Youngsu C. Kwon

Discovery of Clinical Candidate GDC-8264, a Novel, Potent and Selective RIP1 Inhibitor for Amelioration of Tissue Damage and the Treatment of Inflammatory Diseases

Snahel D. Patel, Huifen Chen, Eugene E. Varfolomeev, Youngsu C. Kwon et autres

Abstract Receptor-interacting protein 1 (RIP1) is a critical regulator of inflammatory cell death induced by diverse stimuli including TNF family ligands and ischemic injury. As such, the inhibition of RIP1 with small molecule kinase inhibitors is predicted to ameliorate tissue damage and …

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Multiplexed proteomics of autophagy-deficient murine macrophages reveals enhanced antimicrobial immunity via the oxidative stress response

Timurs Maculins, Erik Verschueren, Trent B. Hinkle, Meena Choi et autres

Defective autophagy is strongly associated with chronic inflammation. Loss-of-function of the core autophagy gene Atg16l1 increases risk for Crohn’s disease in part by enhancing innate immunity through myeloid cells such as macrophages. However, autophagy is also recognized as a mechanism for clearance …

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Author response: Multiplexed proteomics of autophagy-deficient murine macrophages reveals enhanced antimicrobial immunity via the oxidative stress response

Timurs Maculins, Erik Verschueren, Trent B. Hinkle, Meena Choi et autres

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Integration of innate immune signalling by caspase-8 cleavage of N4BP1

Alexander D. Gitlin, Klaus Heger, Alexander F. Schubert, Rohit Reja et autres

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CD96 functions as a co‐stimulatory receptor to enhance CD8 + T cell activation and effector responses

Eugene Y. Chiang, Patricia E. de Almeida, Denise E. de Almeida Nagata, Kristin Harden Bowles et autres

Abstract CD96 is a member of the poliovirus receptor (PVR, CD155)‐nectin family that includes T cell Ig and ITIM domain (TIGIT) and CD226. While CD96, TIGIT, and CD226 have important roles in regulating NK cell activity, and TIGIT and CD226 have also …

RIP1 kinase activity is critical for skin inflammation but not for viral propagation

Joshua D. Webster, Youngsu C. Kwon, Summer Park, Hua Zhang et autres

Receptor interacting protein kinase 1 (RIP1) is a critical effector of inflammatory responses and cell death activation. Cell death pathways regulated by RIP1 include caspase-dependent apoptosis and caspase-independent necroptosis. The kinase activity of RIP1 has been associated with a number of inflammatory, …

Author response for "CD96 functions as a co‐stimulatory receptor to enhance CD8 + T cell activation and effector responses"

Eugene Y. Chiang, Patrícia E. de Almeida, Denise E. de Almeida Nagata, Kristin Harden Bowles et autres

RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases

Snahel D. Patel, Joshua D. Webster, Eugene E. Varfolomeev, Youngsu C. Kwon et autres

The kinase RIP1 acts in multiple signaling pathways to regulate inflammatory responses and it can trigger both apoptosis and necroptosis. Its kinase activity has been implicated in a range of inflammatory, neurodegenerative, and oncogenic diseases. Here, we explore the effect of inhibiting …

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Ubiquitin Ligases cIAP1 and cIAP2 Limit Cell Death to Prevent Inflammation

Jieqiong Zhang, Joshua D. Webster, Debra L. Dugger, Tatiana Goncharov et autres

Cellular inhibitor of apoptosis proteins cIAP1 and cIAP2 ubiquitinate nuclear factor κB (NF-κB)-inducing kinase (NIK) to suppress non-canonical NF-κB signaling and substrates such as receptor interacting protein kinase 1 (RIPK1) to promote cell survival. We investigate how these functions contribute to homeostasis …

Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma

Hart S. Dengler, Xiumin Wu, Ivan Peng, Cornelia H. Rinderknecht et autres

Preclinical and clinical evidence indicates that a subset of asthma is driven by type 2 cytokines such as interleukin-4 (IL-4), IL-5, IL-9, and IL-13. Additional evidence predicts pathogenic roles for IL-6 and type I and type II interferons. Because each of these …

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The Effect of Creating a Prior Event in Story Telling

Youngsu C. Kwon, Jungok Bae

This study investigated what effect the creation of a prior event has on content quality in story writing and if the effect varies depending on easy versus difficult topics. Two topics (overslept, digging) were selected; for each topic, two tasks (prior-required, prior-unrequired) …

Inflammatory Bowel Disease Susceptibility Gene C1ORF106 Regulates Intestinal Epithelial Permeability

Paolo S. Manzanillo, Maria L. Mouchess, Naruhisa Ota, Bingbing Dai et autres

Abstract Intestinal epithelial cells form a physical barrier that is tightly regulated to control intestinal permeability. Proinflammatory cytokines, such as TNF-α, increase epithelial permeability through disruption of epithelial junctions. The regulation of the epithelial barrier in inflammatory gastrointestinal disease remains to be …