Summary
This project aims to understand the molecular mechanisms by which the Constitutive Androstane receptor (CAR) regulates liver growth, metabolism, and regeneration, with a specific focus on sex differences in these processes.
Understanding Mechanisms that Regulate Liver Growth and Function
US · IL
NIH
grant
open
#nih-5R01DK113080-07
What they want
The study will investigate how CAR regulates zonation, polyploidy, injury-associated regeneration, influences estrogen receptor α (ERα)-mediated signaling, and contributes to sex differences in liver metabolism and functions. It will utilize high throughput analysis of transcriptomes and cistromes, a novel epitope-tagged FLAG-CAR mouse, and different chemical-based liver injury models. Specific aim 1 will determine if CAR is necessary for metabolic maturation and maintaining hepatocyte heterogeneity. Specific aim 2 will determine the role of the CAR-ERα axis in regulating sex differences in polyploidy and regeneration in the liver. The long-term objective is to gain a comprehensive understanding of molecular mechanisms integrating metabolic functions and liver regeneration/growth to inform prevention and treatment of liver diseases.
Deliverables
- Comprehensive understanding of molecular mechanisms integrating metabolic functions and liver regeneration and growth
- New insights into CAR's role in controlling hepatocyte metabolic fitness
- Knowledge that can be maneuvered to prevent and/or treat liver diseases
Technical requirements
- High throughput analysis of transcriptomes and cistromes
- Use of a novel epitope-tagged FLAG-CAR mouse
- Use of different chemical-based liver injury models
