Our research focuses on the role and regulation of a novel signaling complex nucleated by the protein KRIT1, a central regulator of cell adhesion and cellular quiescence. KRIT1 is a scaffolding protein that binds to critical protein regulators of cell adhesion and inflammation. Human patients with heterozygous loss-of-function mutations in KRIT1 are susceptible to the vascular disorder, Cerebral Cavernous Malformations. We were the first to identify a function for the KRIT1 complex in confluent endothelial cells, where it is required for junctional stability downstream of active Rap1 (Glading et al 2007). Our work continues to investigate the mechanisms of action of KRIT1 in the endothelium, however, as KRIT1 is ubiquitously expressed, we are also pursuing the role of this protein in cell-adhesion signaling in a number of cellular contexts, including hematopoietic cells and cancer. We use a wide variety of approaches in the lab to address these critical scientific questions, including advanced microscopy techniques, viral expression, transgenic animals, intravital microscopy, flow cytometry, and basic biochemical and molecular biology techniques.
- Crosstalk between inflammatory signaling, angiogenesis and cell-cell contact in vascular development and cancer.
- Role of extracellular matrix modification in the development of CCM.
- Structural and protein-protein binding interactions regulating KRIT1 localization and function.
- Role of KRIT1 in neutrophil and macrophage adhesion and migration.
For more information on current projects, contact Dr. Angela Glading.