• J1-9176 - ClolesteROR in metabilic liver disease
The Client : Javna agencija za raziskovalno dejavnost RS ( J1-9176 )
Project type: Research projects ARRS
Project duration: 2018 - 2021
  • Description

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in the world. It affects 25% of the global adult population and as many as 1/3 of people in the developed world. The disease is manifested by a spectrum of liver pathologies ranging from simple steatosis to liver cell injury with fibrosis and can end in cirrhosis or liver cancer (Hepatocellular Carcinoma). This project aims to address some of the current unmet needs in identifying molecular players of NAFLD. We will focus on the new promising players: the CholesteROR pathway that links Retinoic Acid Orphan Receptor Gamma signalling (ROR-gamma, RORC, NR1F-3) to cholesterol. At this point the literature is sparse and the endogenous function of the hepatic RORC signalling is in its early phase of understanding. To solve such complex questions in multifactorial pathologies we must apply innovative systems solutions that in addition to experimentation include also modelling and validation in clinical samples. Computational part of the project will include statistical and dynamical modelling that will provide novel insights into the role of CholesteROR pathway in the development of NAFLD. We will develop general mechanistic models of disease progression that will be applied to specific individuals (development of personalised models). Personalised models will be able to predict different NAFLD modulators and will finally allow us to personalise the diagnostic and therapeutic interventions to each inidividual patient.