Faculty Spotlight: Fueling Neurons

Using microscopic worms as a genetic model for gene discovery, Osama Refai, Ph.D., discovered a gene in the brain energy supply that could bring him one step closer to aiding symptoms of Parkinson's disease.

Death of dopamine neurons in the brain is a major hallmark of Parkinson’s disease, said Refai, who is a research assistant professor in the Charles E. Schmidt College of Medicine and a faculty member in FAU’s Stiles-Nicholson Brain Institute.

“Decreased levels of dopamine due to damaged dopamine neurons leave Parkinson’s patients to suffer from tremors, movement slowness and balance problems,” Refai said. “But using the worm-like creatures known as C. elegans, I’ve discovered a gene that can recharge the dopamine neurons, regulate the dopamine levels in the brain and minimize those symptoms.”

The new gene is expressed in the mitochondria of the dopamine neuron. Mitochondrial are important cellular organelles that are known to be the powerhouse of the cell. Failure of mitochondria to provide sufficient energy to the cell leads to cellular death, as in Parkinson’s disease.

Our brain is energy hungry organelle and neuronal cells are high energy demanding cells, thus they are vulnerable to changes in mitochondria. In fact, when the new gene is mutated in the C. elegans worms, they show signs of dopamine neurodegeneration, a major sign of Parkinson’s disease, Refai said.

Therefore, Refai said he thought to promote energy production in dopamine neurons of Parkinson’s patients to protect these neurons against factors of cell death.

Working at the Blakely laboratory at FAU, Refai used a worm-model for Parkinson’s disease that mimics death of dopamine neurons in the brain of Parkinson’s patients. Once the worms begin showing signs of the disease, he then delivers a healthy version of the mitochondrial gene into the worms until the symptoms decrease, he said.

With an interest in human health and diversity, Refai earned a master’s degree in physical anthropology from Cairo University in Egypt.

This work allowed Refai to uncover the deeply rooted basis of inequality based on sex, race and socioeconomic status in the ancient Egyptian populations, he said.

“I found that females and the Egyptian workers from lower socioeconomic classes suffered more from deteriorating health and work conditions during the time of Giza pyramid building,” Refai said. And, it was there, he said, where he grew even more fascinated about studying the genetic bases of diseases to help disadvantaged groups.

Shortly after, Refai went back to school to earn another master’s degree in biology and human genetics from New York University in New York City.

In New York, he worked on a case of a baby born with a rare genetic disease of sexual determination disorder, he said. This project involved looking into genes necessary for sexual human development, such as what gene causes female babies to be born with male reproductive parts.

“I learned a ton about how our genes affect who we are as people, but I also realized that if I wanted to study more genetic mutations like the one in that baby, I couldn’t wait for it to happen naturally, rather I have to be able to generate these mutations” he said. Therefore, Refai decided to adopt the microscopic worm C. elegans as a model amenable for genetic manipulations.

It was during his doctorate program at the University of Calgary, Canada, when Refai said was first introduced to the relatively new genetic model C. elegans. There, he was able to perform a large-scale gene discovery experiment that involves generating thousands of novel genetic mutations.

This technique, he said, was instrumental in identifying a group of genes necessary for neuronal development and communication in embryos. After graduating, he completed a postdoctoral fellowship at Vanderbilt University in Tennessee, studying neurotransmitters in the brain such as dopamine and acetylcholine.

Refai joined FAU in 2016 to continue his work on dopamine and associated brain disorders such as Parkinson’s, attention deficit hyperactivity disorder and addiction. Recently, he published a paper in the journal of Molecular Pharmacology presenting C. elegans as a new tool for addiction studies focused on combating drugs of abuse such as cocaine and amphetamine.

“I’m hoping to use this method with the C. elegans to determine which drugs can dilute the effects of cocaine or any other amphetamine taken by addicts,” he said. “As with Parkinson’s disease, my goal is to get to a level where more genes can be found and we can ultimately prevent these diseases from happening.”