San Raffaele Telethon Institute for Gene Therapy

Pathogenesis and treatment of immune and bone diseases


Head of Unit

Anna Villa


To dissect mechanisms underlying autoimmunity, this Unit studies genetic defects characterised by infections and autoimmunity. Different diseases ranging from defects in RAG molecules or in genes involved in actin cytoskeleton remodelling (Wiskott-Aldrich syndrome, WAS) or defects associated with thymic abnormalities, are the main topics of the lab.

Research activity

The group is focused on the contribution of defective thymic cross-talk to the pathogenesis of autoimmunity in various diseases and how emerging regenerative therapies may remodel thymic architecture and T cell development. To this end, the combination of cell/gene therapy and regenerative medicine represents an innovative therapeutic approach to treat primary and secondary thymic defects.

Immunedysregulation and platelet defect will be studied in WAS with the final aim to dissect the contribution of B and Platelets to the pathogenesis of the disease. To this end, researchers are evaluating the efficacy of LV-mediated gene therapy (GT) currently ongoing at SR-Tiget.

Finally, studies are ongoing to evaluate the feasibility and efficacy of lentiviral mediated gene therapy of a severe bone defect due to alterations in osteoclast function. Autosomal recessive osteopetrosis (ARO) is caused by mutations in genes involved in the differentiation or resorption activity of osteoclasts, leading to death in the first decade of life. Lentiviral vector gene therapy is under development as alternative strategy, relying on peripheral blood (PB) CD34+ cells as the source of autologous hematopoietic stem and progenitor cells (HSPC). This group has developed a lentiviral platform that will be tested in the spontaneous mouse model, the oc/oc mouse and in CD34+ cells obtained from patients. These studies will be performed in parallel with analysis of the roles played by osteoclasts in the bone marrow niche.