Research studies in our lab are primarily focused on a family of zinc-dependent proteases named A Disintegrin And Metalloproteases (ADAMs) with an emphasis on their role in cancer development, autoimmunity and inflammation-associated diseases. ADAMs can function as signaling scissors by cleaving and releasing the extracellular domain of several membrane-anchored proteins from the cell surface, as soluble proteins through a regulated proteolytic mechanism called ectodomain shedding. Examples of membrane proteins that are shed by ADAMs are the pro-inflammatory cytokine TNF alpha, L-selectin, the Interleukin-6 Receptor, and ligands of the Epidermal Growth Factor Receptor that drive disease processes including cancer progression and inflammation.

We have recently demonstrated that iRhom2, a proteolytically inactive member of the rhomboid family, controls the maturation of ADAM17 in myeloid cells, and that mice lacking iRhom2 have no evident spontaneous pathologies and are protected from TNF alpha-dependent septic shock.

Currently our lab is elucidating the pathophysiological role of iRhom2 and ADAM17 in chronic inflammatory diseases by taking genetic, cell biological, as well as immunological approaches. We anticipate that our studies will reveal interesting new insights into the role of iRhom2 and ADAM17 in cell-cell interactions and signaling. We hope that our studies significantly advance the understanding of iRhom2 and ADM17 function in chronic inflammatory diseases and underscore their potential as a target for intervention in modulating pathologies related to autoimmunity and inflammation.