“A Multicellular Model Reveals Defects Leading to Cerebral Cavernous Malformation” 

Denis Tsygankov, Ph.D.*
Research Assistant Professor
University of North Carolina at Chapel Hill

Seminar will be made available via videoconference in the Health Sciences Research Building, room E 160 and Technology Enterprise Park, room 208.

Cerebral Cavernous Malformation (CCM) develops in about 0.5 percent of the population worldwide. It is caused by mutations in one of three genes ccm-1, -2, or -3 that lead to enlarged leaky blood vessels. If this happens in the central nervous system, people experience seizures, paralysis, bleeding in the brain, and loss of hearing or vision. To understand the defects that lead to loss of proper tube formation in CCM patients, we developed a computational model for endothelial cells that takes into account their interaction with the extracellular matrix and each other through the extension and retraction of protrusions. The model also allows for the movement and change in shape of individual cells in response to forces exerted by neighboring cells. Our simulations not only reproduced experimentally observed tube formations of both wild type and CCM knockdown cells, but also captured  differences  between the behavior of CCM1 and CCM3 deficient cells, providing mechanistic insight into the distinct roles of these proteins. Our model predictions have been confirmed by various experimental measurements including next-gen RNA sequencing and live cell imaging.

Faculty Host: Eberhard Voit, Ph.D.