Alexander Rosajel-Gutierrez
Research Mentor: Xin Tong
Mentor Department: Molecular & Integrative Physiology, Medicine
Author(s): Not Available
Session: Session 7 (4:00 PM – 4:50 PM)
Presentation Type: Poster 75
Abstract
Liver fibrosis is a progressive and potentially irreversible condition characterized by excessive extracellular matrix deposition driven by the activation of hepatic stellate cells (HSCs). Despite its significant clinical burden, effective targeted therapies remain limited due to an incomplete understanding of the molecular mechanisms underlying disease progression. Recent studies have identified hepatic carbohydrate response element-binding protein alpha (ChREBPa) as a key suppressor of liver fibrosis and a regulator associated with metabolic-associated steatotic liver disease (MASLD). ChREBPa inhibits the TGF-ß–E2F1 signaling axis, thereby reducing the expression of profibrogenic factors such as THBS1 and CTGF. Loss of ChREBPa promotes HSC activation and accelerates fibrotic progression, whereas restoration of ChREBPa attenuates fibrosis independently of lipid metabolism, highlighting a novel regulatory role within the hepatic microenvironment. Recent advances in CRISPR-Cas9 genome editing provide powerful tools for precise genetic manipulation in vivo. Compact Cas9 systems delivered through adeno-associated virus (AAV) vectors enable efficient targeting of hepatocytes while improving delivery efficiency and specificity. Together, these findings suggest that CRISPR-based therapeutic strategies targeting the ChREBPa–E2F1 signaling pathway may offer a promising approach for treating liver fibrosis. By directly modulating key regulators of fibrogenesis, this framework provides a potential avenue for the development of precise gene-based therapies for chronic liver disease.
