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UND Pushing the Boundaries of COVID-19 Research
North Dakota Ag Connection - 01/14/2022

A research team led by an assistant professor in the UND School of Medicine & Health Sciences Department of Biomedical Sciences, Abraam Yakoub, Pharm.D., Ph.D., has been awarded a five-year, $4.5 million award from the National Institutes of Health for a project proposal that has the potential to "push the boundaries" of research on COVID-19.

Yakoub and his team recently won the prestigious NIH Director's Transformative Research Award for their proposed work to demystify the disease mechanism of COVID-19 and help develop new therapeutics for it. Their project is titled "SARS-CoV-2 tropism in the brain and its relationship to COVID-19 pathogenesis."

"Why is the virus killing millions of people?" Yakoub asked. "Is it just a lung infection or something beyond? We told the NIH we have an idea why this might be happening, and they liked the idea. [This award] is a testimony to our exceptionally innovative, trailblazing research program. It means we really are thinking outside the box in order to crack a scientific mystery."

So creative is this concept that the NIH gave Yakoub a grant set aside for teams proposing "transformative" projects that "have the potential to create or overturn fundamental paradigms," as the NIH put it.

"The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known," NIH Director Dr. Francis Collins said of the Transformative Award winners in a notice on the NIH website. "These visionary investigators come from a wide breadth of career stages and show that groundbreaking science can happen at any career level given the right opportunity."

"It was heart-warming to be recognized by the NIH director ... that our work and ideas are indeed transformative -- a paradigm shift of the mainstream understanding of disease and biology," Yakoub added. "It was satisfying and shows that people understand how big these ideas are and that they could change the world."

Yakoub, a Harvard and Stanford alumnus and the principal investigator of the project, leads an ambitious team pursuing projects at the forefront of science and medicine. In the various projects of his research program, Yakoub employs cutting-edge concepts in biology, including genetic engineering, synthetic biology and gene therapy.

COVID-19 notwithstanding, Yakoub is receiving a second NIH grant allowing his lab to take a similarly creative approach to the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

"We're using synthetic biology and directed evolution to evolve a protein that will allow it to acquire a therapeutic function," he said. "While a major direction of my research program has to do with understanding why virus causes disease, another major direction is to actually turn that disease or the virus into a cure for other diseases."

As peer reviewers put it, the potential significance of Yakoub's gene therapy project is "tremendous." "This therapy has the potential to revolutionize the field," the reviewer said, adding that "if the aims are even partially successful, the project could lead to new therapeutic avenues for neurodegeneration."

The type of research that the Yakoub lab pursues is considered clinical translational research (CTR) in so far as it is research that "translates" discoveries made at the laboratory bench into novel therapeutics such as pharmaceuticals or gene therapies that directly will benefit patients in the clinical setting. The SMHS has made CTR a priority in recent years through an earlier grant supported by the NIH.

"We want to inspire our students to think innovatively, and part of my mission is to role-model to others thinking big," Yakoub said. "We want to inspire and urge students to think fearlessly and transformatively, to think outside the box, think boldly and not be afraid to challenge or overturn paradigms or a certain mainstream understanding that might be incomplete. We want to role model to our students how to develop the transformative mind."


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