Author: Brian Walcott
In recent years, advances in the management of cerebral arteriovenous malformations (AVMs) have been achieved across all available treatment modalities, from microsurgery to endovascular embolization to radiosurgery. However, AVMs are still associated with a significant potential for morbidity and mortality in a generally young and otherwise healthy population. This disparity is what fueled my motivation to pursue advanced clinical training in microsurgery and endovascular surgery, and to continue investigating the underlying pathophysiology of these lesions. The Christopher Getch Fellowship provided me with the resources I needed to set up and carry out experiments addressing this orphan disease.
Under the mentorship of Dr. Michael Lawton (University of California, San Francisco), I began to explore the genetic basis of AVMs on a more comprehensive level than ever done previously. To date, we have collected and performed whole exome sequencing of over 40 specimens from patients with sporadic AVMs. By analyzing AVM tissue obtained in the operating room with matched peripheral blood samples from patients, it was possible to eliminate most of the genetic “noise” that comes from variations in DNA found between different individuals. Since the exome is just a small portion of the total genetic material, further characterization with whole transcriptome sequencing is underway to determine if the way various genes are expressed or arranged may be a causative factor in AVM pathogenesis. It is my long-term plan to use information gained by these analyses to create more relevant animal models, with the ultimate goal of discovering a drug for AVMs that can be brought to clinical trial in humans.
As a recent residency graduate, the Christopher Getch Fellowship has been instrumental in accelerating a research platform I can carry into the future as a clinician-scientist. The substantial funding provided by the award goes beyond seed money—it has directly led to results that expand our understanding of the causative molecular mechanisms in AVMs.
BY ANALYZING AVM TISSUE OBTAINED IN THE OPERATING ROOM WITH MATCHED PERIPHERAL BLOOD SAMPLES FROM PATIENTS, IT WAS POSSIBLE TO ELIMINATE MOST OF THE GENETIC “NOISE” THAT COMES FROM VARIATIONS IN DNA FOUND BETWEEN DIFFERENT INDIVIDUALS.
Dr. Brian Walcott is currently a vascular neurosurgery fellow and clinical instructor at the University of California at San Francisco School Medicine in the Department of Neurological Surgery. He is a native of Maybrook, NY, and graduated from Loyola University Chicago School of Medicine. He completed his neurosurgery residency at Massachusetts General Hospital, where he spent two years as a post-doctoral research fellow in the Cardiovascular Research Center, developing zebrafish models of cerebrovascular disease. Following residency, he joined the department of neurosurgery at Massachusetts General Hospital as an attending neurosurgeon and was appointed as an instructor in neurosurgery at Harvard Medical School.