Steven E. Mansoor, MD, Ph.D., is among 72 scientists receiving a prestigious NIH New Innovator Award for his work to develop better drugs by understanding how they work at the molecular level. (OHSU/Christine Torres Hicks)
The work of an early-career Oregon Health & Science University physician and scientist to develop better drugs by understanding how they work at the molecular level has been recognized by the National Institutes of Health with a prestigious Innovator Award.
Steven E. Mansoor, MD, Ph.D., assistant professor of cardiovascular medicine and chemical physiology and biochemistry in the OHSU School of Medicine, is among 72 scientists receiving the NIH Director’s New Innovator Award, The NIH Common Fund’s High Risk, High Reward Research Program was announced today.
The New Innovator Award supports researchers who are within 10 years of their final degree or clinical residency, and who propose innovative, high-impact projects in the biomedical, behavioral or social sciences. As part of the award, Mansoor will receive $1.5 million in research funding over five years.
As both a health care provider and a researcher, Mansoor has one foot in the clinic, where he treats patients as a cardiologist at the OHSU Knight Cardiovascular Institute, and the other runs a basic science laboratory that is part of the Department of the OHSU School of Medicine. of Chemical Physiology and Biochemistry.
His research focuses on better understanding how drugs work at the molecular level, including how receptor proteins on the surface of cells recognize and respond to molecules. By understanding the molecular details of this process, Mansoor hopes to design drugs that can target specific receptors with greater precision and accuracy, and limit drug interactions with other cellular proteins that often cause unwanted effects.
“Trying to develop drugs that can really benefit my patients by limiting off-target side effects, that’s what got me interested in structural biology,” Mansoor said. “I hope that my research can make a difference to my heart disease patients as well as to the larger scientific community.”
In 2019, he led a study describing how a protein associated with numerous health problems works after observing it at the molecular level for the first time. Mansoor and colleagues used cryo-electron microscopy to obtain the 3D structure of the P2X7 receptor, an ion channel protein embedded in a cell’s membrane that allows electrically charged particles to enter a cell when activated.
Overactivation of P2X7 receptors has been associated with chronic inflammation, leading to plaque buildup in arteries, cancer metastasis, neurological conditions like Alzheimer’s, and more. With his new NIH funding, Mansoor will use the protein’s detailed structure to identify new molecules that can bind to the P2X7 receptor protein and deactivate it.
“Knowing the shape of the P2X7 receptor and how it works allows us to design new drugs that can control it,” he said. “If we develop a drug that can safely shut down its activity in blood vessels, we may be able to prevent the buildup of plaque in the arteries, also known as atherosclerosis. This drug would also reduce the progression of plaque buildup by to someone who already has existing atherosclerosis.”
Currently, there are no FDA-approved drugs that bind to the P2X7 receptor protein.
“Developing a new drug is ambitious,” Mansoor said. “I am grateful to have received this award, which allows me to carry out a high-risk, high-reward project. If we are successful, this project has the potential to pay dividends for many patients.”