Shijun Deng, PhD

Pilot Research Award
$50,000 over one year

President and Fellows of Harvard College, Harvard T. H. Chan School of Public Health

Defining Lipoprotein Endpoints of AAV-NFE2L1 Gene Therapy for MASH-Associated Atherogenic Dyslipidemia

The liver is one of the body’s most important organs. One of its key jobs is to manage fats and cholesterol and send them into the bloodstream in the right balance. When the liver is healthy, this process works well. But in people with metabolic dysfunction-associated steatohepatitis, or MASH, the liver becomes inflamed and damaged and can no longer handle fats properly. As a result, the blood contains more harmful fat particles that can clog arteries and increase the risk of heart attack and stroke. In fact, many people with MASH are more likely to die from heart disease than from liver failure itself.

My research focuses on understanding why this happens. I study two proteins inside liver cells, NFE2L1 and INSIG1, that act like a control switch for cholesterol balance. When this switch works normally, the liver stays healthier and packages fats in a safer form. When the switch breaks down, the liver becomes injured and begins releasing more harmful particles into the blood. This discovery was recently accepted for publication in the Journal of Clinical Investigation. In this project, I will study how this switch works and what happens when it fails, using specially bred laboratory mice to measure how the liver handles cholesterol when this pathway is disrupted. I will also test whether restoring the pathway can bring these processes back toward normal.

This work will help explain why MASH increases the risk of heart disease, and in the long term, may guide the development of new treatments that protect both the liver and the heart in people living with MASH.