Discovering mechanisms behind liver disease
Dr. Shah's lab focuses on understanding how chronic liver injury drives disease at a cellular and organ level.
Overview
Research in the Integrative Biology of Advanced Liver Disease Laboratory led by Vijay Shah, M.D., focuses on several interrelated areas broadly pertaining to hepatic vascular biology and function. The liver is composed of several cell types, each with its own unique response and contribution to liver disease.
Our research builds on in vitro experiments to identify critical genes and processes that underlie cellular responses to liver injury. This research focuses on:
- The manner in which individual liver-cell types respond and contribute to liver disease.
- Cross talk between liver cells.
- Identifying and developing new hepatic treatment options by exploring underlying biology.
The lab uses multi-omic approaches and big data analytics to explore these issues and generate hypotheses.
One major focus of the lab centers on the mechanisms regulating hepatic fibrogenesis in chronic liver diseases. The lab leverages single-cell transcriptomic and spatial epigenomic technologies to dissect the zonal and cell type-specific programs that drive fibrogenic activation. This is particularly true in hepatic stellate cells and sinusoidal endothelial cells.
Our recent work also explores the role of biomolecular condensates in organizing transcriptional machinery and chromatin regulators within fibrotic niches. This work offers new insight into how stress-responsive transcriptional hubs may govern the persistence of fibrosis.
Our major focus of the clinical research program is alcoholic liver disease. This includes investigating the cellular and molecular mechanisms underlying alcoholic liver disease using single-cell and spatial transcriptomic approaches to identify cell-specific injury responses and molecular pathways altered by chronic alcohol exposure. The program also emphasizes the discovery of biomarkers for diagnosis and prognosis and the development of targeted therapeutics. This is informed by spatially resolved gene regulatory changes and potential alterations in condensate-mediated stress signaling within alcohol-affected hepatic zones.
Affiliations
Dr. Shah's lab is affiliated with these other Mayo Clinic research areas: