Juhoon So, Ph.D.

  • Assistant Professor

During liver regeneration, biliary epithelial cell (BEC)-driven liver regeneration occurs when hepatocyte-driven liver regeneration is not sufficient or is compromised, which is the case in chronic liver diseases. A correlation between liver progenitor cells (LPCs) and disease severity in patients with chronic liver diseases suggest that BEC­driven liver regeneration can be initiated, but activated LPCs fail to efficiently differentiate into hepatocytes in the patients. Promoting LPC differentiation into hepatocytes could recover injured liver by generating more functional hepatocytes and reducing the number of LPCs that contribute to fibrosis via secreting pro-inflammatory factors. Despite this significance, the molecular basis of LPC differentiation into functional hepatocytes remains unclear.

We have established zebrafish chronic liver injury models, in which hepatocyte-specific overexpression of oncogenes leads to LPC-mediated liver repair. Hepatocyte damage, LPC activation, fibrosis, and LPC differentiation into hepatocytes sequentially occurr in oncogene-expressing transgenic zebrafish, similarly observed in mammalian chronic liver injury models. These zebrafish models have a great potential to reveal the molecular mechanisms underlying LPC-driven liver regeneration and to identify compounds that can promote LPC differentiation into hepatocytes. Using the zebrafish models, we aim to delineate the detailed steps of LPC-driven liver regeneration. Such elucidation will enable investigation of the roles of genes and pathways in LPC-driven liver regeneration and will provide a framework to test the effects of various molecules on LPC differentiation.

Additionally, we observed liver inflammation and fibrosis in the zebrafish chronic liver injury models. Liver fibrosis is a process of wound-healing responses upon liver damages and arises a major human health problem. Although the pathogenesis of liver fibrosis is well studied, effective anti-fibrotic therapies are still lacking. In order to elucidate the molecular mechanisms underlying the progression and resolution of liver fibrosis and to develop novel and effective anti-fibrotic therapies, we will perform a chemical screen using the zebrafish liver fibrosis model. This screening will allow for understanding the molecular mechanisms underlying liver fibrosis and identifying novel targets for effective anti-fibrotic therapies.

Education & Training

  • Ph.D. from Chungnam National University, Daejeon, South Korea, 2010
  • M.S. from Chungnam National University, Daejeon, South Korea, 2005
  • B.S. from Kyungpook National University, Daegu, South Korea, 2003

Representative Publications

• Jung K, Kim M, So J, Lee SH, Ko S, Shin D (2020), Farnesoid X receptor activation impairs liver progenitor cell-mediated liver regeneration via the PTEN-PI3K-AKT-mTOR axis in zebrafish. Hepatology, Dec 13. doi: 10.1002/hep.31679

• So J, Ningappa M, Glessner J, Min J, Ashokkumar C, Ranganathan S, Higgs BW, Li D, Sun Q, Schmitt L, Biery AC, Dobrowolski S, Trautz C, Fuhrman L, Schwartz MC, Klena NT, Fusco J, Prasadan K, Morayooluwa A, Mohamed N, Yan Q, Chen W, Horne W, Dhawa A, Sharif K, Kelly D, Squires RH, Gittes GK, Hakonarson H, Morell V, Lo CW, Subramaniam S, Shin D, Sindhi R (2020), Biliary-atresia-associated mannosidase-1-alpha-2 gene regulates biliary and ciliary morphogenesis and laterality. Frontiers in Physiology, 11:538701.

• Min J, Ningappa M, So J, Shin D, Sindhi R, Subramaniam S (2020), Systems analysis of biliary atresia through integration of high-throughput biological data. Frontiers in Physiology, 11:966.

• So J, Kim M, Lee SH, Ko S, Lee DA, Park H, Azuma M, Parsons MJ, Prober D, Shin D (2020), Attenuating the EGFR-ERK-SOX9 axis promotes liver progenitor cell-mediated liver regeneration in zebrafish. Hepatology, doi: 10.1002/hep.31437

• So J, Kim A, Lee SH, Shin D (2020), Liver progenitor cell-driven liver regeneration. Exp Mol Med, 52(8):1230-1238

• So J, Khaliq M, Evason K, Ninov N, Martin BL, Stainier DY, Shin D (2018), Wnt/β-catenin signaling controls intrahepatic biliary network formation in zebrafish by regulating Notch activity. Hepatology, 67:2352-2366.

