Research Topic:  Regulation of cell migration by cell-ECM adhesion and integrin signaling

Cell migration is essential for a variety of biological events including embryonic development, wound healing, inflammation and the metastasis of malignant cells. Our long-term goal is to understand the molecular mechanisms by which cell migration is regulated during these biological events. We focus on a family of cell surface receptors called integrins, which play critical roles in attaching cells to a substratum on which they migrate. One member of the integrin family, α4β1 (α4β1) integrin, is specifically expressed in migratory cells during embryonic development.

Our studies on mouse embryos deficient in the α4 integrin subunit revealed key roles of α4β1 integrin in the migration of epicardial progenitor cells on the heart and the distribution of vascular smooth muscle progenitor cells along developing blood vessels.  Work is in progress to elucidate how αβ1 regulates the motility of these cells.

By expressing α4β1 integrin in cultured cells, we have demonstrated that this integrin promotes directionally persistent cell migration via molecular interactions at the cytoplasmic domain of the α4 integrin subunit. Work is in progress to identify the intracellular signaling components that are downstream of α4β1 and understand how this cell adhesion receptor regulates directionally persistent cell migration.