Barry Rubin, MD, PhD, the 1998 Wylie Scholar, is currently the Division Head, Vascular Surgery at Toronto General Hospital in Canada.
What was your FAVR funded research?
The research in my lab focuses on two major areas: gene activation in the heart after vascular surgery, and the effect of sudden decreases in blood flow to the legs on muscle function and viability.
Following vascular surgery operations, mortality is generally low. However, the vast majority of patients who do not survive major vascular surgical procedures succumb due to heart problems rather than to problems directly related to the vascular surgery operation. This suggests that major vascular surgery operations may have an adverse effect on the heart. We have therefore explored the notion that major vascular surgical operations, or stress in general, causes changes in the way genes are expressed in the heart. For these studies, we are using advanced molecular biology techniques, including selective deletion of individual genes (so-called knockout mice). Once the pattern of gene changes in the heart following stress is delineated, potential targets for gene therapy that could decrease mortality following major vascular surgery could be identified and assessed for clinical efficacy.
Blood flow to the legs may be cut off by clots that break off from the heart and lodge in leg arteries, by progressive disease in the arteries of the leg (atherosclerosis), or by direct trauma to leg arteries. If blood flow to the legs ceases for an extended period of time and is then restored by surgery or clot busting drugs, the surge of blood flow into the leg causes further muscle damage and may cause the muscles to die. This is because the process of stopping and then restarting blood flow to the leg causes a massive inflammatory reaction in the leg, which can exacerbate muscle injury. We have been studying the mechanisms that cause muscle damage following cessation and subsequent restoration of arterial blood flow to the leg for many years. In our most recent studies, we have identified genes that appear to play a pivotal role in muscle injury. By inhibiting these genes, it may be possible to decrease the muscle damage that a patient sustains when blood flow to their legs is restored after prolonged episodes of decreased blood flow. These therapies could decrease muscle damage, improve leg function and decrease the amputation rate associated with acute cessation and subsequent restoration of blood flow to the legs.
What impact did the Wylie Scholar Award have on your ability to continue research?
The unfettered financial support associated with FAVR's award allowed me to continue funding of my research laboratory at a time in my career when I had not yet published scientific observations in high-profile basic science journals, and was therefore unlikely to attract support from National funding agencies. I am please to report that as a direct result of research that was funded by the Foundation for Accelerated Vascular Research through the Wylie scholarship, my laboratory published research articles in high impact journals such as Circulation Research, the Journal of Immunology and the Journal of Biological Chemistry (two), and attracted funding from multiple agencies, including the Physicians Services Incorporated Foundation of Ontario, the Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research. In fact, I am currently the only vascular surgeon in Canada to hold a 5-year operating grant from the Canadian Institutes of Health Research. Therefore, it is clear that receipt of the Wylie Scholar Award was a pivotal event in my development into a successful, peer-review funded, independent surgeon-scientist.
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