U.S. Department of Health and Human Services
Jake Liang
 

 Contact Info

 
Tel: 301-496-1721
Email: jakel@mail.nih.gov
 

 Select Experience

 
  • M.D.Harvard Medical School1984
  • B.A.Harvard College1980
 

 Related Links

 
Specialties
  • Clinical Research
  • Genetics/Genomics
  • Immunology
  • Stem Cells/Induced Pluripotent Stem Cells
  • Virology

​Research Images

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TitleDescriptionImage
Systems Biology of Host Factors in HCV Life Cycle

Using the complete HCV replication cycle (from entry to secretion) as a framework, all verified HCV host dependencies from this study were placed based on their predominant subcellular localization and relevance to particular stages of the viral life cycle. In addition, multiple datasets from other HCV siRNA screens and existing publications were mined, explored and integrated into a comprehensive up-to-date dataset of HCV interacting host factors. Computational mapping was performed to reconstitute the map that was further refined manually. HPFs (host proviral factors) are shown in red square, HAFs (host antiviral factors) are shown in green circle. Previously published HCV host dependencies that were also identified in this study are shown in yellow, and other known HCV host factors that were not identified in this study are shown in orange (HPF in circle and HAF in square).

Systems Biology of Host Factors in HCV Life CycleEnlarge
HCV Infection, Interferon Response and Lipid Droplet Biogenesis

A proposed model of innate antiviral response and HCV-induced lipogenesis and LD formation in HCV assembly. HCV can activate two distinct pathways. One is the induction of interferon pathway by interaction of HCV PAMP with RIG-I helicase like receptor (pattern recognition receptor) and the other is activation of lipogenic pathway via stress granule, DDX3X and Ikkα, that facilitates HCV assembly.

HCV Infection, Interferon Response and Lipid Droplet BiogenesisEnlarge
HCV Infection, I-SMAD and Lipid Metabolism

A proposed model for I-SMAD-regulated signaling that enhances HSPG expression, cholesterol uptake and HCV entry. HCV entry is mediated by viral binding to HSPGs, LDLR and SR-BI (and other entry factors, not shown) on the host cell surface, thereby triggering a cassette of signaling to facilitate the internalization of HCV virions. HCV infection also induces the expression of SMAD6 and SMAD7, two I-SMADs of the TGF-β signaling pathway via NF-κB regulation. The I-SMADs translocate to the nucleus and transcriptionally activate the expression HSPG core protein and other cholesterol uptake receptors. Increased expression level of heparin sulfate on the cell surface in turn enhances HCV binding. Additionally, the I-SMADs and HSPGs can be induced by BMP6 and BMP7, the ligands in the BMP/TGF-β pathway. 

HCV Infection, I-SMAD and Lipid MetabolismEnlarge
iPSC-derived human hepatocytesHuman hepatocytes, generated from induced pluripotent stem cells derived from a patient, produce and exhibit hepatocyte-specific proteins (albumin) and functions (lipid and glycogen storage, organic anion transport). This regenerative medicine technology can be a valuable strategy for cell-based therapy of liver diseases.iPSC-derived human hepatocytesEnlarge
Induction of steatosis by HCVHCV infection of human hepatocyte-derived cells induces a lipogenic program that results in massive accumulation of lipid droplets (green and yellow structures). This is known as steatosis and is essential for HCV propagation.Induction of steatosis by HCVEnlarge