Michael J. Jurynec, PhD

Research Statement

My group works to discover and understand the functions of genes underlying the onset and progression of osteoarthritis. We use a combination of approaches including human genetics, bioinformatics, and model organisms (zebrafish and mouse) to elucidate the molecular and biological mechanisms that lead to changes in the synovial joint and contribute to the osteoarthritis phenotype.

Osteoarthritis (OA) is a common debilitating disease involving abnormal remodeling of joint tissues, severely reducing quality of life as a consequence of joint pain and limited mobility. It is the major cause of disability among adults. No cure for OA exists, and with the exception of surgical intervention, therapies tend to be solely palliative, failing to prevent the initiation or progression of the disease. Lack of basic scientific understanding of the genes and biological processes underlying or conferring susceptibility to OA is a key limitation to the development of effective therapies.

Analysis of families with highly penetrant, often severe, forms of osteoarthritis is a powerful approach for finding disease-causing variants. Deciphering how a human disease-associated variant affects gene function and leads to the disease state is a limiting step in understanding the genotype-phenotype correlation. Our recent work highlights the importance of combining human genetics with functional analyses in models. We identified gene variants associated with an inherited severe early-onset form of osteoarthritis. Analysis of the action of the gene in zebrafish embryos revealed the variant to be an activating mutation affecting the inflammation response pathway. These studies highlight inflammatory pathways as potentially important mechanisms driving the pathogenesis of osteoarthritis. Current work is aimed at testing whether the inflammation gene variant is sufficient to confer susceptibility to OA in mice and expanding the family studies to identify new gene variants and biological pathways that have strong effects on the pathogenesis of this disease.