Laura Sommerville, PhD
Understanding the effects of von Willebrand Factor deficiency on pericyte function during angiogenesis
In patients with acquired or congenital von Willebrand's Factor (vWF) deficiency abnormal angiogenesis has been linked to development of vascular malformations in the gastrointestinal (GI) tract. Known as angiodysplasia, these lesions can be the source of severe bleeding and are often unresponsive to vWF replacement therapy, making them a significant unmet clinical challenge.
The first step in the process of angiogenesis is dilation of "mother vessels" from which new vessels will sprout. We have reported that vessel dilation is accompanied by loss of tissue factor (TF) expression from perivascular cells that encircle those mother vessels. TF remains absent from these pericytes throughout angiogenesis, but gradually returns as vessels mature and angiogenesis stops. Thus, immature angiogenic vessels are prone to bleeding.
We hypothesize that that the excessive vascularity and bleeding associated with vWF deficiency represents a failure of angiogenic vessels to mature normally, and as a result, pericyte stabilization of angiogenic vessels, and TF pro-coagulant activity, is lacking. The objective of this project is to determine how downregulation of vWF in endothelial cells affects the function and TF expression of pericytes during angiogenesis, and thereby help to elucidate mechanisms by which vWF deficiency spurs the development of vascular malformations.
Dr. Laura Sommerville graduated cum laude from Messiah College in 2004 with a BS in Biology, and received her PhD in Cellular and Molecular Physiology from Temple University in 2010. For her thesis project she determined how the scaffold protein, Allograft Inflammatory Factor-1, shapes the response of smooth muscle cells to vascular injury, and thus contributes to the development of vascular proliferative diseases. As a graduate student she also contributed to projects that aimed to characterize the importance of certain cytokines in physiologic angiogenesis. Through this work she developed an interest in the role of clotting factors in angiogenesis.
She was given an opportunity to follow this interest when she joined the laboratory of Dr. Maureane Hoffman as a postdoctoral fellow in 2014. There she took the lead on a project that focused on understanding the physiologic significance of tissue factor (TF) downregulation in pericytes during normal wound healing angiogenesis. With support from the National Hemophilia Foundation and Pfizer, Inc. she elucidated mechanisms and some of the critical signaling molecules that regulate perivascular TF loss. Now, as a Senior Research Associate in the Hoffman lab, she looks forward to utilizing the support from the Grifols Martin Villar award to expand the scope of her research to include the investigation of vWF as a potential regulator of pericyte function and TF downregulation during angiogenesis.
Laura Sommerville, PhD
508 Fulton St
Durham VA Medical Center
Durham, NC 27705
Tel.: 919-286-0411 x 3114