Full Text Journal Articles by
Author Cliff Guy


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Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions.

Jana L Raynor, Chaohong Liu, Yogesh Dhungana, Cliff Guy, Nicole M Chapman, Hao Shi, Geoffrey Neale, Hiromi Sesaki, Hongbo Chi,

Invariant natural killer T (iNKT) cells acquire effector functions during development by mechanisms that remain poorly understood. Here, we show that the Hippo kinases Mst1 and Mst2 act as molecular rheostats for the terminal maturation and effector differentiation programs of iNKT cells. Loss of Mst1 alone or together with Mst2 ... Read more >>

J. Exp. Med. (The Journal of experimental medicine)
[2020, 217(6):]

Cited: 0 times

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Mevalonate metabolism-dependent protein geranylgeranylation regulates thymocyte egress.

Xingrong Du, Hu Zeng, Shaofeng Liu, Cliff Guy, Yogesh Dhungana, Geoffrey Neale, Martin O Bergo, Hongbo Chi,

Thymocyte egress is a critical determinant of T cell homeostasis and adaptive immunity. Despite the roles of G protein-coupled receptors in thymocyte emigration, the downstream signaling mechanism remains poorly defined. Here, we report the discrete roles for the two branches of mevalonate metabolism-fueled protein prenylation pathway in thymocyte egress and ... Read more >>

J. Exp. Med. (The Journal of experimental medicine)
[2020, 217(2):]

Cited: 0 times

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Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy.

Jun Wei, Lingyun Long, Wenting Zheng, Yogesh Dhungana, Seon Ah Lim, Cliff Guy, Yanyan Wang, Yong-Dong Wang, Chenxi Qian, Beisi Xu, Anil Kc, Jordy Saravia, Hongling Huang, Jiyang Yu, John G Doench, Terrence L Geiger, Hongbo Chi,

Adoptive cell therapy represents a new paradigm in cancer immunotherapy, but it can be limited by the poor persistence and function of transferred T cells1. Here we use an in vivo pooled CRISPR-Cas9 mutagenesis screening approach to demonstrate that, by targeting REGNASE-1, CD8+ T cells are reprogrammed to long-lived effector ... Read more >>

Nature (Nature)
[2019, 576(7787):471-476]

Cited: 1 time

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Amino Acids License Kinase mTORC1 Activity and Treg Cell Function via Small G Proteins Rag and Rheb.

Hao Shi, Nicole M Chapman, Jing Wen, Cliff Guy, Lingyun Long, Yogesh Dhungana, Sherri Rankin, Stephane Pelletier, Peter Vogel, Hong Wang, Junmin Peng, Kun-Liang Guan, Hongbo Chi,

Regulatory T (Treg) cells are critical mediators of immune tolerance whose activity depends upon T cell receptor (TCR) and mTORC1 kinase signaling, but the mechanisms that dictate functional activation of these pathways are incompletely understood. Here, we showed that amino acids license Treg cell function by priming and sustaining TCR-induced mTORC1 ... Read more >>

Immunity (Immunity)
[2019, 51(6):1012-1027.e7]

Cited: 1 time

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Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis.

Jeeba Kuriakose, Vanessa Redecke, Cliff Guy, Jingran Zhou, Ruiqiong Wu, Sirish K Ippagunta, Heather Tillman, Patrick D Walker, Peter Vogel, Hans Häcker,

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with genetic and environmental contributions. Hallmarks of the disease are the appearance of immune complexes (IC) containing autoreactive Abs and TLR-activating nucleic acids, whose deposition in kidney glomeruli is suspected to promote tissue injury and glomerulonephritis (GN). Here, using a mouse ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2019, 129(6):2251-2265]

Cited: 1 time

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Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R-STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity.

Hao Shi, Chaohong Liu, Haiyan Tan, Yuxin Li, Thanh-Long M Nguyen, Yogesh Dhungana, Cliff Guy, Peter Vogel, Geoffrey Neale, Sherri Rankin, Yongqiang Feng, Junmin Peng, Wufan Tao, Hongbo Chi,

Interleukin-2 (IL-2) and downstream transcription factor STAT5 are important for maintaining regulatory T (Treg) cell homeostasis and function. Treg cells can respond to low IL-2 levels, but the mechanisms of STAT5 activation during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Mst1 as a signal-dependent amplifier of IL-2-STAT5 activity ... Read more >>

Immunity (Immunity)
[2018, 49(5):899-914.e6]

Cited: 2 times

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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis.

Dan E McNamara, Giovanni Quarato, Cliff S Guy, Douglas R Green, Tudor Moldoveanu,

Necroptosis is a programmed cell death pathway triggered by activation of receptor interacting protein kinase 3 (RIPK3), which phosphorylates and activates the mixed lineage kinase-like domain pseudokinase, MLKL, to rupture or permeabilize the plasma membrane. Necroptosis is an inflammatory pathway associated with multiple pathologies including autoimmunity, infectious and cardiovascular diseases, ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2018, (138):]

Cited: 0 times

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Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions.

