Elucidating the role of ANP32A as a key hub in osteoarthrithis

Osteoarthritis is the most common chronic joint disease world-wide and a major health concern. The host laboratory for this fellowship is focussed on understanding the mechanism that leads to loss of a healthy status in the joint, in particular in cartilage, the tissue that caps the bones and allows smooth movement. We recently identified the molecule ANP32A to play a very important role in health and disease of the cartilage. Loss of ANP32A function leads to osteoarthritis. However, we currently do not fully understand the events that control ANP32A levels in the cartilage. Understanding these processes is of great interest to develop therapies for the disease aiming at maintaining or increasing ANP32A levels. In this project we will specifically study mechanisms that control these levels using sophisticated and innovative analyses. In addition we aim to further understand the processes that are triggered when there is a lack of ANP32A. Importantly, our work will first be performed in specific model systems such as cell lines but then validated using cartilage samples and cells from patients with osteoarthritis. Finally, proof-of-principle will be provided for novel targets using dedicated animal models of the disease.