My research group has a long-standing interest in understanding the molecular mechanisms of cell adhesion and migration underpinning normal and pathological conditions, including inflammation and cancer. We focus on two families of molecules – integrins and kindlins. Integrins are heterodimeric transmembrane proteins that mediate cell-cell, cell-extracellular matrix, and cell-virus interactions. Integrin ligand-binding is regulated by its conformational change that is dependent on the interactions between its cytoplasmic domain and cytosolic proteins. These cytosolic proteins can either be positive or negative regulators of integrin function. Currently, my research group and in collaboration with others seek to define the molecular basis of cross-talks between these regulators, and how they modulate integrin ligand-binding, signaling and cytoskeletal re-modelling under normal and pathological conditions, such as chronic inflammation and cancer metastasis.

Kindlins are a small family of FERM-domain-containing cytoplasmic proteins. Three kindlin paralogs have been identified with dissimilar tissue expression profiles. Over the last few years, kindlins emerged as key regulators of integrin activation and signaling. The importance of kindlins is underscored by diseases Kindler syndrome, leukocyte adhesion deficiency III, and cancer. In addition to integrin-affinity regulation, our research group and others have shown that kindlins promote integrin clustering, which strengthens cell-ECM and cell-cell adhesion. There is also gaining evidence that kindlins are involved in cellular signaling conduits that are independent of integrins. We are investigating the roles of kindlins in these pathways in the context of cancer progression.