract PirB is an inhibitory cell surface receptor particularly prominent on myeloid cells. PirB curtails the phenotypes of activated macrophages during inflammation or tumorigenesis, but its functions in macrophage homeostasis are obscure. To elucidate PirB-related functions in macrophages at steady-state, we generated and compared single-cell RNA-sequencing (scRNAseq) datasets obtained from myeloid cell subsets of wild type (WT) and PirB-deficient knockout (PirB KO) mice. To facilitate this analysis, we developed a novel approach to clustering parameter optimization called "Cluster Similarity Scoring and Distinction Index" (CaSSiDI). We demonstrate that CaSSiDI is an adaptable computational framework that facilitates tandem analysis of two scRNAseq datasets by optimizing clustering parameters. We further show that CaSSiDI offers more advantages than a standard Seurat analysis because it allows direct comparison of two or more independently clustered datasets, thereby alleviating the need for batch-correction while identifying the most similar and different clusters. Using CaSSiDI, we found that PirB is a novel regulator of Cebpb expression that controls the generation of Ly6C
    MeSH term(s) Animals ; Mice ; Macrophages/metabolism ; Monocytes/metabolism ; Myeloid Cells/metabolism ; Receptors, Cell Surface ; Receptors, Immunologic/metabolism ; Single-Cell Analysis/methods ; CCAAT-Enhancer-Binding Protein-beta/metabolism
    Chemical Substances Receptors, Cell Surface ; Receptors, Immunologic ; Pirb protein, mouse ; Cebpb protein, mouse ; CCAAT-Enhancer-Binding Protein-beta
    Language English
    Publishing date 2024-02-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-024-01268-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book: The immune response

    Mak, Tak W. / Saunders, Mary E.

    basic and clinical principles

    2006  

    Author's details Tak W. Mak and Mary E. Saunders
    Keywords Immune System ; Immunity ; Immune System Diseases ; Immunreaktion
    Subject Abwehrreaktion ; Immunantwort ; Immunoreaktivität ; Immunabwehr
    Language English
    Size XX, 1194 S. : Ill., graph. Darst.
    Publisher Elsevier, Acad. Press
    Publishing place Amsterdam u.a.
    Publishing country Netherlands
    Document type Book
    Note Systemvoraussetzungen CD-ROM-Beil.: Windows: Windows 98, 2000, ME, or XP; Pentium II processor; 233 MHz or higher; 64 MB of available RAM; 2 MB of available hard-disk space; 8x or faster CD-ROM drive; VGA monitor supporting 256 colors; 800 x 600 screen resolution; Internet Explorer 5.0 or later. - Macintosh: Apple PowerPC 166 MHz or higher; Mac OS version 10.2 or higher; 64 MB of available RAM; 2 MB of available hard-disk space; 8x or faster CD-ROM drive; VGA monitor supporting 256 colors; 800 x 600 screen resolution; Netscape 4.76 or later
    Accompanying material 1 CD-ROM (12 cm)
    HBZ-ID HT014363670
    ISBN 978-0-12-088451-3 ; 978-0-12-369532-1 ; 0-12-088451-8 ; 0-12-369532-5
    Database Catalogue ZB MED Medicine, Health

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  3. Article ; Online: Beyond the Oncogene Revolution: Four New Ways to Combat Cancer.

    Berger, Thorsten / Saunders, Mary E / Mak, Tak W

    Cold Spring Harbor symposia on quantitative biology

    2016  Volume 81, Page(s) 85–92

    Abstract: It has become clear that tumorigenesis results from much more than just the activation of an oncogene and/or the inactivation of a tumor-suppressor gene, and that the cancer cell genome contains many more alterations than can be specifically targeted at ... ...

