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Chuan Wu

Chuan Wu, M.D., Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Senior Investigator
Experimental Immunology Branch

RESEARCH SUMMARY

It has become increasingly evident that interactions between the enteric nervous system (ENS) and the immune system play important roles to modulate inflammatory responses. Such interaction is particularly critical in the context of the intestinal microenvironment given the unique properties of this organ: intestinal tissue is continuously exposed to numerous microbial and food-derived antigens. In order to deal with these stimuli yet maintain normal physiology and function, intestinal responses are tightly regulated by actions of both the immune and nervous systems, which co-localize in the intestinal microenvironment with close proximity. Our lab mainly studies the role of intestinal neuroimmune interactions in health and disease. Understanding the cellular and molecular mechanisms of the dynamic interplay between the ENS and the immune system is critical for retrieving a comprehensive view of intestinal homeostasis and for discovering new therapeutics for intestinal inflammatory diseases, such as inflammatory bowel disease (IBD).

Areas of Expertise

T Cell Differentiation and Function
Inflammation
Neuron-Immune Interaction
Mucosal Immune Response
Epithelial Biology

Publications

Selected Recent Publications

Gut-liver axis calibrates intestinal stem cell fitness

Girak Kim, Zuojia Chen, Jian Li, Jialie Luo, Felipe Castro-Martinez, Jan Wisniewski, Kairong Cui, Yan Wang, Jialei Sun, Xiaobai Ren, Susan E. Crawford, S. Patricia Becerra, Jimin Zhu, Taotao Liu, Sui Wang, Keji Zhao, Chuan Wu
Cell. 2024.
Full-Text Article
[ Journal Article ]

Lipids regulate peripheral serotonin release via gut CD1d

Jialie Luo, Zuojia Chen, David Castellano, Bin Bao, Wenyan Han, Jian Li, Girak Kim, Dingding An, Wei Lu, Chuan Wu
Immunity. 2023.
Full-Text Article
[ Journal Article ]

Mucus sialylation determines intestinal host-commensal homeostasis

Yikun Yao, Girak Kim, Samantha Shafer, Zuojia Chen, Satoshi Kubo, Yanlong Ji, Jialie Luo, Weiming Yang, Sebastian P. Perner, Chrysi Kanellopoulou, Ann Y. Park, Ping Jiang, Jian Li, Safa Baris, Elif Karakoc Aydiner, Deniz Ertem, Daniel J. Mulder, Neil Warner, Anne M. Griffiths, Chani Topf-Olivestone, Michal Kori, Lael Werner, Jodie Ouahed, Michael Field, Chengyu Liu, Benjamin Schwarz, Catharine M. Bosio, Sundar Ganesan, Jian Song, Henning Urlaub, Thomas Oellerich, Stacy A. Malaker, Lixin Zheng, Carolyn R. Bertozzi, Yu Zhang, Helen Matthews, Will Montgomery, Han-Yu Shih, Jiansheng Jiang, Marcus Jones, Aris Baras, Alan Shuldiner, Claudia Gonzaga-Jauregui, Scott Snapper, Aleixo M. Muise, Dror S. Shouval, Ahmet Ozen, Kuan-Ting Pan, Chuan Wu*, Michael J. Lenardo*. *Corresponding author
Cell. 185(7): 1172-1188.e28, 2022.
Full-Text Article
[ Journal Article ]

Intestinal IL-33 promotes platelet activity for neutrophil recruitment during acute inflammation

Zuojia Chen, Jialie Luo, Jian Li, Girak Kim, Andrew Stewart, Yuefeng Huang, Chuan Wu
Blood. 139(12): 1878-1891, 2021.
Full-Text Article
[ Journal Article ]

Interleukin-33 promotes serotonin release from enterochromaffin cells for intestinal homeostasis

Zuojia Chen, Jialie Luo, Jian Li, Girak Kim, Andy Stewart, Joseph F Urban Jr, Yuefeng Huang, Shan Chen, Ling-Gang Wu, Alexander Chesler, Giorgio Trinchieri, Wei Li, Chuan Wu
Immunity. 54: 151-163.e6, 2021.
Full-Text Article
[ Journal Article ]

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Covers

Immunity Cover - May 9, 2023

Restraint of IFN-γ expression through a distal silencer CNS–28 for tissue homeostasis

Published Date

We report the identification of a negative regulatory element (CNS–28) that restrains IFNγ expression to ensure tissue homeostasis. CNS–28 forms a local 3D domain with two other regulatory elements, CNS–22 and CNS–34, in a manner dependent on the transcription factors MLL4 and GATA3; this structure prevents activation of Ifng transcription by the CNS–22 enhancer. The positive and negative mechanisms regulating expression of IFNg is depicted by the Taiji figure. Ifng genomic DNA (red ribbon) is embedded within repressive 3D chromatin (Yin; flower in the dark side) and activating 3D chromatin (Yang; flower in the light side). Illustration by Qinglan Emily Yu at the Bryn Mawr School.

Citation

https://www.cell.com/immunity/fulltext/S1074-7613(23)00126-7

Cell, Volume 185, Issue 7, p1105-1260

Mucus sialylation determines intestinal host-commensal homeostasis

Published Date

Sialylation is critical for intestinal mucus formation. Yao et al. (1172–1188) show that a local sialyltransferase in the gut, ST6GALNAC1 (ST6), determines mucin protein sialylation, protecting mucus barrier integrity from bacterial degradation. ST6-mediated mucus homeostasis in turn controls commensalism to establish intestinal host-microbial symbiosis. ST6 deficiency disrupts this mutualism, enhancing susceptibility to intestinal inflammation. The cover image illustrates that sialylated mucin proteins (saguaros with thorns) harbor symbiotic commensal bacteria (gilded flickers), protecting the intestinal tissue from pathogens (snakes and hawks). Loss of sialylation (saguaros without thorns) results in pathogenic bacteria invasion (snakes). Illustration concept by Chuan Wu and artwork by Alan Hoofring.

Citation

https://www.cell.com/cell/fulltext/S0092-8674(22)00193-3

Immunity Cover - August 21, 2014

Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells

Published Date

Galectin-9 can dampen autoimmune responses, and this process is associated with an increase in the frequency of inducible regulatory T (iTreg) cells. We show that galectin-9 potentiates the signal transduction of transforming growth factor βR (TGF-βR), a critical receptor for iTreg cell differentiation. Potentiation results in increased activation of Smad3 with subsequent enhanced transcription of the iTreg cell differentiation factor, FoxP3. The cover image illustrates T lymphocytes emerging from a microenvironment (represented by a fabricator) influenced by the presence of TGF-β. With assistance from galectin-9 and its receptor CD44, the differentiation process to iTreg cells is enhanced. Image by Chuan Wu.

Citation

http://www.sciencedirect.com/science/article/pii/S1074761314002325