Sergei Kutseikin

A New Approach to Treating Fatty Liver Disease
Summary
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a condition where fat builds up in the liver, and in its severe form, metabolic dysfunction-associated steatohepatitis (MASH), this buildup leads to inflammation, liver cell damage, and liver scarring. These disorders are more common in people with metabolic conditions like type 2 diabetes or obesity. There are limited approved treatments, and development of new therapies is challenging given the disease is driven by a complex mix of metabolic issues. A common feature in obesity-linked organ defects is an imbalance in the cell’s natural stress response system. We have developed drugs that help fix this by boosting the protective signals of the stress response system. Studies in obese-diabetic mice show treatment with these drugs improved metabolic health. My project will investigate these drugs in MAFLD/MASH mouse models and uncover their molecular mechanism of action. Our goal is to develop effective new treatments for MAFLD/MASH, improving liver function and overall metabolic health.
I am deeply honored to receive the PhRMA Foundation Predoctoral Fellowship. This award will aid in advancing my research on pharmacologic IRE1/XBP1s activation, a promising approach to correct liver dysfunction in MASLD/MASH, an unmet medical need.