Qingzhang Zhu, Ph.D., assistant professor in the division of endocrinology, has recently received an R01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Zhu received over $2.8 million for his project "Target PAQR4-Ceramide-GPNMB Pathway in MASH."
An estimated 33.7% of U.S. adults have metabolic dysfunction–associated steatotic liver disease (MASLD), and about 6% (14.9 million) have progressed to metabolic dysfunction-associated steatohepatitis (MASH), a more serious form of the disease.
MASH is closely linked to obesity and other metabolic health problems. Over time, it can cause liver scarring, cirrhosis and liver cancer. Despite its growing impact, doctors still have limited treatment options and lack reliable, noninvasive tests to detect and monitor the disease. Scientists are increasingly focusing on ceramides, a type of active lipids that can build up in the liver and contribute to insulin resistance and liver damage. However, it’s still not fully understood what controls ceramide levels or how these lipids cause damage inside liver cells.
Zhu's funded project will investigate how these lipid molecules can contribute to liver damage when they become imbalanced and how they might drive the progression of MASH and liver fibrosis. The research will focus on PAQR4, a newly identified regulator of ceramide levels that may play an important role in disease development. By uncovering how PAQR4 controls ceramide balance and the downstream signaling pathways in the liver, the project aims to provide new insights into the biological mechanisms underlying MASH and liver fibrosis.
The findings could also reveal promising new therapeutic targets and biomarkers for chronic liver diseases, as well as other conditions associated with ceramide imbalance, including obesity and diabetes.
"Receiving this grant is a meaningful recognition of our research and an important opportunity to move work forward," Zhu said. "It gives us the resources to explore an important question in liver disease and to pursue findings that could ultimately benefit patients. For me, it is also a reminder of why this work matters. MASH and related metabolic diseases affect many people, and we need better ways to understand, diagnose and treat them. I am grateful for the support and excited about what we can accomplish with this funding."
Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK148764. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.