Ashley V Menk, Nicole E Scharping, Rebecca S Moreci, Xue Zeng, Cliff Guy, Sonia Salvatore, Heekyong Bae, Jianxin Xie, Howard A Young, Stacy Gelhaus Wendell, Greg M Delgoffe,

To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, ... Read more >>

Cell Rep (Cell Reports)
[2018, 22(6):1509-1521]

Cited: 26 times

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PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development.

Mei Yu, Yuhong Chen, Hu Zeng, Yongwei Zheng, Guoping Fu, Wen Zhu, Ulrich Broeckel, Praful Aggarwal, Amy Turner, Geoffrey Neale, Cliff Guy, Nan Zhu, Hongbo Chi, Renren Wen, Demin Wang,

The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell development at the pre-pro-B ... Read more >>

Nat Commun (Nature communications)
[2017, 8(1):1457]

Cited: 3 times

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Biological events and molecular signaling following MLKL activation during necroptosis.

Yi-Nan Gong, Cliff Guy, Jeremy Chase Crawford, Douglas R Green,

Necroptosis is a form of programmed necrotic cell death mediated by the kinase RIPK3 and its substrate MLKL. MLKL, which displays plasma membrane (PM) pore-forming activity upon phosphorylation, functions as the executioner during necroptosis. Thus, it was previously assumed that MLKL phosphorylation is the endpoint of the necroptotic signaling pathway. Here, ... Read more >>

Cell Cycle (Cell cycle (Georgetown, Tex.))
[2017, 16(19):1748-1760]

Cited: 10 times

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Critical roles of mTORC1 signaling and metabolic reprogramming for M-CSF-mediated myelopoiesis.

Peer W F Karmaus, Andrés A Herrada, Cliff Guy, Geoffrey Neale, Yogesh Dhungana, Lingyun Long, Peter Vogel, Julian Avila, Clary B Clish, Hongbo Chi,

Myelopoiesis is necessary for the generation of mature myeloid cells during homeostatic turnover and immunological insults; however, the metabolic requirements for this process remain poorly defined. Here, we demonstrate that myelopoiesis, including monocyte and macrophage differentiation, requires mechanistic target of rapamycin complex 1 (mTORC1) signaling and anabolic metabolism. Loss of ... Read more >>

J. Exp. Med. (The Journal of experimental medicine)
[2017, 214(9):2629-2647]

Cited: 10 times

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ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences.

Yi-Nan Gong, Cliff Guy, Hannes Olauson, Jan Ulrich Becker, Mao Yang, Patrick Fitzgerald, Andreas Linkermann, Douglas R Green,

The activation of mixed lineage kinase-like (MLKL) by receptor-interacting protein kinase-3 (RIPK3) results in plasma membrane (PM) disruption and a form of regulated necrosis, called necroptosis. Here, we show that, during necroptosis, MLKL-dependent calcium (Ca2+) influx and phosphatidylserine (PS) exposure on the outer leaflet of the plasma membrane preceded loss of ... Read more >>

Cell (Cell)
[2017, 169(2):286-300.e16]

Cited: 90 times

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Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation.

Haiyan Tan, Kai Yang, Yuxin Li, Timothy I Shaw, Yanyan Wang, Daniel Bastardo Blanco, Xusheng Wang, Ji-Hoon Cho, Hong Wang, Sherri Rankin, Cliff Guy, Junmin Peng, Hongbo Chi,

The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell ... Read more >>

Immunity (Immunity)
[2017, 46(3):488-503]

Cited: 41 times

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Corrigendum: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells.

Jennifer Martinez, Larissa D Cunha, Sunmin Park, Mao Yang, Qun Lu, Robert Orchard, Quan-Zhen Li, Mei Yan, Laura Janke, Cliff Guy, Andreas Linkermann, Herbert W Virgin, Douglas R Green,

Nature (Nature)
[2016, 539(7627):124]

Cited: 2 times

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mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.

Hu Zeng, Sivan Cohen, Cliff Guy, Sharad Shrestha, Geoffrey Neale, Scott A Brown, Caryn Cloer, Rigel J Kishton, Xia Gao, Ben Youngblood, Mytrang Do, Ming O Li, Jason W Locasale, Jeffrey C Rathmell, Hongbo Chi,

Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and ... Read more >>

Immunity (Immunity)
[2016, 45(3):540-554]

Cited: 76 times

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Sequential Engagement of Distinct MLKL Phosphatidylinositol-Binding Sites Executes Necroptosis.

Giovanni Quarato, Cliff S Guy, Christy R Grace, Fabien Llambi, Amanda Nourse, Diego A Rodriguez, Randall Wakefield, Sharon Frase, Tudor Moldoveanu, Douglas R Green,

Necroptosis is a cell death pathway regulated by the receptor interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) pseudokinase. How MLKL executes plasma membrane rupture upon phosphorylation by RIPK3 remains controversial. Here, we characterize the hierarchical transduction of structural changes in MLKL that culminate in necroptosis. ... Read more >>

Mol. Cell (Molecular cell)
[2016, 61(4):589-601]

Cited: 50 times

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Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis.

