Chuan Wu, M.D., Ph.D.
Experimental Immunology Branch
Building 10, Room 4B17
Bethesda, MD 20892-1360
1. Cytokine regulation of intestinal peristalsis
The neuroimmune interactions involve the actions of neurotransmitters, neuromodulators, and cytokines that carry signals, often bidirectionally, between enteric neurons and immune cells. Such dynamic interactions within the intestinal environment have profound consequences for gastrointestinal (GI) secretion and motility. Power propulsive motility is a recognizable component of an intestinal defense program and immunoneural communication activates the program. We will study how cytokines integrate in neural regulation on GI motility during intestinal homeostasis and inflammation.
2. Reciprocal regulation of colonic Treg cell (cTreg) and enteric neuron.
During central nervous system (CNS) inflammation, neurons are highly immune-regulatory governing T cell response. These modulations can be achieved via neuropeptides, which are received by neuropeptide receptors expressed on T cells. However, it is not clear whether similar interactions occur within GI compartment. Intestinal inflammation causes multiple changes in the intrinsic tissue motor circuits, including neuronal hyperexcitability and increased synaptic facilitation. It is known that enteric innervation contributes to the pathogenesis of intestinal bowel disease (IBD). On the other hand, cTreg cells are also reported to be critical modulators during intestinal inflammation. To establish the cooperative interactions between cTreg cells and the enteric neurons, both of which rapidly produce tissue-protective responses, will provide new therapeutic strategies for the treatment of IBD and irritable bowel syndrome (IBS).
3. Human ENS lineages for cell therapy and drug discovery in humanized colitis model.
In order to further develop therapeutic approaches to modify human neural and immune dysfunctions during intestinal inflammation, we will establish a humanized animal model which hosts either human T cells or the ENS or both.
Dr. Wu completed his M.D. at Shanghai Jiaotong University, School of Medicine. He undertook his doctoral research training at Muenster University, Germany, focusing on T cell migration during inflammation and autoimmunity. In 2010, he started his post-doctoral training at Brigham and Women’s Hospital, Harvard Medical School, where he studied transcriptional regulation for T cell differentiation. During his postdoctoral period, he was awarded the K99 NIH Award and National Multiple Sclerosis Society Career Transition Award. He was also the recipient of the Regeneron Creative Innovation Award. In 2016, Dr. Wu joined the faculty at Brigham and Women’s Hospital as an Assistant Professor and then moved to NCI in 2017 as an Earl Stadtman Investigator, where he re-directed his research to focus on how neuro-immune crosstalk regulates mucosal homeostasis. Throughout his career, Dr. Wu has published many peer-reviewed manuscripts and review articles. His career aspirations are to understand the mechanisms of how neuro-immune interactions contribute to body physiology and pathophysiology, and to facilitate the development of new therapies for immune-mediated diseases.
Chen Z, Luo J, Li J, Kim G, Stewart A, Urban JF Jr, Huang Y, Chen S, Wu LG, Chesler A, Trinchieri G, Li W, Wu C. Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis. Immunity. 2020.
Lai NY, Musser MA, Pinho-Ribeiro FA, Baral P, Jacobson A, Ma P, Potts DE, Chen Z, Paik D, Soualhi S, Yan Y, Misra A, Goldstein K, Lagomarsino VN, Nordstrom A, Sivanathan KN, Wallrapp A, Kuchroo VK, Nowarski R, Starnbach MN, Shi H, Surana NK, An D, Wu C, Huh JR, Rao M, Chiu IM. Gut-Innervating Nociceptor Neurons Regulate Peyer's Patch Microfold Cells and SFB Levels to Mediate Salmonella Host Defense. Cell. 2020;180(1):33-49.e22.
Lin F, Meng X, Guo Y, Cao W, Liu W, Xia Q, Hui Z, Chen J, Hong S, Zhang X, Wu C, Wang D, Wang J, Lu L, Qian W, Wei L, Wang L. Epigenetic initiation of the TH17 differentiation program is promoted by Cxxc finger protein 1. Sci Adv. 2019;5(10):eaax1608.
Biton M, Haber AL, Rogel N, Burgin G, Beyaz S, Schnell A, Ashenberg O, Su CW, Smillie C, Shekhar K, Chen Z, Wu C, Ordovas-Montanes J, Alvarez D, Herbst RH, Zhang M, Tirosh I, Dionne D, Nguyen LT, Xifaras ME, Shalek AK, von Andrian UH, Graham DB, Rozenblatt-Rosen O, Shi HN, Kuchroo V, Yilmaz OH, Regev A, Xavier RJ. T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation. Cell. 2018;175(5):1307-1320.e22.
Wu C, Chen Z, Xiao S, Thalhamer T, Madi A, Han T, Kuchroo V. SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells. Cell Rep. 2018;22(3):653-665.
Related Scientific Focus Areas
Microbiology and Infectious Diseases
Molecular Biology and Biochemistry
This page was last updated on April 19th, 2021