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NIH grant supports continued studies on how to target cilia for therapeutics

Dr. Wissam AbouAlaiwi and the pharmacy students in his lab continue to earn accolades for their research on cilia, the tiny hair-like structures that emanate from the surface of cells in our bodies and act as sensory antennas.

The University of Toledo assistant professor secured in January a highly competitive $400,000 National Institutes of Health grant, the fourth award his lab has earned since it opened in 2014, to further his cilia research. But the award’s true objective, he said, is to groom future researchers.

AbouAlaiwi

“We want to stimulate students’ interest in research, so they stay in the biomedical research field and become research scientists,” AbouAlaiwi said.

His students already are receiving attention for their research, which was published in the October issue of the online Nature journal Scientific Reports.

AbouAlaiwi and his students’ research in the UT Department of Pharmacology and Experimental Therapeutics focuses on cilia. The motile type of cilia is important because they help move fluids throughout the body and nourish brain cells. Non-motile cilia function as sensors, triggering biochemical processes within the body.

The team of students that recently published their work studied how alcohol affects the function of cilia in the brain. The paper’s lead author was Alzahra J. Al Omran, a graduate student in pharmacology and toxicology track. She will be continuing her studies as a PhD student in the fall, studying pharmacology and experimental therapeutics in AbouAlaiwi’s laboratory. The team also included graduate students Hannah C. Saternos, Alexander Wisner and Yusuff Althobaiti.

Their research explored whether cilia in brain cells play a part in some of the first symptoms — headaches and confusion — experienced by someone who abuses alcohol.

Scientists already knew that malfunctioning cilia play a part in many genetic diseases. For instance, if cilia in the brain don’t do their job — to help circulate cerebral spinal fluid — fluid can build up in the brain in a condition known as hydrocephalus.

The UT team wondered whether malfunctioning cilia have anything to do with the symptoms of alcohol abuse. To figure this out, they needed to study the beating frequency of the cilia.

It was their method in doing this, as much as their results, that attracted the journal’s attention, AbouAlaiwi said.

In the past, scientists were not able to determine the exact effect on the beating frequency of cilia because they were looking at the organelles in cells, not in live animals.

UT researchers were able to see the cilia in action. They served up alcohol to rats and within a half hour, isolated their brains using a technique developed in their lab. They examined cilia while they were still beating in the brain and ascertained how frequently they beat.

The results didn’t surprise researchers: Alcohol significantly slows down the cilia and hampers its ability to mobilize fluids. This dysfunction could affect brain cell function and may contribute to headaches and confusion that accompany alcohol abuse.

In another first, the UT team discovered three kinds of cilia in brain ventricles. Each has a unique beating frequency and angle. Each also tends to congregate in a certain part of the brain ventricle — one kind at the ends and two others along the edges.

AbouAlaiwi said the research is still in its early stages. More research is needed on the characteristics of each kind of cilia and why they are distributed the way they are. But the more they can unearth about the cilia’s behavior in the future, the greater chance of developing drugs to repair the malfunctioning cilia and restore their beating frequency.

“We’re starting to explore cilia-based therapy,” AbouAlaiwi said. “If we can find drugs to specifically target cilia, we could one day find cures for these genetic diseases.”

The NIH grant also will support AbouAlaiwi’s ongoing research suggesting that the cardiovascular symptoms of patients with polycystic kidney disease may be caused by malfunctioning or mutated cilia.

AbouAlaiwi, in research that hasn’t been published yet, discovered a family of receptors found in primary cilia, the kind of cilia that act as sensors to transform signals into active biochemical processes in the body. It was the first proof scientists had that cilia house this family of receptors.

Receptors have been the primary focus of research on neurodegenerative disease, AbouAlaiwi said. He’s now studying whether the receptors have anything to do with polycystic kidney disease and hypertension.