Unraveling Wnt Signaling in the Cartilage to Deal with Osteoarthritis.

Osteoarthritis is the most common joint disorder worldwide, for which no cure exists. Increasing evidence suggests that the Wnt pathway plays a critical role in this disease and may be an effective target for therapy. However, modulation of this cascade to safeguard cartilage health remains a challenge, as we fail to fully understand how it is regulated. My research program aims to dissect molecular mechanisms that control the Wnt pathway in cartilage, to develop Wnt-based therapeutic strategies for osteoarthritis. I will build on previous knowledge and experience by investigating factors that potentiate DOT1L, an enzyme we identified to be a key Wnt pathway modulator in cartilage. Furthermore, I aim to discover novel elements that modulate the effects of the Wnt pathway using innovative screening technologies, and I will build on strong preliminary data revealing novel interactions of the Wnt pathway with the Insulin-like growth factor system.