Balancing science and care for medical progress
By Darby Kendall
Navigating the worlds of research and patient care requires both precision and passion, and Steven E. Mansoor, M.D., Ph.D., finds fulfillment in this work as a physician-scientist. At the intersection of heartbeats and breakthroughs, Mansoor pioneers research that could revolutionize how we treat vascular and neurological inflammation.
Mansoor has always had a penchant for scientific exploration, but after getting his B.A. from Reed College, he was undecided what medical specialty to focus on. Then, eight years into his M.D.-Ph.D. training at OHSU, he had an experience that helped him home in on the field of cardiology.
“There were two fields, neurology and cardiology, that were the most interesting to me because they’re historically full of opportunities for research. When I was a medical student trying to decide what I wanted to do, I did a cardiology rotation, and I spent two weeks with Edward Murphy, a cardiologist at the VA and OHSU who’s now retired,” Mansoor remembered. “It just so happened that during those two weeks, the cardiology fellow was out of town, and there was no intern or resident on the team. It was literally just me and Dr. Murphy and on the first day. He said, ‘Steve, you’re getting promoted to fellow this rotation.’ I spent two weeks one-on-one with him, and it was an incredible experience.”
Those two weeks established Mansoor’s love of clinical cardiology, which he maintains to this day. His drive to still spend a fifth of his time at OHSU doing clinical work comes from his love of helping people, and the face-to-face interactions with his patients are a nice change of pace on Fridays after spending the rest of the week in his lab. Mansoor’s work as a health care provider also benefits from his research, as both roles play off of one another to inform his greater medical knowledge.
“In school, I heard the term ‘bench to bedside,’ and it resonated with me. The idea is you do work at the bench and discover things there, and eventually your discovery translates into something that helps people at the bedside,” Mansoor said. “Being a scientist makes me a better clinician, and being a clinician makes me a better scientist. They feed off of each other in a way that I think is unique, interesting and beneficial to both my research and to my patients. My medical training gives me an understanding of the biological basis of disease that helps inform and frame my scientific questions. And the scientist part of me helps me better explain things to patients in ways that they understand.”
Battling heart disease with basic science
When it comes to his research in the Mansoor lab at OHSU, he and his team use structural biology to fight heart disease. Currently, they focus on the basic science, studying the structure and function of ion channel proteins embedded in the membranes of cells, in an effort toward drug development. Recently, Mansoor and Adam Oken, B.A., a graduate student in his lab, published an innovative paper on the complete structure of the P2X7 receptor, a protein whose overactivity is linked to various health issues ranging from coronary heart disease to nerve pain.
“We think about it like a lock and a key. The lock is the shape of the receptor, and the key is the drug that unlocks or locks it,” Mansoor said. “We’re trying to design keys that will fit into the specific part of a receptor, to lock it in place and prevent it from turning on, or to bind to it and open it. My research in a nutshell is trying to understand at a molecular level how these proteins work, so we can design drugs that effectively control them.”
Now, Mansoor is collaborating with scientists in Europe to study how a drug they have developed together affects inflammation in mice. So far, results are promising when it comes to suppressing neurological inflammation, and Mansoor is hopeful this will apply to the vascular system as well.
“Hopefully we can design a key that only fits the P2X7 lock, because many times when people take a drug, it is effective, but it has off-target effects where it interacts with other receptors to produce unwanted side effects,” Mansoor explained. “This drug we have developed seems very selective. My collaborators are seeing some very profound and interesting effects from the drug when used in mouse model of Alzheimer’s disease; specifically, the cognitive function of the mice improves. Their memory improves, and there’s decreased tau protein in the brains of these mice, and that tau protein is a marker of Alzheimer’s disease. Going forward, my plan is to study the drug here in Oregon and get it into some translational applications for cardiovascular disease.”
Support leading to success
The Mansoor lab opened at OHSU in 2020 in the midst of the COVID-19 pandemic, a time of uncertainty not only for the whole country, but for NIH-funded scientists and the medical field as a whole. Mansoor credits philanthropy for allowing him to reach his goal of starting his own lab, particularly support from the Silver Family Excellence Award. Before receiving the award, Mansoor only had enough funding from the NIH to either purchase equipment or hire people for the lab, as his OHSU-provided establishing funds were temporarily put on hold due to the pandemic, but the philanthropic funds allowed him to immediately start doing both. Beyond helping him build the foundation for his lab, Mansoor is grateful for philanthropy because of the flexibility it allows his research, like the studying of the P2X7 receptor.
“Oftentimes NIH funding is encumbered, whereas donated money is unencumbered. Having access to unencumbered funds lets you try things that you ordinarily might not be able to do. For example, when the scientists from Europe approached me back in 2020 to start trying to develop these drugs, the source of my funding wasn’t for that project, but because I had some of this flexible money, I said, ‘Of course, that’s what I want to do,’” Mansoor said. “You’ve got to have the courage, and you’ve got to have the funding. You’ve got to have the backing to be able to try something brave, try something out of the box.”
Over the years, Mansoor has also had several individuals he’s met through OHSU donate to his research program, further building the bridge between his medical and scientific work. “Steve Janik and Sheryl Manning, Randy and Barbara Lovre, and Barbara Allen and Jim Batzer have all provided me with generous support,” Mansoor said. “Presently, all my grants fund the basic science that is underpinning the drug development, but none of them fund the next steps. With this philanthropic support, I can do the preliminary experiments that are necessary to apply for larger NIH grants to do the translational work in animals. It really, really helps.”
Beyond expressing gratitude for the philanthropy that has backed his lab, Mansoor is thankful for the professional support he’s received at OHSU over the years. Working as a physician-scientist takes a lot of time and energy, and Mansoor says the assistance he’s received from mentors and colleagues along the way is invaluable.
“If it weren’t for all the people helping me, I could never succeed, especially trying to balance the physician-scientist life. Fortunately for me, the leadership at the Knight Cardiovascular Institute is supportive of physician-scientists,” Mansoor said. “Many places would rather just have clinical cardiologists who exclusively treat patients, because clinical cardiologists are so critical to making a medical institution successful. I am giving up something objectively important to the institution by spending 80% of my time doing research instead of seeing patients. I’m not strictly a scientist, and I’m not strictly a clinician. I’m something different, and I bring something slightly different to the institution. It takes a special leader to be able to see what that value is. I’m lucky in that sense.”
