WVU researchers explore mechanisms behind newly-discovered ciliopathy through international partnership with Swiss National Science Foundation

A grant awarded to the West Virginia University School of Medicine is helping faculty researchers partner with scientists from around the world to explore the mechanisms behind a newly-discovered form of the genetic disorders known as ciliopathies.

The grant was awarded to the lab of Rong Liu, Ph.D., assistant professor in the Department of Biochemistry and Molecular Medicine, by the Swiss National Science Foundation. It will provide more than $3.6 million in funding over four years, with approximately $800,000 being allocated to Dr. Liu’s lab to dissect the molecular and cellular defects caused by the disease-associated mutations.

Liu explained that nearly all cells in the human body rely on tiny, antennae-like structures called cilia to sense and respond to their environment. Genetic mutations can cause cilia to malfunction, affecting multiple major organs such as the eyes, kidneys, muscles and brain, and resulting in a group of disorders known as ciliopathies.

“Recently, our collaborators in Europe identified several unrelated individuals with a new type of syndromic ciliopathy caused by mutations in a previously unrecognized cilia-related gene,” Liu explained. “This project aims to determine how these mutations impair cilia function and ultimately lead to the disease.”

The four unrelated patients who were identified to be carrying this rare genetic mutation all shared similar symptoms, including vision loss, obesity, kidney abnormalities, polydactyly and various psychiatric symptoms.

Liu and her team will primarily focus on understanding why the mutant proteins fail to work properly by examining their structure and function as purified proteins. The team will utilize high-resolution live-cell imaging to observe how these proteins operate within the cilia in real-time and how their defective forms disrupt this process and lead to disease.

Liu explained that since ciliopathies involve complex, multi-system symptoms and can be caused by mutations in a wide variety of different genes, one of the major challenges in treating these disorders is making an accurate and timely diagnosis.

“By characterizing this newly-identified ciliopathy at the genetic, molecular and cellular levels and linking these findings to clinical symptoms, our research will provide essential information for recognizing and diagnosing this disease. In the long term, this clearer understanding can help guide more precise patient care and support the development of targeted therapies.”

The funding for this project will also provide training opportunities for learners at various stages at the School of Medicine, including undergraduate students, graduate students and postdoctoral researchers.

“While our work focuses on the basic science side, it also offers excellent opportunities for medical students and residents to explore fundamental research while also staying closely connected to its clinical relevance,” she said. “This integration helps trainees understand the disease from both molecular and clinical perspectives. Trainees will play an active role in designing and conducting experiments and will gain valuable hands-on training experience with advanced research techniques, including single-molecule imaging and high-resolution live-cell microscopy.”

Liu serves as one of four primary investigators on this project, which also includes Carlo Rivolta, Ph.D., from the University of Basel; Oliver Devuyst, M.D., Ph.D., from the University of Zurich; and Hoai Viet Tran, M.D., from the Jules-Gonin Ophthalmic Hospital.

The project is also supported by Neil Billington, Ph.D., director of the WVU Microscope Imaging Facility, who will provide critical expertise in advanced imaging techniques.

“This project has roots here at WVU,” Liu said. “The initial work in my lab that led to this collaboration was supported by the WVU Visual Sciences CoBRE Grant. Another key member of this team is Abigail Moye, Ph.D., a former graduate student in the WVU Department of Biochemistry and Molecular Medicine. She is now a postdoctoral researcher at the Institute of Molecular and Clinical Ophthalmology Basel in Switzerland and has played a major role in moving this international collaboration forward.”

To learn more about research opportunities in the Department of Biochemistry and Molecular Medicine, visit medicine.wvu.edu/biochemistry-and-molecular-medicine/research.