University of Pittsburgh Department of Cell Biology
  • Research

    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, and (3) FGFR signaling regulate BEC-driven liver regeneration.

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

  • Publications

    1. Kim M, Rizvi F, Shin D, Gouon-Evans V. Update on Hepatobiliary Plasticity.. Semin Liver Dis. 2023 Feb;43(1):13-23. doi: 10.1055/s-0042-1760306. PubMed PMID: 36764306;
    2. Lee SH, So J, Shin D. Hepatocyte-to-cholangiocyte conversion occurs through transdifferentiation independently of proliferation in zebrafish.. Hepatology. 2023 Apr 1;77(4):1198-1210. doi: 10.1097/HEP.0000000000000016. PubMed PMID: 36626626;
    3. Jung K, Kim M, So J, Lee SH, Ko S, Shin D. Farnesoid X Receptor Activation Impairs Liver Progenitor Cell-Mediated Liver Regeneration via the PTEN-PI3K-AKT-mTOR Axis in Zebrafish.. Hepatology. 2021 Jul;74(1):397-410. doi: 10.1002/hep.31679. PubMed PMID: 33314176;


Quick Links