Research in Scilabra’s Lab, which currently comprises a post-doc, 3 PhD students and an MSc intern, is focused on elucidating the role of a class of membrane-tethered metalloproteinases, called ADAMs (a disintegrin and metalloproteinases), in health and disease. For their ability to release cell surface proteins, ADAMs are involved in a number of cellular processes, including cell-communication, cell-adhesion and molecular transport. Our lab uses a synergistic array of proteomic, cell biology, biochemistry and in vivo models to identify substrates of ADAMs, validate them by orthogonal methods and uncover functional consequences of their ADAM-dependent release in vivo.

In detail, our studies are mainly centered on elucidating new functions of ADAM17 and its essential cofactors, the inactive rhomboid-like proteins 1 and 2 (iRhom1 and iRhom2) by using mass spectrometry-based approaches. Among others, Dr Scilabra’s lab is currently testing the hypothesis that iRhom2 inactivation has beneficial effects on OA progression by a dual role in inhibiting the release of TNF (a proinflammatory cytokine promoting the expression of cartilage catabolic factors) and LRP1, and endocytic receptor that reduces levels of cartilage-degrading proteases(Fondazione Con il Sud, N. 2018-PDR-00799, 01/09/2019 – 01/03/2023 “iRhom2: a new therapeutic target in osteoarthritis?”). In addition, his lab has recently found a new ADAM17-independent function of iRhom2 in aiding the maturation of MHC class I molecules and it is currently testing whether this mechanism has functional consequences in the recognition of cancer cells by the immune system or allograft transplantation (Piano Nazionale di Ripresa e Resilienza – Italian Ministry of University and Research (MIUR), DOT 1720429, CUP B73D21009330006; “Dissecting the role of iRhom2 in the autophagy of MHC-I molecules to enhance responsiveness of PDAC to immunotherapy”).

Team