OBJECTIVE
Using the liver as our model organ, we aim to understand how tissues function and adapt in different pathological settings to identify early disease biomarkers and engineer ways to revert them to homeostasis.
Liver diseases generally arise in the context of repeated perturbations but current models do not fully recapitulate this process. Thus to better understand how liver disease progresses, we will develop models that enable us to trace the molecular evolution of how the liver adapts to repeated injuries, and distinguish beneficial from maladaptive responses. Our lab focuses on the liver because of its unique regenerative ability that promotes adaptation to constant exposure from both external and internal perturbations.
Evolution of Liver Adaptation to Repeated Injury
Sex Differences in Liver Adaptation
Liver disease progression is often influenced by biological sex differences but the molecular mechanisms governing these events remain unresolved. We will use genome-wide screening tools, molecular, and biochemical analyses to unpick how hormones and sex-specific epigenetic changes influence liver adaptation that will ultimately promote progression to alcoholic liver disease, metabolic-associated fatty liver disease, and liver cancer.
Systemic Effects of Liver Adaptation
In chronic diseases, there is a new state of ‘homeostasis’ in which the human body adopts compensatory mechanisms for survival but these often give rise to systemic changes that can lead to more health problems. To understand how a localized event in the liver promotes whole-body disease susceptibility to vascular problems, we will dissect the crosstalk between these tissues using genetic, pharmacologic, and biochemical approaches in ex vivo and in vivo injury models.