Central Michigan University (CMU) is putting its stamp on the world of research in higher education.

From studying effects of stress and aging on egg cells to finding cures for diseases and disorders, CMU’s resources and facilities are attracting bright minds in both students and faculty alike, and the work coming out of the university proves it.

“A lot of people think major medical research only happens in big medical centers like the one at U of M (University of Michigan),” Ari Harris, Assistant Director at CMU’s University Communications said. “But we have cutting-edge research aimed at improving global human health right here in Mt. Pleasant.”

Benjamin Swarts, Ph.D., Department of Chemistry and Biochemistry at Central Michigan University.

Tuberculosis: Persistent and resistant

Dr. Benjamin Swarts, an associate professor for the Department of Chemistry & Biochemistry at CMU, is one of those bright minds. Swarts and his team are using a novel approach to study Tuberculosis: synthetic chemistry.

Tuberculosis (TB) still resides among the World Health Association’s (WHO) list of the top 10 causes of death worldwide. According to the WHO, in 2017 10 million people were infected with TB, and 1.6 million of them died from the disease.

TB is caused by a bacterium called Mycobacterium tuberculosis, which typically affects the lungs, but can travel to other parts of the body through the blood. TB is spread from person to person when someone with an active TB infection disperses the bacteria into the air by coughing, sneezing, or speaking. Those in the vicinity can breathe in the bacteria and become infected. Not everyone infected with TB will show symptoms. Some while infected, may have what’s called latent TB. They are not ill, exhibit no symptoms, and are unable to transmit the disease, though it can become symptomatic later in life.

Swarts and his team are focusing their efforts on the outer membrane of the bacterial cell envelope, the layer which protects the bacterium during an infection. With better understanding of this membrane, such as its function and composition, Swarts hopes new strategies can be designed to improve TB detection or create treatment options that target the membrane itself.

Swarts says most forms of TB are treatable now, but that patients often do not complete their treatment, giving the bacterium the opportunity to mutate and return in a drug-resistant form. That’s because while treatable, TB is persistent and the course of treatment needed can be daunting. Treatment for a typical non-TB bacterial infection is usually one antibiotic, taken over the course of a few weeks at most. The standard treatment for TB, on the other hand, is usually three or four drugs to be taken in conjunction over a period of six months or longer. Finding a way through the cell membrane might help doctors treat patients more efficiently.

It was the opportunity to do research like this that attracted Swarts to CMU in the first place. Joining CMU in 2013, Swarts said he knew he wanted to work with undergraduate students in a research setting.

“I was surprised at how much investment was going on in research and the resources that are available here,” Swarts said. “It’s a pretty incredible facility and there’s a strong vision from the institution in terms of putting more emphasis on research.”

“Doing research on a disease that has a global reach, we are unique in that we are chemists and we’re developing new tools and compounds that other researchers around the world are interested in utilizing,” Swarts said. “That’s allowed my group to develop collaborations around the world which is beneficial to CMU and our community because it increases our research visibility. We’ve had students from other parts of the world who have taken notice of the work going on here and have come here to join our graduate programs.”

Mitochondrial Disorder: Understanding translating to treatment

Dr. Linlin Zhao, assistant professor in the Department of Chemistry & Biochemistry, is another bright mind that was attracted to the CMU team in 2013. Like Swarts, Zhao was looking for the opportunity to work alongside students in the lab, and the small town atmosphere of surrounding Mt. Pleasant sweetened the deal. “The town itself is a very affordable place to live,” says Zhao, “I have two kids and they can play safely. I don’t have to worry, unlike living in a big city.”

Zhao’s research focuses on mitochondrial DNA and the link to many diseases, cancers, and disorders when the DNA fails or is damaged.

According to the United Mitochondrial Disease Foundation (UMDF), mitochondria, commonly referred to as the powerhouse of the cell, are responsible for creating ninety percent of the energy needed for the human body to function. When mitochondria fail, various parts of the body are affected, but those requiring the most energy such as the heart or brain, are impacted most.

According to Zhao, there are about 200 known mitochondrial disorders.

“It’s actually being recognized as an important pathogenic source for a lot of other common diseases,” Zhao said. “There are solely mitochondrial disorders, but we also have common human disease, like cardiovascular disease and neurodegeneration, that link to mitochondrial dysfunction.”

Zhao and his team’s study focuses on analyzing how a small portion of mitochondrial DNA — about one percent, called encoded DNA, are damaged and subsequently repaired.

“Right now a lot of work is still on the test tube level, looking at cell lining,” Zhao said, “We’re hoping that by gaining understanding of the DNA repair process we could discover important molecules to be used to aid in the treatment process.”

Mitochondrial disease is difficult to diagnose because it affects individuals differently and can present through a wide variety of symptoms such as seizures, liver failure, or hearing loss.

Zhao said the average person with a mitochondrial disorder may see eight or more physicians before receiving an accurate diagnosis. “There’s such a wide spectrum of phenotypes and disorders that people could easily misdiagnose mitochondrial disease as something else,” Zhao said. The UDMF advises that when symptoms involve three or more organ systems, mitochondrial disease may be the reason.

Currently, treatment is focusing on increasing the energy production process. “If you have a dysfunction of mitochondria, you may have a lower energy level that will affect the tissue that those mitochondria are in,” Zhao said. “A lot of times patients will be given a nutrient supplement that will help to boost the energy level, to assist those dysfunctional mitochondria.”

If Zhao and his team can contribute a better understanding of the natural mitochondrial repair process, treatment in the future may be able to do more to repair dysfunctional mitochondria rather than just boosting lackluster energy levels. “With the emphasis the university has put on research, it’s an exciting time,” Zhao said, “We are going out into the scientific community and definitely putting our stamp on the world.”

Kevin Park, Ph.D., Assistant Professor of Psychology Neuroscience Program, works in the lab at Central Michigan University.

Alzheimer’s: More than bad memory

Dr. Kevin Park, psychology department faculty member and part of the neuroscience program at CMU, is yet another researcher currently working on cellular level dysfunction and repair. Park is studying Alzheimer’s, a progressive type of dementia that impacts memory and behavior.

The National Institute on Aging (NIA) describes neurons as specialized cells that are responsible for transmitting information throughout the human body. Alzheimer’s disease disrupts neuron communication, causing them to stop functioning and lose connection with other neurons. Without the ability to repair themselves the neurons ultimately die. This will manifest first in a person’s memory, then later affects areas tasked with reasoning or social behavior deteriorating until eventually the disease leads to the individual’s death.

“It’s a terrible disease,” Park said. “It robs a person of their personality- they become a shell essentially. It’s terrible to see people lose their ability of independence. Aging is the greatest risk factor. As you get older, your risk of developing increases. People didn’t live as long 100 years ago; you didn’t see it much. Now people are living longer, but at the same time there are environmental changes, more pollution, and lifestyle change and stress can lead to it also.”

As the disease progresses, two main proteins involved with the disease will cluster. Beta-amyloid form plaques between neurons and tau molecules form tangles inside neurons and block the system neurons use for communication.

Park and his team are using a mouse model study of Park’s own design to gain better understanding of the disease. The mice have been engineered to generate the plaques and tangles with their own proteins to imitate the gene mutation caused by Alzheimer’s disease.

“If you can generate plaques and tangles in these animals you’re now speculating that there might be a process to tap into to understand what might be generating that,” Park said. “It normally doesn’t generate those, so if it can formulate those pathological hallmarks and the key biological changes that are observed in humans, then the likelihood that that pathway is being modified in that system is what we are examining.”