Our long-term research objective is to elucidate critical mechanisms by which the apical junctional complex contributes to intestinal epithelial homeostasis and pathogenesis of gastrointestinal disease. The apical junction complex, which includes tight junctions and adherens junctions, is required to regulate intestinal epithelial barrier function and intestinal homeostasis including intestinal stem cells, and becomes dysregulated in important gastrointestinal pathological conditions including ischemic injury and inflammatory bowel disease.
Role of E-cadherin in the intestinal stem cell homeostasis and regeneration. Recent research suggests that facilitation of the mucosal healing by intestinal stem cells (ISC) could be a promising alternative target for difficult-to-treat patients with inflammatory bowel disease (IBD). The Wnt/β-catenin-signaling pathway is one of the critical pathways to regulate the ISC homeostasis and regeneration, and it is critically regulated by adherens junctions (AJs). Both ISCs and AJs are well known as critical players during mucosal healing, but there is a lack of studies that identify the role of AJs in ISC homeostasis and regeneration. Thus, in this project, we can reveal a novel function of AJs in ISC homeostasis and regeneration during the pathogenesis of IBD. Specifically, downregulated E-cadherin in 3D or 2D cultured colonoids will disrupt the ISCs homeostasis with reduced cell-cell adhesion and increased proliferation of the ISCs. The inactivation of E-cadherin during regeneration after injury will also enhance aISCs proliferation with increased Wnt target genes and result in improvement of recovery from injury. Our findings can possibly apply to the manipulation of ISCs in the autologous stem cell transplantation approach to promote mucosal healing in patients with IBD.
Identify the Mechanism of Action of Larazotide Acetate. Larazotide acetate (LA) is a synthetic, eight amino acid peptide that is known to act as a tight junction regulator capable of closing ‘leaky’ interepithelial junctions. Presently, LA is being studied in Phase 3 clinical trials for treatment of celiac disease. However, the mechanism by which LA regulates intestinal barrier is not fully understood. Therefore, we studied the mechanism of action of LA in several different digestive disease models including anoxic injury of Caco-2BBe1 cells and murine IBD models. The cellular pathways regulated by LA were studied using RNAseq, WB, IF, qPCR and etc.
Role of Chloride Channel ClC-2 in Gut Barrier Dysfunction. Treatment of patients with inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis, has been challenging, due to the complexity of this disease and the lack of well-defined therapeutic targets. Dysfunction of the apical junctional complex located within the intercellular spaces of the intestinal epithelium is the most crucial step in initiation of gut inflammation, and we have identified a protein called ClC-2 that plays a pivotal role in regulation of the junctional complex. Additionally, we have preliminary evidence that ClC-2 has a critical role in gut inflammation, which we propose studying using highly innovative self-renewing monolayer culture
Jin, Y. and Blikslager, A.T. (2020). The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases. International Journal of Molecular Sciences, 21 (10), 3550
Jin, Y. and Blikslager, A.T. (2018). Knockout of ClC-2 reveals critical functions of adherens junctions in colonic homeostasis and tumorigenicity. American Journal of Physiology-Gastrointestinal Liver Physiology, 315: G966-G979
Jin, Y. and Blikslager, A.T. (2016). Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury. American Journal of Physiology-Cell Physiology, 311(6):C996-C1004
Jin, Y. and Blikslager, A.T. (2016). Intestinal Ischemia–Reperfusion: Rooting for the SOCS? Digestive Diseases and Sciences, 62(1):pp 4-6
Jin, Y., Prigeon, T. A. and Blikslager, A. T. (2015). Pharmaceutical activation or genetic absence of ClC-2 alters tight junctions during experimental colitis. Inflammatory Bowel Disease, 21(12), 2747-57
Kim, D.G.*, Jin, Y.*, Jin, J.*, Yang, H., Joo, K.M., Lee, S.H., and Nam, D. (2015) Anti-cancer activity of tanibirumab, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR-2/KDR) monoclonal antibody, is associated with inhibition of tumor angiogenesis. mAbs, 7(6), 1195-204
* These authors contributed equally to this work.
