Genetics and cell biology

Age related diseases

team-item

Head of Unit

Simone Cenci

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Research is focused on the biology of plasma cells (PC), terminally differentiated effectors of antibody responses, and their malignant counterpart, multiple myeloma (MM), and integrates hypothesis-driven and agnostic, wide- scope approaches (proteomics and metabolomics).

Research activity

The Unit is particularly interested in autophagy, a crucial asset ensuring proteome plasticity, across PC ontogenesis, in immunity, i.e., in the control of antibody responses and in the maintenance of serological memory, and in the pathobiology of MM.

Troubled protein homeostasis is an established stress phenotype of cancer that provides unexpected therapeutic specificity, with MM as the paradigm of proteasome inhibitor (PI) responsive cancers. After contributing to clarify the bases of the unique sensitivity of MM to PIs, the research group disclosed a novel, specific and essential function of autophagy in PC ontogenesis, required for the maintenance of the bone marrow memory PC niche, the normal counterpart of MM.

Next, the unit defined the protein and organelle-homeostatic functions of autophagy in MM, and identified a novel non-oncogene addiction of this malignancy to the prototypical autophagy adapter SQSTM1/p62 and unique organellar stress features in neoplastic PCs.

These discoveries provide a powerful framework for identifying new molecular targets against PC malignancies. Synergic studies on the skeletal microenvironment help explore the vicious relationship of MM with the bone marrow.