Younggeon Jin

Current Research:

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. 

Role of Intestinal Mesenchymal Stromal Cells in the Porcine Intestinal Development. The intestinal tract has a considerably immature organ and undergoes substantial changes after birth. Recently, the role of intestinal mesenchymal stromal cells (iMSCs) in regulating intestinal stem cells (ISCs) and their differentiation during development was highlighted. Thus, our aim of this proposed study is to identify the role of iMSCs in their interaction with epithelium during postnatal intestinal development and find novel mechanisms of nutritional factors to improve intestinal health in pigs. This will lead us to investigate how nutrient sources enhance the intestinal development related to MSCs/IECs interactions and enhance our understanding of the mechanistic connections between nutrients and gut health to improve pig growth. 

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.

1. 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

2. 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

3. 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

4. Jin, Y. and Blikslager, A.T. (2016). Intestinal Ischemia–Reperfusion: Rooting for the SOCS? Digestive Diseases and Sciences, 62(1):pp 4-6

5. 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

6. 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.

7. 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

8. 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

9. 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

10. 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

11. 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.

12. 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

13. 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.

14. 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

15. 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

16. 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

   ANSC 445: Comparative Digestive Pathophysiology

   ANSC 645: Advanced Studies in Comparative Digestive Pathophysiology

• LAUNCH program, Maryland Stem Cell Research Fund, 2021-2023

• Maryland Agricultural Experiment Station (MAES) Competitive Grant Program, 2020-2021

• Innovate Biopharmaceuticals, Inc. 2019-2021

• Pilot/Feasibility Grant, Center for Gastrointestinal Biology and Disease, 2017-2018

• 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