Earlier this year, Mohamed Zayed, MD, PhD, an Associate Professor of Surgery, Radiology, Molecular Cell Biology, and Biomedical Engineering in the Section of Vascular Surgery, and his team in the Zayed Lab received funding from the National Heart, Lung, and Blood Institute (NHLBI) for a new research project grant.
The R01 grant will fund a new line of investigation on how lipid synthesis by arterial tissue can impact peripheral atherogenesis, or the formation of fatty plaques in the arteries, in the setting of diabetes. The Zayed Lab has developed a unique model to study this disease process with the Division of Endocrinology, Metabolism and Lipid Research at Washington University School of Medicine.
Zayed’s team received a 5th percentile score for this grant, funding $2 million over a 4-year period. A small minority of submitted grants receive this kind of funding.
The goal of this research is to provide industry partners viable molecular targets to develop novel treatment strategies that can help prevent disease progression in patients with diabetes and peripheral arterial disease.
Over 10 million individuals with diabetes suffer from end-stage complications related to peripheral arterial disease. Peripheral arterial disease can happen in any blood vessel, but it is more common in the extremities. When a blockage happens in an extremity artery, the limb suffers, and that can ultimately lead to wounds, ulcers and amputations.
Amputation rates for patients with diabetes remain stubbornly high, Zayed explains, even with ongoing medical management. Diabetes is a very common disease and is becoming more prevalent in the United States, with almost 30% of the American population having diabetes or prediabetes.
“Preadolescents and adolescents are developing prediabetes at an earlier age, and so we expect the prevalence of diabetes to continue to increase,” says Zayed. “Along with that, the amount of peripheral arterial disease or blockages in extremity arteries are also going to also increase.”
Currently, vascular surgeons at the School of Medicine burrow through these blockages, open them up with balloon angioplasty and expand the vessel from the inside or put a stent or a scaffold to keep the artery open. This creates a new route to go past the blockage and still supply oxygen and nutrients to the limb.
Unfortunately, in patients with diabetes, it turns out that these procedures are often less effective.
“Many patients that have diabetes get these operations and they still end up having significant complications,” Zayed explains.
“We currently have nothing that treats the underlying disease process. Why is it that patients with diabetes are more prone to developing peripheral arterial plaque and difficult to treat blockages? We currently do not know that answer. And that’s what this grant is aiming to investigate,” Zayed states.
By targeting this disease process, the Zayed Lab team hopes to develop new and effective ways to treat these patients with diabetes and lower amputation rates.
“We want to make an impact on these patients’ long-term health and ability to function independently,” says Zayed. “When a patient gets an amputation, it’s a big transformative life altering event. They lose their autonomy, they lose their independence, they lose their ability to take care of themselves. If we can make an impact in preserving vascular health inf patients with diabetes, that would be highly impactful. Not for just the patients, but for society in general.”
It Takes a Village
One of Zayed’s key mentors at Washington University has been Clay Semenkovich, MD, Chief of the Division of Endocrinology, Metabolism and Lipid Research. This new grant is collaborative between the Zayed Lab and this division, as several of the endocrinology staff are coinvestigators on this project. Zayed credits this multi-disciplinary approach as a key factor in how they were able to get the funding.
“As a vascular surgeon I am not a diabetes specialist,” Zayed states. “One of the first things that I did here was to try to identify a mentor who is a diabetes expert, and Clay was perfect for this fundamental role.”
Zayed believes this kind of development would not be achievable unless you have multi-disciplinary expertise: “Science needs to be collaborative.”
Zayed is also incredibly grateful for his team at Washington University. Receiving this grant takes a village approach, he explains, and he was able to cultivate an excellent team from both an administrative and laboratory standpoint.
“It would not be possible without their work. I sit here and get to take credit for it, but in all honesty, it’s not a one-person show. It’s truly a group effort, we just happen to have a really good group of individuals that we get to work with on a day-to-day basis.”
Research That Hits Home
Zayed knew early in his career that he wanted to conduct research. He came to Washington University on a scientific investigator pathway, meaning he dedicates part of his professional effort to build a research program. He was passionate to start in terms of treating patients with diabetes and peripheral arterial disease because he’s had family members who are diabetic and had seen this problem require amputations in clinical practice. Furthermore, one of the Zayed Lab members had a direct family member that was diabetic that ended up receiving an amputation, so this is something that hits home for his team as well.
“I knew up front that this was what I was passionate about clinically, and I wanted to develop a research program on this topic,” Zayed says. “I came here with the premise that I would dedicate at least 50% of my time here at Wash U to developing a research program that would ultimately care for both patients that have diabetes and peripheral disease but also to develop, hopefully new technology that can better evaluate and treat them.”
Grants the Zayed team has received have been of great value and have allowed them to build the framework necessary to be able to do this type of research. Within the first couple of years that Zayed was at Washington University, he received the Wiley Scholar Award, which is given to one vascular surgeon per year in North America. This catalyst award gave the Zayed team funds to be able to develop infrastructure programs, including the Vascular Surgery Biobank.
Washington University has played an integral role in Zayed’s life as a surgeon-scientist. As the second most funded department of surgery in the country, Zayed feels supported in all his research endeavors.
“Wash U is one of the unique places in the country that values the contributions of surgeon-scientists in research and development, and our department is one of the most highly funded in the country,” says Zayed. “By supporting academic endeavors, surgeon-scientists can address key knowledge gaps and make impactful discoveries that help make patient lives better.”
Before Zayed decided to become a surgeon, he knew he first wanted to be a scientist. His father was a scientist at University of California, Berkeley and Zayed visited his lab there frequently as a child. From an early age, Zayed enjoyed being in a lab setting and being around the other scientists.
“It was interesting to be in that environment with scientists discussing research, new ideas, and ongoing experiments. It was collaborative, and I just found that atmosphere very lively and collegial,” Zayed explains. “When I was finishing college, my intention was to pursue a PhD and ultimately, run a lab at some point.”
Zayed’s path began to change after his father had a heart attack during his first year of college. This event stunned Zayed and his family, and they spent a week in the coronary care unit in a small town in New Hampshire.
Witnessing the medical team care for his father made a significant impact on Zayed. “It was amazing to see the high level of care nurses and doctors provided to save my father’s life,” he states. “They performed a procedure called atherectomy, which at the time was considered to be new and highly innovative. Now this is something I routinely do in my practice to treat patients with peripheral arterial disease.”
After the experience, Zayed came back to college and switched his major to pre-med, deciding that he wanted to do medicine. However, he did not give up on his scientific pursuits. When he went on to medical school, he did it as a combined MD and PhD medical scientist training program. This ultimately gave him the training to develop a research program on his own when he became faculty.
“Our experiences are certainly what shape the course of our lives. Sometimes unexpected events are what ultimately shape our future. For me, I am glad this led me to the career I am currently pursuing.”