Abhijit S. Dighe, PhD, (left) and Charles R. Farber, PhD
The University of Virginia has been awarded a new $3.4 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to tackle one of the most pressing challenges in bone health: understanding the genetic factors that lead to osteoporosis.
The research, led by Charles R. Farber, PhD, professor and chair of the UVA Department of Genome Sciences, and Abhijit S. Dighe, PhD, assistant professor of genome sciences, will leverage cutting-edge genomic tools, including context-specific expression quantitative trait loci (eQTL), to uncover how subtle, genetically regulated changes in gene expression influence bone mineral density (BMD)—a key measure of bone strength and strong predictor of fracture risk.
Osteoporosis affects millions of Americans, leading to debilitating fractures and enormous healthcare costs. Although genome-wide association studies have uncovered hundreds of genomic regions linked to BMD, most of these regions fall outside of protein-coding genes. This makes it challenging to identify which genes are truly driving population-level variation in BMD.
The UVA researchers will apply state-of-the-art context-specific eQTL mapping—capturing how genetic effects on gene expression depend on cell type, developmental stage, and environmental conditions—together with single-cell transcriptomics and CRISPR-based functional screens to close this gap. Their goal is to move from statistical associations in the genome to clear biological mechanisms, ultimately revealing new targets for osteoporosis prevention and treatment.
The research team also includes Quanjun Cui, MD, and Michael Hadeed, MD, from UVA’s Department of Orthopaedic Surgery, who bring expertise in clinical orthopedics that will strengthen the translational impact of the project.
Filed Under: Research