National Institute of Diabetes and Digestive and Kidney Diseases 5R01DK136848-04

Innate Immunity in NASH

This award funds research on the role of the innate immune system, particularly macrophage cGAS-STING pathway, in the progression and pathogenesis of NASH, aiming to identify new therapeutic targets.

Description

Nonalcoholic steatohepatitis (NASH), a cell death and inflammation-associated nonalcoholic fatty liver disease (NAFLD), is the leading cause of hepatocellular carcinoma (HCC) and end-stage liver failure worldwide. There is no effective therapeutic drug for NASH to date, highlighting an urgent need for the identification of novel targets for this devastating disease. Evidence accumulated over the past decade strongly suggests that the innate immune system, specifically the liver-resident macrophages (Kupffer cells) and recruited monocyte-derived macrophages, play a key role in NASH progression and pathogenesis. The current study aims to elucidate the mechanisms by which macrophage cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway regulates liver fibrosis and NASH pathogenesis. The study will investigate how cGAS deficiency affects macrophage function and liver disease progression, potentially revealing new therapeutic targets.

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