Martin Lotz
Job Description
The theme of our research is to discover molecular and cellular mechanisms that are dysfunctional in musculoskeletal tissues during early stages of pathogenesis to create a foundation for therapeutic interventions to prevent disease onset and slow progression. Diseases of interest include osteoarthritis, meniscus injury and intervertebral disc degeneration.
Our general experimental approach is to analyze normal and diseased human tissues for changes in gene and protein expression. Genes and proteins that are differentially expressed are then tested for function using cell culture and mouse models. This allows for prioritization of genes and proteins as promising therapeutic candidates which are validated using genetic and pharmacologic approaches.
Our research interest is in joint biology, joint aging, arthritis pathogenesis, preclinical and clinical drug development.
Since 1989 Dr. Lotz directed a program on joint aging and osteoarthritis. Our studies identified aging-related changes in cartilage and other joint tissues that determine risk for osteoarthritis.
We discovered that cellular homeostasis mechanisms are compromised in aging and that this represents an early event leading to tissue damage.We initiated a ‘Joint Omics’ project which uses next generation sequencing technologies to uncover aging and disease associated changes in the transcriptomes in joint tissues. Data from this project are being used to identify key regulators of the abnormal phenotypes of cells, with focus on transcription factors.
Our current studies address the role of FOXO, KLF and MKX transcription factors and the circadian rhythm pathway in cartilage homeostasis and osteoarthritis pathogenesis. These transcription factors are also being investigated in meniscus, ligaments and spine. Efforts are ongoing to discover small molecules and genetic approaches to target transcription factors in the treatment of joint diseases and in tissue engineering.
