Name: Matteo Calligaris
Tel. 091 6041480
Prof. Elisa Nuti
Dr. Simone Scilabra
PhD Project title
Studying iRhom2 as new potential therapeutic target in Osteoarthritis
Osteoarthritis (OA) is an articular joint disease which affects 250 million people worldwide. Due to these numbers, it has notable implication on the healthcare system and wider economic impact. The pathogenesis of OA is complex and comprises mechanical, inflammatory, and metabolic factors, which ultimately lead to structural destruction and failure of the joint.
iRhom2 plays a pivotal role in inflammation by regulating TNF alpha release. It has been seen that ablating its activity results in an improvement in several inflammatory condition such as sepsis, rheumatoid arthritis, lupus nephritis and metabolic disorders.
From our preliminary data, iRhom2 may control the function of proteins involved in the articular joint wreckage. We speculated that iRhom2 could be a potential therapeutic target for OA by tackling the disease from two different aspects: preventing chronic inflammatory condition and reducing joint degradation.
To fully understand the role of iRhom2 in the pathogenesis and development of the disease, the project relies on a highly collaborative network. The aims of my project are:
- Produce an inhibitor antibody using novel phage-display library (Nissim library) able to block iRhom2 activity and contrast OA development. This part of the project will be carried out at the Prof. Nissim lab at the William Harvey Research Institute at the Queen Mary University in London.
- Using state-of-art bioinformatic tools to develop small molecules from positive candidate of phage-display inhibitory antibody and validate possible compound to transfer in clinic. This part of the project will be undertaken in Prof. Nuti lab at the Department of Pharmacy in Pisa who has already developed several bioactive compound important in the field of OA.
- Use cutting edge technique of shotgun proteomics and biochemistry to bring to light the mechanistic role of iRhom2 in joint degradation. This part of the project will be undertaken at the Fondazione Ri.MED in Palermo under the supervision of Dr. Scilabra.
- Investigate OA development in surgical-induced mice model. This part of the project will be taken over at the Institute of Ageing and Chronic Disease at the University of Liverpool under the supervision of a leading researcher in the field of OA mouse model: Prof. Bou-Gharios.