Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease across the globe. One major risk factor of NAFLD is obesity, which approximately 36% of Kentuckians face, according to America’s Health Rankings.

While diet and exercise may help address the underlying condition of NAFLD, they do not necessarily achieve satisfactory results in treating the disease.

Shuxia Wang, MD, PhD, professor of pharmacology and nutritional sciences at the UK College of Medicine, recently received a $2.4 million National Institutes of Health (NIH) grant to study how NAFLD develops and progresses. With this new grant-funded project, Dr. Wang hopes to find a more reliable, effective treatment.

“Currently, there is no NAFLD therapy. An effective alternative strategy is urgently needed,” Dr. Wang said.

NAFLD encompasses a range of liver conditions affecting patients who drink little to no alcohol. These include non-alcoholic fatty liver and non-alcoholic steatohepatitis. The main characteristic of NAFLD is excess fat in liver cells. Without proper intervention, it may progress to life-threatening conditions such as cirrhosis and liver carcinoma.

Using state-of-the-art technology including scRNA sequencing and tissue-specific knockout mouse models, Dr. Wang’s lab discovered that thrombospondin (TSP1), a secreted matricellular protein, impacts macrophage pro-inflammatory activation and NAFLD progression.

With recent funding from the NIH, Dr. Wang and her team will investigate a novel mechanism underlying NAFLD progression and test a novel therapeutic application of a peptide-nanoparticle to potentially block TSP1’s “detrimental effect” on NAFLD.

Knowledge gained from the project could lead to new treatment strategies for NAFLD that is associated with obesity.

Dr. Wang’s grant is funded specifically by the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK), which is housed within the NIH. The grant will fund the project through July 2027. During that time, it will support postdoctoral fellows and provide numerous learning opportunities for undergraduate and graduate students.

Dr. Wang leads this project alongside co-investigators Eun Lee, MD, (pathology and laboratory medicine) and Mariana Nikolova-Karakashian, PhD, (physiology) from the UK College of Medicine; Sheng Tong, PhD, from the UK College of Engineering; and Steven Weinman, MD, from Kansas University Medical Center.

With more than 50 publications, Dr. Wang maintains an expansive portfolio of research on obesity and its associated metabolic disorders including NAFLD, chronic inflammation, and insulin resistance. She has led and contributed to groundbreaking studies in these areas at the University of Kentucky for 17 years.