The Rask-Madsen laboratory studies how endothelial cell dysfunction can contribute to the increased cancer risk in in obesity and diabetes.  This work has developed from an interest in how insulin resistance in vascular endothelial cells increases atherosclerosis and impairs angiogenesis.  Current work performed in the lab show how insulin resistance in endothelial cells increase tumor formation in a mouse model of intestinal tumor formation.  We use animal models with tissue-specific changes in gene expression and advanced cellular phenotyping by mass spectrometry and other methods.

Insulin resistance in endothelial cells profoundly alters endothelial cell function with increased leukocyte adhesion to endothelium due to increased expresson of vascular cells adhesion molecule-1 (VCAM-1) and other factors.  One focus of the lab is to identify novel molecular regulation of leukocyte adhesion to endothelial cells and to characterize how endothelial cell dysfunction in obesity and diabetes preferentially recruits subsets of leukocytes.

We also study the vascular niche for cancer stem cells.  These experiments use co-culture of endothelial cells and tumor organoids in 3D culture as well as characterization of the tumor stem cell population in intestinal tumors from mice with endothelial-specific genetic modifications.  Our aim is to discover proteins secreted by healthy and dysfunction endothelial cells with influence on stemness or differentiation of cancer stem cells.  Our long-term aim is to identify targets for reducing cancer risk in obesity and diabetes.