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The research in Dr. Han
laboratory is currently focused on the pathogenesis of chronic gastrointestinal
injuries, and development of potential treatments for enteric infection and
inflammation in the pediatric patients. His lab projects include:
Stem cell therapy has recently achieved many successful cases in the personalized treatment of chronic and persistent mucosal inflammation; however, trans-differentiation of these stem cells into different cell types causes numerous problems. It was reported that intestinal epithelial stem cell-derived enteroids have a better potential in healing gastro-intestinal ulceration, but lack of fundamental mechanisms significantly blocks the development of intestinal stem cell treatment. Cytokine/JAK/STAT signaling is suggested to mediate intestinal stem cell homeostasis. In this project, we mainly focus on investigation of the role of JAK/STAT signaling in the adult stem cell responses to intestinal injury. Using a series of proof-of-concept studies with JAK-STAT mutant mice, mouse or human adult stem cells, we will, first, characterize the role of JAK-STAT signaling in adult stem cell differentiation; second, we will define the sufficiency of activation of JAK-STAT signaling for intestinal barrier differentiation. We believe that our investigations will permit a collaborative team of basic scientists and clinical investigators to start a novel potential therapeutic avenue for restoring intestinal hemostasis. Our work will be beneficial to obtain molecular insights to fight diseases driven by intestinal infection or chronic inflammation with impact on cancer manifestation. This project is a collaborative study with Intestinal Rehabilitation Research Program, Development Biology and Pediatric Surgery at Cincinnati Children's, and Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna, Austria.
organ barrier function is highly involved in the pathogenesis of chronic
degenerative diseases, for instance, inflammatory bowel diseases (IBD).
However, the mechanisms and regulation are poorly defined. We reported that a
negative feed-back loop STAT5→NF-κB → MLCK) directly regulates intestinal barrier function and response to
injury relevant to human IBD (see Figure, EMBO Molecular Medicine, 2012). In the subsequent investigations,
we will test the requirement of epithelial STAT5 signaling during the
treatments and repair of mucosal inflammation with stem cell growth factors, cytokines or
natural plant compounds known to be beneficial or detrimental for GI tract
repair. These studies will not only lead to increased scientific knowledge of
mucosal innate immunity, but these studies will also provide a novel
therapeutic target for treatment of epithelial barrier dysfunction in IBD or
colon cancer. This project is a collaborative study with the IBD center, division
of Allergy and Immunology, and division of Bioinformatics, Intestinal Rehabilitation Research Program, Cincinnati Children's Hospital, University of Chicago in Chicago and the
Ludwig Boltzmann Institute of Cancer Research in Vienna, Austria.
Gilbert S, Nivarthi H, Mayhew CN, Lo YH, Noah TK, Vallance J, Rülicke T, Müller M, Jegga AG, Tang W, Zhang D, Helmrath M, Shroyer N, Moriggl R, Han X. Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration.Stem Cell Reports. 2015 Jan 7. pii: S2213-6711(14)00381-6. doi: 10.1016/j.stemcr.2014.12.004. [Epub ahead of print]
Yang F, Zhou L, Wang Q, You X, Li Y, Zhao Y, Han X, Chang Z, He X, Cheng C, Wu C, Wang WJ, Hu FY, Zhao T, Li Y, Zhao M, Zheng GY, Dong J, Fan C, Yang J, Meng X, Zhang Y, Zhu X, Xiong J, Tian XL, Cao H2. NEXN inhibits GATA4 and leads to atrial septal defects in mice and humans. Cardiovasc Res. 2014 Jul 15;103(2):228-37. doi: 10.1093/cvr/cvu134. Epub 2014 May 27
Melendez J, Liu M, Sampson L, Akunuru S, Han X, Vallance J, Witte D, Shroyer N, Zheng Y. Cdc42 coordinates proliferation, polarity, migration, and differentiation of small intestinal epithelial cells in mice. Gastroenterology. 2013 Oct;145(4):808-19. doi: 10.1053/j.gastro.2013.06.021. Epub 2013 Jun 20.
Xiaonan Han, PhD
Division of Gastroenterology, Hepatology and Nutrition3333 Burnet Ave.Cincinnati, OH 45229
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