    Abstract It has become clear that tumorigenesis results from much more than just the activation of an oncogene and/or the inactivation of a tumor-suppressor gene, and that the cancer cell genome contains many more alterations than can be specifically targeted at once. This observation has led our group to a search for alternative ways to kill cancer cells (while sparing normal cells) by focusing on properties unique to the former. We have identified four approaches with the potential to generate new anticancer therapies: combatting the tactics by which cancers evade antitumor immune responses, targeting metabolic adaptations that tumor cells use to survive conditions that would kill normal cells, manipulating a cancer cell's response to excessive oxidative stress, and exploiting aneuploidy. This review describes our progress to date on these fronts.
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ISSN 1943-4456 ; 0091-7451
    ISSN (online) 1943-4456
    ISSN 0091-7451
    DOI 10.1101/sqb.2016.81.031161
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Dissection of signaling in inflammation: three novel inflammatory regulators.

    Berger, Thorsten / Saunders, Mary E / Mak, Tak W

    Cold Spring Harbor symposia on quantitative biology

    2013  Volume 78, Page(s) 141–147

    Abstract: Uncontrolled inflammation is a feature of autoimmune diseases and autoinflammatory syndromes and may promote tumorigenesis. Thus, identifying molecules that regulate the signaling pathways triggering, mediating, and suppressing inflammation could be ... ...

    Abstract Uncontrolled inflammation is a feature of autoimmune diseases and autoinflammatory syndromes and may promote tumorigenesis. Thus, identifying molecules that regulate the signaling pathways triggering, mediating, and suppressing inflammation could be helpful in developing new therapeutic approaches for these debilitating diseases. In this review, we present new information on three molecules with important roles in controlling inflammation: MALT1, Ariadne-2, and acetylcholine. We summarize our current state of knowledge of how these molecules function, and how they are involved in pathways of NF-κB activation or vagal nerve stimulation associated with inflammation.
    MeSH term(s) Acetylcholine/metabolism ; Animals ; Anti-Inflammatory Agents/chemistry ; Autoimmune Diseases/metabolism ; Caspases/metabolism ; Computer Simulation ; Gene Expression Regulation ; Humans ; Inflammation ; Mice ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein ; NF-kappa B/metabolism ; Neoplasm Proteins/metabolism ; Phosphorylation ; Signal Transduction ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Anti-Inflammatory Agents ; NF-kappa B ; Neoplasm Proteins ; ARIH2 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Caspases (EC 3.4.22.-) ; MALT1 protein, human (EC 3.4.22.-) ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein (EC 3.4.22.-) ; Acetylcholine (N9YNS0M02X)
    Language English
    Publishing date 2013
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1943-4456 ; 0091-7451
    ISSN (online) 1943-4456
    ISSN 0091-7451
    DOI 10.1101/sqb.2013.78.020107
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis.

    Nechanitzky, Robert / Nechanitzky, Duygu / Ramachandran, Parameswaran / Duncan, Gordon S / Zheng, Chunxing / Göbl, Christoph / Gill, Kyle T / Haight, Jillian / Wakeham, Andrew C / Snow, Bryan E / Bradaschia-Correa, Vivian / Ganguly, Milan / Lu, Zhibin / Saunders, Mary E / Flavell, Richard A / Mak, Tak W

    Cell death and differentiation

    2022  Volume 30, Issue 2, Page(s) 407–416

    Abstract: Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS) in which Th17 cells have a crucial but unclear function. Here we show that choline acetyltransferase (ChAT), which synthesizes acetylcholine (ACh), is a critical ... ...