Jun Wei, Lingyun Long, Kai Yang, Cliff Guy, Sharad Shrestha, Zuojia Chen, Chuan Wu, Peter Vogel, Geoffrey Neale, Douglas R Green, Hongbo Chi,

Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of Treg cells is maintained under activating environments is unclear. Here we show that autophagy is active in Treg cells and supports their lineage stability and survival fitness. Treg cell-specific deletion of ... Read more >>

Nat. Immunol. (Nature immunology)
[2016, 17(3):277-285]

Cited: 96 times

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Metabolic maintenance of cell asymmetry following division in activated T lymphocytes.

Katherine C Verbist, Cliff S Guy, Sandra Milasta, Swantje Liedmann, Marcin M Kamiński, Ruoning Wang, Douglas R Green,

Asymmetric cell division, the partitioning of cellular components in response to polarizing cues during mitosis, has roles in differentiation and development. It is important for the self-renewal of fertilized zygotes in Caenorhabditis elegans and neuroblasts in Drosophila, and in the development of mammalian nervous and digestive systems. T lymphocytes, upon ... Read more >>

Nature (Nature)
[2016, 532(7599):389-393]

Cited: 79 times

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Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses.

Sharad Shrestha, Kai Yang, Cliff Guy, Peter Vogel, Geoffrey Neale, Hongbo Chi,

The interplay between effector T cells and regulatory T cells (Treg cells) is crucial for adaptive immunity, but how Treg cells control diverse effector responses is elusive. We found that the phosphatase PTEN links Treg cell stability to repression of type 1 helper T cell (TH1 cell) and follicular helper ... Read more >>

Nat. Immunol. (Nature immunology)
[2015, 16(2):178-187]

Cited: 143 times

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Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis.

Greg M Delgoffe, Seng-Ryong Woo, Meghan E Turnis, David M Gravano, Cliff Guy, Abigail E Overacre, Matthew L Bettini, Peter Vogel, David Finkelstein, Jody Bonnevier, Creg J Workman, Dario A A Vignali,

Regulatory T cells (Treg cells) have a crucial role in the immune system by preventing autoimmunity, limiting immunopathology, and maintaining immune homeostasis. However, they also represent a major barrier to effective anti-tumour immunity and sterilizing immunity to chronic viral infections. The transcription factor Foxp3 has a major role in the ... Read more >>

Nature (Nature)
[2013, 501(7466):252-256]

Cited: 209 times

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IL-35-mediated induction of a potent regulatory T cell population.

Lauren W Collison, Vandana Chaturvedi, Abigail L Henderson, Paul R Giacomin, Cliff Guy, Jaishree Bankoti, David Finkelstein, Karen Forbes, Creg J Workman, Scott A Brown, Jerold E Rehg, Michael L Jones, Hsiao-Tzu Ni, David Artis, Mary Jo Turk, Dario A A Vignali,

Regulatory T cells (T(reg) cells) have a critical role in the maintenance of immunological self-tolerance. Here we show that treatment of naive human or mouse T cells with IL-35 induced a regulatory population, which we call 'iT(R)35 cells', that mediated suppression via IL-35 but not via the inhibitory cytokines IL-10 ... Read more >>

Nat. Immunol. (Nature immunology)
[2010, 11(12):1093-1101]

Cited: 349 times

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Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development.

Haopeng Wang, Jeff Holst, Seng-Ryong Woo, Cliff Guy, Matt Bettini, Yao Wang, Aaron Shafer, Mayumi Naramura, Michaël Mingueneau, Leonard L Dragone, Sandra M Hayes, Bernard Malissen, Hamid Band, Dario A A Vignali,

Expression of the T-cell receptor (TCR):CD3 complex is tightly regulated during T-cell development. The mechanism and physiological role of this regulation are unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not mature single positive (SP) thymocytes or splenic T cells. ... Read more >>

EMBO J. (The EMBO journal)
[2010, 29(7):1285-1298]

Cited: 27 times

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'Sustainable transport choices' in consumer shopping: a review of the UK evidence

Cliff Guy,

In the UK, as elsewhere in Europe, government policy aims to reduce the use of private cars for consumer shopping trips. One major instrument of policy aims to ensure that new retail development is located in places accessible by all transport modes. This paper reviews the effectiveness of this and ... Read more >>

(International journal of consumer studies.)
[2009, 33(6):652-658]

Cited: 1 time

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Analysis of nondegradative protein ubiquitylation with a monoclonal antibody specific for lysine-63-linked polyubiquitin.

Haopeng Wang, Atsushi Matsuzawa, Scott A Brown, JingRan Zhou, Cliff S Guy, Ping-Hui Tseng, Karen Forbes, Thomas P Nicholson, Paul W Sheppard, Hans Häcker, Michael Karin, Dario A A Vignali,

Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. However, identifying such modifications in living cells is complex and cumbersome. We have generated a monoclonal antibody (mAb) ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2008, 105(51):20197-20202]

Cited: 38 times

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