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Undergraduate researchers at Creighton target multiple sclerosis

Nov 2, 2022
3 min Read
Eugene Curtin
Annemarie Shibata, PhD, poses in her research lab
Annemarie Shibata, PhD, professor of biology, will lead a group of 12 undergraduate students in research funded by an NIH grant.

Twelve Creighton University undergraduates will have the opportunity during the next three years to strike a blow against one of humanity’s most devastating diseases. 

With the support of a federal grant, the students will research the relationship between systemic inflammation and the subsequent onset of neurodegenerative diseases such as multiple sclerosis.

The research will engage four undergraduate students in each of the three years of the study, for a total of 12 students. Nine of these will be funded directly by the NIH grant with the remaining three funded by the University, which will direct grant funds for indirect expenses to sponsoring the students. 

“The students will participate in all of the experimentation once the animals are infected with the virus,” Shibata says. “They will be involved in experiments such as immunocytochemistry, the analysis of the brain structure, and in-situ hybridization, which is looking at where those long non-coding RNAs are expressed, and which cells are expressing them.” 

Their findings could also build understanding of the progression of other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease following inflammatory responses. 

Led by Annemarie Shibata, PhD, professor of biology, with the collaboration of Kristen Drescher, PhD, professor of medical microbiology and immunology, the study aims to shine light on why viral inflammation is associated with neurodegeneration and progressive multiple sclerosis. 

The search for answers to that question is pressing, Shibata says. Epstein-Barr virus, for example, one of the most common human viruses, has been directly linked to an increased risk for developing multiple sclerosis.  It is, therefore, necessary to better understand the mechanisms that regulate viral inflammatory responses with the goal of identifying potential novel therapeutics.  

The study, which is titled “Regulation of the Microglial Neuroimmune Response by Long Non-Coding RNAs,” is funded by a three-year, $436,468, NIH Research Enhancement Award grant from the National Institutes of Health. Such grants are designed to support meritorious research while introducing undergraduate students to the principles and procedures of research. 

Since women tend to develop multiple sclerosis at greater rates than men, thereby suggesting the possible role of sex differences, the study will involve injecting a virus into the brains of male and female mice and then analyzing brain biochemistry and structure. 

The study’s central focus, Shibata says, is the behavior of “long non-coding RNAs.” These strands of RNA are known to react when inflammation is triggered in brain immune cells and might play a role in either controlling inflammatory responses and thereby preventing neurons from dying or contributing to dysregulated inflammatory responses that cause neurons to die.  

“One species of mouse will resolve and recover from the viral infection and the other will develop neurodegenerative disease,” Shibata says. “The role of long non-coding RNAs is of interest because we have found in other work a handful of long non-coding RNAs whose expression increases when we cause inflammation. They are potential targets for future therapeutic intervention. 

“There are two questions to address,” Shibata says. “First, what is happening in the inflammatory response of immune cells in the brain to viral infection during the development of progressive or chronic multiple sclerosis versus the inflammatory response during acute forms of MS that are not progressive?  

“Second, we would like to investigate what accounts for the differences between the sexes and why the disease progresses in women more than it progresses in men.” 

Among the important contributors to the preliminary study data, Shibata says, is former Creighton professor of medical microbiology and immunology Xian-Ming Chen, MD; Nicholas Mathy, MD, PhD, Olivia Burleigh, BS, and Aaron Marta, BS, recent Creighton graduates; and undergraduate students Sophie Ciechanowski, Emily Daffer and Collin Jackson.