    Abstract Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS) in which Th17 cells have a crucial but unclear function. Here we show that choline acetyltransferase (ChAT), which synthesizes acetylcholine (ACh), is a critical driver of pathogenicity in EAE. Mice with ChAT-deficient Th17 cells resist disease progression and show reduced brain-infiltrating immune cells. ChAT expression in Th17 cells is linked to strong TCR signaling, expression of the transcription factor Bhlhe40, and increased Il2, Il17, Il22, and Il23r mRNA levels. ChAT expression in Th17 cells is independent of IL21r signaling but dampened by TGFβ, implicating ChAT in controlling the dichotomous nature of Th17 cells. Our study establishes a cholinergic program in which ACh signaling primes chronic activation of Th17 cells, and thereby constitutes a pathogenic determinant of EAE. Our work may point to novel targets for therapeutic immunomodulation in MS.
    MeSH term(s) Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental ; Th17 Cells ; Virulence ; Cholinergic Agents ; Multiple Sclerosis/genetics ; Acetylcholine/metabolism ; Mice, Inbred C57BL ; Cell Differentiation
    Chemical Substances Cholinergic Agents ; Acetylcholine (N9YNS0M02X)
    Language English
    Publishing date 2022-12-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-022-01092-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Tumor-specific cholinergic CD4

    Zheng, Chunxing / Snow, Bryan E / Elia, Andrew J / Nechanitzky, Robert / Dominguez-Brauer, Carmen / Liu, Shaofeng / Tong, Yin / Cox, Maureen A / Focaccia, Enrico / Wakeham, Andrew C / Haight, Jillian / Tobin, Chantal / Hodgson, Kelsey / Gill, Kyle T / Ma, Wei / Berger, Thorsten / Heikenwälder, Mathias / Saunders, Mary E / Fortin, Jerome /
    Leung, Suet Yi / Mak, Tak W

    Nature cancer

    2023  Volume 4, Issue 10, Page(s) 1437–1454

    Abstract: Cholinergic nerves are involved in tumor progression and dissemination. In contrast to other visceral tissues, cholinergic innervation in the hepatic parenchyma is poorly detected. It remains unclear whether there is any form of cholinergic regulation of ...

    Abstract Cholinergic nerves are involved in tumor progression and dissemination. In contrast to other visceral tissues, cholinergic innervation in the hepatic parenchyma is poorly detected. It remains unclear whether there is any form of cholinergic regulation of liver cancer. Here, we show that cholinergic T cells curtail the development of liver cancer by supporting antitumor immune responses. In a mouse multihit model of hepatocellular carcinoma (HCC), we observed activation of the adaptive immune response and induction of two populations of CD4
    MeSH term(s) Animals ; Mice ; Carcinoma, Hepatocellular/genetics ; Liver Neoplasms/genetics ; Programmed Cell Death 1 Receptor/genetics ; Monitoring, Immunologic ; T-Lymphocytes, Regulatory/pathology
    Chemical Substances Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2023-08-28
    Publishing country England
    Document type Journal Article
    ISSN 2662-1347
    ISSN (online) 2662-1347
    DOI 10.1038/s43018-023-00624-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book: The immune response

    Mak, Tak W / Saunders, Mary E

    basic and clinical principles

    2006  

    Author's details Tak W. Mak and Mary E. Saunders ; contributors, Maya R. Chaddah, Wendy L. Tamminen
    Keywords Immunology. ; Immunity.
    Language English
    Size xx, 1194 p. :, col. ill. ;, 29 cm. +
    Publisher Elsevier/Academic
    Publishing place Amsterdam ; Boston
    Document type Book
    Accompanying material 1 CD-ROM (4 3/4 in.)
    ISBN 0120884518 ; 0123695325 ; 9780120884513 ; 9780123695321
    Database NAL-Catalogue (AGRICOLA)

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  8. Book: The immune response

    Mak, Tak W / Saunders, Mary E

    basic and clinical principles

    2006  

    Author's details Tak W. Mak and Mary E. Saunders ; contributors, Maya R. Chaddah, Wendy L. Tamminen
    MeSH term(s) Immune System ; Immunity ; Immune System Diseases
    Language English
    Size xx, 1194 p. :, ill., ports. +
    Publisher Elsevier Academic Press
    Publishing place Burlington, Mass
    Document type Book
    Accompanying material 1 CD-ROM (4 3/4 in.).
    ISBN 9780120884513 ; 0120884518 ; 9780123695321 ; 0123695325
    Database Catalogue of the US National Library of Medicine (NLM)

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