Donghun Shin, Ph.D.

  • Associate Professor

During regeneration, hepatocytes can be derived from either preexisting hepatocytes or biliary epithelial cells (BECs). When hepatocyte-driven liver regeneration is compromised, which is the case in chronic liver diseases, BEC-driven liver regeneration takes place. Understanding the molecular mechanisms of this BEC-driven liver regeneration should provide significant insights into how to promote innate liver regeneration in patients with severe liver diseases as therapeutics. We have established several innovative zebrafish liver regeneration models in which BECs extensively give rise to hepatocytes. Using these models, we have taken several approaches to better understand the mechanisms of BEC-driven liver regeneration, including chemical screening and RNAseq analyses. Currently, we investigate how (1) epigenetic factors, (2) metabolism, (3) EGFR signaling, and (4) FXR signaling regulate BEC-driven liver regeneration.

Upon severe biliary damage, hepatocytes transdifferentiate into BECs, similar to BEC convertion to hepatocytes in the settings of severe hepatocyte damage. We recenlty developed two zebrafish models for hepatocyte-to-BEC transdifferentiation. Using these models, we investigate the molecular mechanisms underlying this plasticity.

Education & Training

  • Postdoc in the Stainier lab, UCSF, San Francisco, CA, 2010
  • Ph.D. from California Institute of Technology, Pasadena, CA, 2005
  • M.S. from Seoul National University, Seoul, Korea, 1997
  • B.A. from Seoul National University, Seoul, Korea, 1995

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 [Abstract]

• 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. [Abstract]

• 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 [Abstract]

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

• Russell JO, Ko S, Monga SP, Shin D (2019), Notch inhibition promotes differentiation of liver progenitor cells into hepatocytes via sox9b repression in zebrafish. Stem Cells International, Mar 12;2019:8451282 [Abstract]

• Ko S, Russell JO, Tian J, Gao C, Kobayashi M, Feng R, Yuan X, Shao C, Ding H, Poddar M, Singh S, Locker J, Weng HL, Monga SP, Shin D (2019), Hdac1 regulates differentiation of bipotent liver progenitor cells during regeneration via Sox9b and Cdk8. Gastroenterology, 156(1):187-202 [Abstract]

• Khaliq M, Ko S, Liu Y, Wang H, Sun Y, Solnica-Krezel L, Shin D (2018), Stat3 regulates liver progenitor cell-driven liver regeneration in zebrafish. Gene Expression, 18:157-170. [Abstract]

• 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. [Abstract]

• Choi TY, Khaliq M, Tsurusaki S, Ninov N, Stainier DY, Tanaka M, Shin D (2017), Bmp signaling governs biliary-driven liver regeneration in zebrafish via Tbx2b and Id2a. Hepatology, 66:1616-1630. [Abstract]
• Ko S, Choi TY, Russell JO, So J, Monga SP, Shin D (2016) Bromodomain and extraterminal domain (BET) proteins regulate biliary-driven liver regeneration, J Hepatology, 64:316-25. [Abstract]
• Choi TY, Ninov N, Stainier DY, Shin D (2014), Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish. Gastroenterology, 146(3):776-788. [Abstract]
• So J, Martin BL, Kimelman D, Shin D (2013), Wnt/β-catenin signaling cell-autonomously converts non-hepatic endodermal cells to a liver fate. Biol Open, 2:30-6. [Abstract]
• Shin D, Lee Y, Poss KD, Stainier DY (2011), Restriction of hepatic competence by Fgf signaling. Development, 138:1339-48. [Abstract]

Research Interest Summary

Liver development, regeneration and cancer

Research Interests

1. The molecular mechanisms underlying liver progenitor cell-mediated liver regeneration
2. The molecular mechanims of hepatocyte-to-cholangiocyte reprogramming
3. The molecular mechanisms of liver development
4. Roles of Sall4 in liver development, regeneration, and cancer

Research Grants

• NIH R01 DK101426: Elucidating the role of the FXR-PTEN-PI3K-AKT axis in liver progenitor cell-driven liver regeneration
• NIH R01 DK109365: Mapping disease pathways for biliary atresia
• NIH R01 DK116993: Delineating molecular mechanisms underlying liver progenitor cell-driven liver regeneration