Mick Jurynec

Synovial joints (e.g., the knee, hip, shoulder, etc.) are under strain from constant use. Over the course of aging, these joints are prone to degradation, characterized by loss of joint space, degeneration of articular cartilage, and remodeling of bone and other joint tissues; the composition of synovial fluid and synovium are altered, chondrocytes undergo hypertrophy, and bone spurs (osteophytes) can form. It is clear multiple cell types of the organ are affected, likely due to disruption of the inter-tissue signaling networks that maintain joint health and structure. Pathological joint degradation is osteoarthritis (OA), a debilitating disease that affects over 32 million adults in the US. Not a single disease modifying OA drug is available. Although we can describe the alterations observed in the damaged osteoarthritic joint, we lack fundamental understanding of the pathways that regulate synovial joint health and maintenance. The key immediate challenge in the field is to understand the molecular and cellular pathways that pose vulnerabilities to OA and need to be targeted for effective therapies.

The primary focus of my lab is understanding the functions of genes underlying the onset and progression of osteoarthritis (OA). My lab uses a combination of approaches including human genetics, bioinformatics, and analysis of model organisms to elucidate the molecular and biological mechanisms that alter homeostasis of the synovial joint leading to development of OA.

Given that there are no treatments for OA, understanding the genes and pathways that contribute to the disease would have a major impact on the OA field and address a significant unmet medical need. My lab addresses a fundamental problem in the field of OA: the complex problem of identifying molecular and cellular pathways that confer susceptibility to OA. These genes and pathways are those that need to be targeted therapeutically. We take a unique approach of combining model organism genetics and human genetics with the unparalleled resources at the U of Utah (e.g., the Utah Population Database and the Utah Genome project) and have successfully setup a pipeline for genomic discovery and functional analysis.

Our approach reduces the genetic complexity of OA by studying families with dominant forms of severe or early-onset OA. These families allow us to discover very rare mutations with severe effects on the OA phenotype in order to find pathways that when disturbed have an all or none effect on OA. We then quickly test the function of these candidate variants in zebrafish or cell culture to identify high priority genes. We then use these high-priority candidates to create mouse models that contain human disease alleles. These mice are used to determine how the variant gene causes OA and they become preclinical models to test drugs to inhibit or activate the affected gene/pathway. Finally, we are developing tools and resources for high-throughput drug screens to develop disease modifying therapeutics for OA.