Jin, Y. and Blikslager, A.T (2015) ClC-2 regulation of intestinal barrier function: Translation of basic science to therapeutic target. Tissue Barriers, 3 (4), e1105906
Lee, W. S., Pyun, B., Kim, S., Shim, S. R., Yoo, J. Y., Jin, Y., Jin, J., Kwon, Y., Yun, C., Nam, D., Oh, K., Lee, D., Lee, S. H. and Yoo, J. (2015). TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor angiogenesis. mAbs, 7(5), 957-68
Lee, S.J., Seol, H.J., Lee, H.W., Kang, W.Y., Kang, B.G., Jin, J., Jo, M.Y., Jin, Y., Lee, J.I., Joo, K.M. and Nam, D.H. (2013). Gene silencing of c-Met leads to brain metastasis inhibitory effects. Clin Exp Metastasis, 30(7), 845-54
Kim, D.G., Jin, Y., Jin, J.Y., Kim, S.C., Kim, S.C., Han, C.H. and Lee, Y.J. (2011). Effects of the Actindia chinensis on Loperamide-induced Constipation in Rat. The Plant Resources Society of Korea, 24(1), 1-112
Lee, J.C.*, Jin, Y.*, Jin, J., Kang, B.G., Nam, D.H., Joo, K.M. and Cha, C.I. (2011). Functional neural stem cell isolation from brains of adult mutant SOD1 (SOD1(G93A)) transgenic amyotrophic lateral sclerosis (ALS) mice. Neurol Res, 33(1), 33-7
* These authors contributed equally to this work.
Jin, J., Joo, K.M., Lee, S.J., Jo, M.Y., Kim, Y., Jin, Y., Kim, J.K., Ahn, J.M., Yoon, M.J., Lim, J., and Nam, D.H. (2011). Synergistic therapeutic effects of cytokine-induced killer cells and temozolomide against glioblastoma. Oncol Rep, 25(1), 33-9
Lee, S.J., Kim, Y., Jo M.Y., Kim, H.S., Jin, Y., Kim, S.U., Jin, J., Joo, K.M., and Nam, D.H. (2011). Combined treatment of tumor-tropic human neural stem cells containing the CD suicide gene effectively targets brain tumors provoking a mild immune response. Oncol Rep, 25(1), 63-8.
Jin, J., Joo, K.M., Nam, Y., Kim, D.H., Lee, S.J., Jo, M.Y., Jin, Y., Kim, H.S., Seo, S.W., Kim, S.J., Na m, D.H. and Kim, W.S. (2010). Schedule-dependent synergistic effect of rituximab on methotrexate chemotherapy against lymphoma of the central nervous system. Experimental and Therapeutic Medicine, 1(6), 943-946
Jin, Y., Kim, D.G., Jin, J.Y., Lee Y.J. and Park, M.K. (2007). Effects of Lentinus edodes Extract on the Loperamide-induced Constipation in Rats. Korean Society of Food Science and Technology (KoSFoST), 39(1), 88-93
Jin, J.Y., Yang, H.K., Kim, J.M., Ko, M.S., Hong, H.J., Jin, Y., Kim, D.G., Kim, S.C., Lee, I., Hyon, M.K., Kang, S.C., Kim, J.H. and Lee, Y.J. (2006). Four-week Repeated Oral Toxicity Study of the Extract of Aralia elata in Rats. Journal of Toxicology and Public Health, 22(4), 445-452
2021 - present:
ANSC 445: Comparative Digestive Pathophysiology
Certificate of Recognition - 2018
Digestive Disease Week
For Your Scientific Accomplishment As An Early Career Investigator
Notable Poster - 2018
2018 Postdoctoral Research Symposium
NC State University
2017-2018 Professional Development Award for Postdocs - 2017
Office of Postdoctoral Affairs, Graduate
NC State University
Travel Award - 2017
2017 FASEB Gastrointestinal Tract XVII
Current Biology of the GI Tract, Mucosa, Microbiota, and Beyond Conferences
Postdoctoral Scholar of the Year Award - 2016
The Department of Clinical Sciences of NC State University
College of Veterinary Medicine