Dr. Sami Barmada: Understanding the long-term impact of concussion through a molecular lens

Situated on the corner of Glen Avenue and East Huron Street in Ann Arbor is the Biomedical Science Research Building, sometimes nicknamed “the Pringle,” which is home to nearly 240 state-of-the-art research facilities, including Dr. Sami Barmada’s lab.

Sami Barmada is the Angela Dobson Welch and Lyndon Welch Research Professor and an associate professor in the Department of Neurology. He also oversees the University of Michigan’s Brain Bank. Overlooking the university’s medical campus from his fourth-floor office, Barmada actively engages in neurodegenerative disease research focused on a nervous system disease called Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD). 

Abnormal protein deposits and accumulations in our brains could cause diseases like Alzheimer’s and chronic traumatic encephalopathy (CTE). One of the proteins that Barmada is studying is TDP43, an essential element responsible for different aspects of RNA processing, including splicing, translation, and transport. When the TDP43 protein is not located correctly in the brain, the cells will not be able to survive due to interrupted RNA processing, which then causes neurodegenerative diseases such as ALS and FTD.   

In addition to age-related degenerations, TDP43 also builds up in patients who sustained numerous mild traumatic brain injuries (concussions) and have developed dementia later in life. “There’s a strong connection between TDP43, FTD, and the condition we now call CTE due to repetitive head injuries,” said Barmada. “Why does this happen to TDP43? What does this have to do with the development of symptoms, and what can we do to stop it?”

For Barmada, seeing the changes at the molecular level for age-related neurodegenerative diseases, such as ALS and FTD, has allowed him to understand these conditions further. Additionally, examining the functions of TDP43 might shed some light on what happens in concussion-related injuries when this protein is “not in the right place,” Barmada said. It could also reveal other potential concussion biomarkers and lead to understanding the mechanisms of disease that potentially cause CTE. Together with collaborators at the University of Michigan, he is currently looking at different proteins and RNA molecules that can show changes in TDP43 function or localization in patients before symptoms develop. Consistent with the Concussion Center’s research mission to understand and promote long-term brain health, Barmada notes critical findings that could be equally influential for concussion treatment and long-term management.

A challenge for Barmada is figuring out who is most at risk for developing neurodegenerative problems later in life.

“Somebody has a concussion, and then 20 years later, they develop dementia. What happened during those 20 years?” asked Barmada. “Having some measure or biomarker that we could detect would give us a leg up on not just identifying who’s at risk, but acting early enough to reverse it,” he added.

As director of the Michigan Brain Bank, Barmada sees many opportunities to work with the U-M Concussion Center on concussion-related research.

“We want to look at the similarities between age-related neurodegenerative disorders on the one hand and concussion/CTE on the other. We also want to provide resources to other investigators who want to study the same problem,” he said.

The U-M Biosciences Initiative recognized Barmada’s work by selecting him as one of the Mid-career Biosciences Faculty Achievement Recognition (MbioFAR) Award recipients. The MbioFAR, established in 2021, recognizes exceptional mid-career faculty in sciences and provides discretionary funds to encourage innovative, high-risk research.

He was one of six U-M research scientists to receive the award.

While Barmada’s lab has previously built prospective imaging systems for brain cells and neurons, there have been limitations in what they can measure due to technical difficulties such as low microscope resolution. He is excited about the possibility of conducting more robust assessments with the Biosciences Initiative’s support.

“Their support feeds right into what we’re doing. It opens doors,” he said. “There are many exciting, risky things we’ve wanted to do for years but haven’t had the chance. This is our chance.”