The Lawton laboratory investigates the pathophysiology and hemodynamics of arteriovenous malformations (AVMs) and aneurysms. Aneurysms and AVMs are both a leading cause of stroke due to subarachnoid hemorrhage (SAH) and intracranial hemorrhage (ICH). Hemodynamic forces are known to be involved in the formation, progression, and rupture of these dangerous vascular lesions. The exact vascular biology initiated by hemodynamic forces and involved in the degradation leading to tissue rupture remains undefined. Dr. Lawton’s research combines basic science methodology with clinical data to study the proteins and genes found in human tissue. By identifying biological factors directly localized to AVM and aneurysm tissue, Dr. Lawton can also identify potential therapeutic approaches. In addition to studying vascular biology, anatomical studies of the cerebrovasculature, brain, and skull are performed to optimize complex surgical procedures.
Current Research Projects
Inflammatory Oxidative Stress in Cerebral Aneurysms
The pathogenesis of aneurysms remains undefined. Some aneurysms are stable and others evolve to a dangerously thinned vessel wall that easily ruptures, causing subarachnoid hemorrhage (SAH), a clinically devastating event. Our project aims to better understand the involvement of inflammatory oxidative stress in aneurysm wall degradation and, in collaboration with the UCSF Vascular Imaging Research Center (VIRC), to develop patient-specific tools to clinically predict the unstable thinned vessel wall. Human aneurysm tissue collected during surgical repair is compared to normal tissue, clinical outcomes, and patient-specific radiological scans. A growing body of evidence suggests that wall shear stress (WSS) (the friction between flowing blood and the vascular endothelium) is related to aneurysm remodeling and rupture. Vascular endothelial cell injury and dysfunction precede inflammatory cell infiltration and activation, as well as cytokine release. Inflammation increases reactive oxygen species (ROS) production and ROS promotes overexpression of matrix degradation by matrix metalloproteinases (MMP’s). Biological markers found localized to damaged or thinned aneurysm walls are matched to patient-specific hemodynamic data to work towards developing a predictive patient specific tool aimed to improve clinical care.
Comparison of anatomical and clinical exposure in cerebrovascular surgical approaches to optimized surgical outcomes
Using pre- and postoperative radiological imaging, intraoperative video, and images, morphometric comparison of anatomical and clinical patient data is performed to determine the benefits of standard approaches compared to alternate or optimized surgical approaches for cerebrovascular lesions. Prior to surgical dissection, we prepare anatomical specimens using Rhoton’s cerebrovascular colored-silicon injection of cadaver specimens. Once anatomical specimens are surgically dissected using the selected approach, anatomical data is compared to alternate anatomical surgical approached and clinical data from surgical cases. A variety of factors that effect patient outcome, such as brain shift, edema, field of view, and degree of retraction of brain and vessels are studied. Benefits of standard approaches are compared to alternate or optimized surgical approaches to systematically optimize patient care.
Radiation effects on transgenic arteriovenous fistula
An abnormal direct connection of an artery to a vein can be accomplished by surgical anastomosis to mimic flow conditions similar to an arteriovenous malformation (AVM). Under normal conditions arteries supply tissues with oxygen and nutrients via capillaries. These tissues drain into the venous system and are returned by veins under low flow. AVMs fed by arteries form high flow connection to veins, with a propensity for rupture and sequential hemorrhage. Radiation therapy is used to stop blood from shunting through the AVM by inducing cellular hyperplasia, consequently minimizing or eliminating the risk of rupture. However, this is often an incomplete treatment with a 3-year latency to achieve therapeutic effects. To discover distinct effects of radiation on genes of interest, our lab developed a xenographic transplantation rodent model employing radiated transgengic tissue integrated into a host animal, which replicates the angio¬architecture and hemodynamics of a simple AVM.