Our Research

Philip Marsden is a Clinician Scientist and Professor of Medicine at the University of Toronto. The Marsden lab is focused on understanding the contribution of endothelial cells to human health and disease. Endothelial cells form the inner lining of blood vessels and line the closed cardiovascular system.

Our lab is especially motivated toward understanding the contribution of important endothelial genes to diseases processes and novel aspects of how endothelial genes are regulated, especially by epigenetic processes. For instance, the cells are where they are exposed to blood flow, which exerts a frictional force known as shear stress. Regions of the vascular tree that experience uniform, undisturbed flow have high average shear stress and are less susceptible to atherosclerosis. In contrast, regions of flow oscillation and reversal, termed disturbed flow, have a lower shear stress rate and are more susceptible to atherosclerosis. ECs respond to changes in shear stress, in part, by changes in gene expression. We are studying the effects of varying flow patterns on long noncoding RNAs and DNA methylation pathways. These epigenetic, or chromatin-based, processes are exciting new areas for understanding how and where atherosclerosis occurs.

 

More recently, our lab is studying how blood flow and hypoxia interact in the biology of endothelial cells, especially whether post-transcriptional processes play an important role in blood vessel gene expression.

Our lab uses the BioSpherix Xvivo Model X3, CytoCentric Cell Incubation & Handling Platform for our in vitro hypoxia studies to control physiologic O2, CO2, and temperature conditions in studies with endothelial cells. We use this platform in order to avoid the uncontrolled variations which typically occur when cell cultures are transferred between conventional incubators and biological safety cabinets for handling. Learn more: https://biospherix.com/vascular-research/

X