Innovating Works

ForgettingNAFLD

Financiado
Unravelling the pathogenic cell-cell circuits underlying the tissue memory of no...
Unravelling the pathogenic cell-cell circuits underlying the tissue memory of non-alcoholic fatty liver disease With the obesity epidemic, global prevalence of non-alcoholic fatty liver disease (NAFLD) is currently at 25% and rising. NAFLD results from accumulation of excessive fat in the liver and covers a spectrum of disease states from s... With the obesity epidemic, global prevalence of non-alcoholic fatty liver disease (NAFLD) is currently at 25% and rising. NAFLD results from accumulation of excessive fat in the liver and covers a spectrum of disease states from simple steatosis (fatty liver) to severe non-alcoholic steatohepatitis (NASH). NAFLD patients are also at increased risk of developing secondary pathologies, including infections and paracetamol-induced liver damage, although the mechanisms behind this remain unclear. As no pharmacological treatment of NAFLD exists to date, patients are typically instructed to lose weight as this can alleviate symptoms. However, with the recent proposal of tissue memory of inflammation, including NAFLD, it is unclear if weight loss alone is sufficient to restore liver homeostasis or if recovered NAFLD patients remain more susceptible to secondary inflammatory events. Recently, the host labs have identified key cell-cell circuits that control the functional specialization of liver resident macrophages in the steady-state and fatty liver. These findings led me to hypothesize that NAFLD could lead to tissue memory by disrupting the interactions between resident liver cells and establish aberrant cell-cell circuits that maintain a pathological state even after weight loss. Furthermore, I postulate that this NAFLD memory could facilitate the relapse into NAFLD but also modulate susceptibility to secondary insults. Indeed, my preliminary data indicates altered susceptibility to paracetamol overdose. Here, I propose to use single-cell RNA sequencing and epigenetics to investigate how cell-circuits in the liver are perturbed after NAFLD regression and identify the signals underlying these alterations. This project will further our understanding on how liver circuits are distorted in disease and could provide therapeutic avenues to ‘reset’ pathogenic liver circuits in patients currently suffering from NAFLD or those in the process of weight loss and recovery. ver más
30/09/2024
VLAAMS INSTITUUT...
176K€
Perfil tecnológico estimado
Duración del proyecto: 26 meses Fecha Inicio: 2022-07-01
Fecha Fin: 2024-09-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-09-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021
Cerrada hace 3 años
Presupuesto El presupuesto total del proyecto asciende a 176K€
Líder del proyecto
VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5