• Xiao Zhao, Kristin Lorent, Benjamin J. Wilkins, Dylan M. Marchione, Kevin Gillespie, Orith Waisbourd-Zinman, Juhoon So, Kyung Ah Koo, Donghun Shin, John R. Porter, Rebecca G. Wells, Ian Blair, and Michael Pack. Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish. Hepatology. 64(3):894-907.

• Sungjin Ko, Tae-Young Choi, Jacquelyn O. Russell, Juhoon So, Satdarshan P.S. Monga, and Donghun Shin. (2016) Bromodomain and extraterminal (BET) proteins regulate biliary-driven liver regeneration. Journal of Hepatology. 64(2):316-325.

• Mylarappa Ningappa*, Juhoon So*, Joseph Glessner, Chethan Ashokkumar, Sarangarajan Ranganathan, Jun Min, Brandon W. Higgs, Qing Sun, Kimberly Haberman, Lori Schmitt, Silvia Vilarinho, Pramod K. Mistry, Gerald Vockley, Anil Dhawan, George K. Gittes, Hakon Hakonarson, Shankar Subramaniam, Donghun Shin, Rakesh Sindhi. (2015) The Role of ARF6 in Biliary Atresia. PLOS ONE. 10(9):e0138381. (*These authors contributed equally to the work)

• Tae-Young Choi, Mehwish Khaliq, Sungjin Ko, Juhoon So, Donghun Shin. (2015) Hepatocyte-specific Ablation in Zebrafish to Study Biliary-driven Liver Regeneration. Journal of Visualized Experiments. 20(99)

• Mehwish Khaliq, Tae-Young Choi, Juhoon So, Donghun Shin. (2015) Id2a is required for hepatic outgrowth during liver development in zebrafish. Mechanisms of Development. 138 Pt 3:399-414

• Ju-Hoon So, Jun-Dae Kim, Kyeong-Won Yoo, Hyun-Taek Kim, Seung-Hyun Jung, Jung-Hwa Choi, Mi-Sun Lee, Suk-Won Jin, Cheol-Hee Kim. (2014) FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development. PLOS ONE. 9(10):e109517.

• Evan R. Delgado, Jing Yang, Juhoon So, Stephanie Leimgruber, Michael Kahn, Tohru Ishitani, Donghun Shin, Gabriela Mustata Wilson, Satdarshan P. Monga. (2014) Identification and characterization of a novel small-molecule inhibitor of β-catenin signaling. The American Journal of Pathology. 184(7): 2111-2122.

• Juhoon So, Benjamin L. Martin, David Kimelman, and Donghun Shin. (2013) Wnt/β-catenin signaling cell-autonomously converts non-hepatic endodermal cells to a liver fate. Biology Open. 2 (1): 30-36.

• Jae Hong Lee*, Ju-Hoon So*, Jong Hyun Jeon, Eun Bok Choi, Yu-Ri Lee, Young-Tae Chang, Cheol-Hee Kim, Myung Ae Bae and Jin Hee Ahn. (2011) Synthesis of a new fluorescent small molecule probe and its use for in vivo lipid imaging. Chemical Communications. 47 (26): 7500-7502. (*These authors contributed equally to the work) 

• Ju-Hoon So, Sung-Kook Hong, Hyun-Taek Kim, Seung-Hyun Jung, Mi-Sun Lee, Jung-Hwa Choi, Young-Ki Bae, Tetsuhiro Kudoh, Ji-Hun Kim and Cheol-Hee Kim. (2010) Gicerin/Cd146 is involved in zebrafish cardiovascular development and tumor angiogenesis. Genes to Cells. 15 (11): 1099-1110.

Research Interest Summary

Liver development, regeneration and cancer

Research Interests

1. Roles of Sall4 in liver development, regeneration, and cancer

2. Roles of Fgf signaling in liver progenitor cell-mediated liver regeneration