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

Chuan Wu, M.D., Ph.D.
Stadtman Investigator

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. My research interest is to study 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 diseases (IBD).

Areas of Expertise

1) T cell differentiation and function, 2) inflammation, 3) neuron-immune interaction,
4) mucosal immune response

Contact Info

Chuan Wu, M.D., Ph.D.
Center for Cancer Research
National Cancer Institute
Building 10, Room 4B17
Bethesda, MD 20892-1360
Ph: 240-858-3366
chuan.wu@nih.gov

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.

NIH Scientific Focus Areas:
Cell Biology, Immunology, Microbiology and Infectious Diseases, Molecular Biology and Biochemistry, Neuroscience
View Dr. Wu's Complete Bibliography at NCBI.

Selected Recent Publications

  1. 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. 2020. [ Journal Article ]
  2. Wu C, Chen Z, Xiao S, Thalhamer T, Madi A, Han T, Kuchroo V.
    Cell Rep. 22(3): 653-65, 2018. [ Journal Article ]
  3. Wu C, Chen Z, Dardalhon V, Xiao S, Thalhamer T, Liao M, Madi A, Franca RF, Han T, Oukka M, and Kuchroo VK.
    Nat Immunol. 18(3): 344-53, 2017. [ Journal Article ]
  4. Chuan Wu, Theresa Thalhamer, Rafael F Franca, Sheng Xiao, Chao Wang, Chie Hotta, Chen Zhu, Mitsuomi Hirashima, Ana C Anderson, Vijay K Kuchroo
    Immunity. 2014. [ Journal Article ]
  5. Chuan Wu, Nir Yosef, Theresa Thalhamer, Chen Zhu, Sheng Xiao, Yasuhiro Kishi, Aviv Regev, Vijay K Kuchroo
    Nature. 2013. [ Journal Article ]

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.

Name Position
Zuojia Chen Ph.D. Postdoctoral Fellow (Visiting)
Girak Kim Ph.D. Postdoctoral Fellow (Visiting)
Jian Li Ph.D. Postdoctoral Fellow (Visiting)
Jialie Luo Ph.D. Scientist (Contr.)