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. studies in China at Shanghai Jiaotong University School of Medicine, and then studied immunology and matrix biology as a graduate student at Muenster University, Germany. His main focus was T cell migration during the central nervous system (CNS) inflammation. He joined Dr. Vijay Kuchroo’s lab in Brigham and Women’s Hospital, Harvard Medical School as a postdoctoral fellow where he studied the molecular regulation of T cell differentiation during inflammation and autoimmunity. In 2017, Dr. Wu started a position as an NIH Stadtman Tenure-Track Investigator at the Experimental Immunology Branch where he studies the cellular and molecular mechanisms of neuro-immune interactions.
Wu C, Chen Z, Dardalhon V, Xiao S, Thalhamer T, Liao M, Madi A, Franca RF, Han T, Oukka M, Kuchroo V. The transcription factor musculin promotes the unidirectional development of peripheral T<sub>reg</sub> cells by suppressing the T<sub>H</sub>2 transcriptional program. Nat Immunol. 2017;18(3):344-353.
Wu C, Thalhamer T, Franca RF, Xiao S, Wang C, Hotta C, Zhu C, Hirashima M, Anderson AC, Kuchroo VK. Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells. Immunity. 2014;41(2):270-82.
Wu C, Pot C, Apetoh L, Thalhamer T, Zhu B, Murugaiyan G, Xiao S, Lee Y, Rangachari M, Yosef N, Kuchroo VK. Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation. Proc Natl Acad Sci U S A. 2013;110(19):7802-7.
Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, Regev A, Kuchroo VK. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature. 2013;496(7446):513-7.
Wu C, Ivars F, Anderson P, Hallmann R, Vestweber D, Nilsson P, Robenek H, Tryggvason K, Song J, Korpos E, Loser K, Beissert S, Georges-Labouesse E, Sorokin LM. Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med. 2009;15(5):519-27.
Related Scientific Focus Areas
Microbiology and Infectious Diseases
Molecular Biology and Biochemistry
This page was last updated on February 4th, 2019