‘Poking and prying with a purpose’

That’s medical research, the grants for which continue to set records at UND’s School of Medicine & Health Sciences

This story is drawn from material that originally appeared in For Your Health, the newsletter of the UND School of Medicine & Health Sciences.

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As the temperatures rise across North Dakota this spring and students start their summer break, a number of research projects at the UND School of Medicine & Health Sciences also are warming up.

Several SMHS faculty have been awarded research grants in recent months, allowing researchers at the school to dive into several new and continuing projects, including studies on breast cancer, Lyme disease, the neurological effects of allergies and more. Here is a brief roundup of research projects ramping up now:

• Congratulations to Holly Brown-Borg, Chester Fritz Distinguished Professor with the Department of Biomedical Sciences at the UND SMHS, who has been awarded a five-year, $3.5 million grant from the Hevolution Foundation for a project titled “Cellular mechanisms of frailty onset.” This project focuses on the underlying aging biology that leads to age-related dysfunction and disease.

“This five-year award will support research focused on defining mechanisms that contribute to the onset of frailty,” Brown-Borg noted, adding that the award is affiliated with her collaborator, Dr. LoDora Thompson, at Boston University. “Our project is aimed at determining the underlying factors that initiate muscle dysfunction with age. Once we determine the onset of the decline, we will study the mechanisms contributing to muscle dysfunction and then intervene by treating mice with a natural compound shown to reduce inflammation.”

Her hope, added Brown-Borg, is that the project will demonstrate that the decline in physical and muscle function with age can be delayed or prevented, leading to healthier life.

• Motoki Takaku, an assistant professor in the Department of Biomedical Sciences, was awarded a four-year, $792,000 award by the American Cancer Society to continue his study of breast cancer. Takaku’s laboratory uses a combination of genomics, biochemistry and gene editing techniques to study the basic mechanisms and cancer-specific functions of the components of cells that regulate the protein-DNA complex known as chromatin.

“Approximately 30,000 new cases of invasive breast cancer in the U.S. each year will carry mutations in the gene called GATA3,” said Takaku, who has been studying the GATA3 gene for several years. “Our project aims to identify the roles of GATA3 mutations in breast cancer, and this award will stimulate our research activities. GATA3 mutations are frequently found in metastatic breast tumors, and we think the results from this project will have a significant impact on the breast cancer community.

“We hope we will eventually find a strategy to target GATA3-mutant metastatic breast tumors.”

• Likewise, Alexei Tulin, professor in the Department of Biomedical Sciences, was awarded a $740,691 grant from the National Science Foundation to fund a project that extends his laboratory’s focus on the function of “PARP1” (specifically, poly(ADP-ribose) polymerase 1), a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability and cell death.

“The goal of this research is to use the Drosophila – or fruit fly – system of PARP1 metabolism as a model to investigate how any cell can undergo quick, local and reversible chromatin reprogramming, fine-tuning the induction of local gene activity,” explained Tulin. “Understanding how PARP acts within normal, undamaged chromatin will advance our knowledge of gene regulation and facilitate the possible development of new drugs and methods to reprogram genes involved in certain health conditions.”

• For her part, Kumi Nagamoto-Combs, assistant professor with the Department of Biomedical Sciences, recently received a $30,000 Early Career Scholars Program Award from UND’s Division of Research and Economic Development for her collaborative project with Bo Liang, from the UND Department of Biomedical Engineering, for a project titled “A window into the mind: monitoring the activities of intracranial immune cells.”

As Nagamoto-Combs put it, she and Laing “plan to track immune cell trafficking in the brain,” in an effort to establish a novel imaging system by which the activities of immune cells within the central nervous system can be visualized and monitored. “Upon completion of the project, we intend to use the resulting imaging and histological data for submitting a National Institutes of Health R01 grant application or equivalent to further continue our investigation.”

Such news comes on the heels of Nagamoto-Combs receiving the second-year portion – $370,791 – of her own multiyear R01 grant from the National Institute of Allergy and Infectious Diseases of the NIH being used to explore the link between food allergies and neurodegeneration. The latter project looks to determine the role of immune cells in allergy-associated changes in the brain.

• Mikhail Golovko, associate professor in the Department of Biomedical Sciences, also has been awarded an NIH R01 Supplement Grant in the amount of $323,800. This supplement will build on the award that Golovko’s group was given in 2021 to study a novel brain pro-growth mechanism activated under low-energy conditions. The project originally funded by the NIH’s National Institute of Neurological Disorders and Stroke and National Institute on Aging will address alterations in this mechanism in the aging brain and its contribution to age-related neurogenerative disorders such as Alzheimer’s disease and Parkinson’s.

• Finally, post-doctoral researcher in the Department of Biomedical Sciences, Yingying Liu, was selected by the department as the 2022 recipient of the Outstanding Postdoc Award. Dr. Liu’s impressive scholarly production has included publishing six papers with retiring SMHS professor Min Wu, most of which explore the interaction between bacteria and the bacteriophages that “eat” invasive bacteria, including a group of Toll/interleukin-1 receptor (TIR)-containing proteins and the thoeris system in bacteria.

“Our data unveiled that the TIR system armed the E. coli bacterium with ability to cope with phage infection, allowing for bacterial defense against invaders,” said Liu, whose first-author paper was published in Science Advances recently. This award is accompanied by a $1,000 travel award and a commemorative plaque that will be presented to Liu.

• And in case you missed it, late in 2022 the NIH awarded a $1.6 million R01 grant – the highest award researchers can receive from the NIH – to Catherine Brissette, associate professor in the Department of Biomedical Sciences, to continue her studies into Lyme disease.

This grant will allow Brissette’s team, including co-investigators and SMHS faculty David Bradley and Timothy Casselli, to study bacterial and host factors in the pathogenesis of Lyme-induced neuroborreliosis, a neurological condition caused by Lyme disease that can range from headaches and mild meningitis to more serious manifestations such as vasculitis. In Lyme disease, the bacterium Borrelia burgdorferi causes an infection with diverse clinical outcomes including a variety of neurological symptoms.

Accordingly, Brissette’s group is looking to directly assess bacterial and host factors leading to severe inflammatory CNS involvement, as well as test potential interventions.

Many such research projects are ongoing at the SMHS, which was awarded nearly $49 million in fiscal year 2022 for its research and service missions. This amount represented a single-year record in sponsored funding for the school.

Specifically, the SMHS won a total of 104 awards from external agencies such as the NIH, Centers for Disease Control & Prevention, National Science Foundation, the state of North Dakota and other entities and foundations totaling $48,651,717. This figure follows a several-year growth trend in external funding awards to the school; over the past decade, the school has brought in nearly $320 million in funding to UND for biomedical research and related purposes.

Editor’s note: The quote in the headline is from Zora Neale Hurston, an American author, anthropologist and filmmaker. The full quote is as follows:

“Research is formalized curiosity. It is poking and prying with a purpose. It is a seeking that he who wishes may know the cosmic secrets of the world and they that dwell therein.”