In two parallel breakthrough studies, Cedars-Sinai researchers have mapped the molecular blueprints of alcohol-associated liver disease, identifying two critical targets—FOXM1 and SRC—that could finally unlock effective treatments for a condition that kills nearly half of all Americans who die from liver disease.
Alcohol-associated liver disease is a silent killer. Chronic drinking triggers inflammation and scarring of the liver that can spiral into total organ failure, forcing some patients to the transplant list. For decades, the only proven intervention has been abstinence, which remains difficult for those whose addiction drives the damage. The medical community has lacked concrete therapeutic options, leaving patients with little hope beyond behavior change alone.
Dr. Shelly Lu, director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai, and her team published their findings on FOXM1 in Hepatology. Working with alcohol-exposed human liver tissue, liver cells, and laboratory mice, the researchers discovered that FOXM1—a protein already known to drive other liver diseases including cancer—acts as a master conductor. It controls an entire network of genes and proteins that orchestrate both the scarring and inflammation that destroys livers. When the team suppressed FOXM1, something remarkable happened: the liver scarring reversed. "We found that FOXM1 is a key regulator of alcohol-associated liver disease progression and represents a promising target for therapeutic intervention," Lu said.
Meanwhile, a separate Cedars-Sinai team, led by Dr. Maria Lauda Tomasi and published in Science Advances, zeroed in on how alcohol actually triggers the damage at the molecular level. They traced the mechanism to an enzyme called SRC and a protein called UBC9. When alcohol exposure activates SRC, it modifies UBC9 through a process called phosphorylation—essentially putting the immune system on high alert in ways that fuel inflammation and alter the liver's metabolic responses. When researchers used gene editing or blocking enzymes to shut down SRC activity, inflammation dropped dramatically. The specificity of the effect suggested that blocking this single enzyme could be therapeutic.
What makes these discoveries particularly powerful is that they identify not just the problem but the precise molecular levers to pull. Neither FOXM1 nor SRC emerged from guesswork; both were found through rigorous examination of human tissue and validated in animal models. The two pathways appear to work in concert—one driving the structural damage and fibrosis, the other triggering the immune cascade that perpetuates it.
Dr. David E. Cohen, chair of Cedars-Sinai's Department of Medicine, emphasized the urgency: "These rigorous studies contribute greatly to our understanding of alcohol-associated liver disease. The findings could open new pathways for the development of urgently needed treatments." Tomasi noted that UBC9's role extends far beyond the liver, suggesting these discoveries could inform treatment approaches for cancer and other inflammatory conditions.
The research doesn't solve the problem overnight—these are preclinical findings, meaning they remain in the laboratory stage. But they transform alcohol-associated liver disease from a death sentence with no medical countermeasures into a disease with identifiable, druggable targets. For patients and families trapped in the cycle of addiction and organ failure, that distinction could mean the difference between despair and hope.