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DOT1L: a key regulator of growth factor signaling pathways in the joint

Osteoarthritis is the most common chronic joint disease with enormous societal costs. In osteoarthritis, structure and function of the joints are gradually affected leading to pain and disability. Current treatment options remain limited and no specific disease modifying drug strategies are available. We have contributed to the discovery that DOT1L, an enzyme that modulates gene expression in the cell nucleus, plays a role in this disease. In this project, we aim to further study the role of DOT1L in joint health and disease and more in particular its effect on critical signals in cartilage and bone. We have a particular interest in the way DOT1L regulates Wnt signaling. This pathway has been previously associated with osteoarthritis. We will use a translational research approach using state-of-the art technologies in the analysis of patient derived cells and samples combined with innovative mouse models of disease. Our research plan aims to integrate these human and animal model data and to precisely define the DOT1L network and the opportunities it offers to identify new therapeutic targets.

Date:1 Jan 2016 →  31 Dec 2019
Keywords:DOT1L, key regulator, growth factor, signaling, joint, pathways