91AV’s Russ Ferland receives $568,000 NIH grant to further epilepsy research
Russ Ferland planned on becoming a lawyer when he was an undergraduate student at Providence College, until two biopsychology professors introduced him to neuroscience and invited him to help in their research, an experience that changed Ferland’s life forever.
It’s one of the reasons Ferland went into teaching and research, and why, after 30 years of researching neurological diseases and disorders of brain development, Ferland took a job as a professor and chair of the Department of Biomedical Sciences at the 91AV in 2019. He wanted to pay it forward and inspire more students to take part in neuroscience research.
“I feel profoundly fortunate and grateful for that experience that determined my fate. And I always said to myself, ‘Wouldn't it be great to work at institutions where I could hopefully have that effect on at least one person?’” said Ferland, who also teaches medical students in Maine’s only medical school, 91AV’s College of Osteopathic Medicine.
Now, Ferland will return to research that was the focus of his scholarship before coming to 91AV: the study of epilepsy and sudden unexpected death in epilepsy, (SUDEP). After receiving a National Institute of Health biomedical grant for $568,000 this summer, Ferland will conduct research on mechanisms of how epilepsy develops and why SUDEP can occur.
This fall he plans to recruit 91AV medical students and a few undergraduate research assistants to help in the four-year study that will examine how seizures change over time, leading to increased risk for SUDEP.
Specifically, Ferland wants to look at the ventromedial nucleus of the hypothalamus (VMH) to understand its role in epilepsy progression and its potential involvement in SUDEP.
“Scientists are looking at mechanisms of SUDEP in the brainstem, specifically those brain centers that you don't want to have abnormal seizure discharge propagating through, like the respiratory centers and the cardiac centers. But how that seizure discharge gets to these areas to cause a problem is unknown, but maybe it’s through the VMH. So, we need to look there as that is where our data are pointing us,” said Ferland, who has studied epilepsy since 1994.
“This research is going to address this question using multiple tools. There’s going to be genomics in this project. There’s going to be a lot of bioinformatic and genomic data produced in this study that needs to be analyzed. So, there’s really all kinds of projects that could appeal to students.”
Before coming to 91AV, Ferland was working on this line of inquiry at Albany Medical College, where he was a professor and served as vice chair of the Department of Neuroscience and Experimental Therapeutics. In past work, Ferland identified how, during seizures, the VMH seems to serve as a kind of gateway to the brainstem, propagating the kind of tonic seizures that can increase risk for SUDEP.
In studies using animal models, Ferland found that after eight induced seizures, the VMH undergoes a reorganization process, during a 28-day pause when no seizures are induced, that allows a new induced seizure to propagate from the forebrain seizures system to the brainstem seizure system, resulting in tonic seizures that can increase risk for SUDEP. That reorganization, Ferland said, may be a key to helping to prevent SUDEP.
Preliminary data that Ferland hasn’t published suggests that deleting one gene in the VMH could prevent this brainstem seizure. The grant will fund the continuation of that work.
“Could it be due to gene expression changes that are somehow altering cells within the VMH so that we get these brainstem seizures?” Ferland posed. “We think this could be a good model for not only understanding how seizures change over time, but we think it could be important for understanding more about SUDEP.”
Using a relatively new technology called spatial transcriptomics, Ferland will be able to better study signaling pathways in specific cells within the VMH that may be involved in tonic seizure expression and increase risk for SUDEP.
“The hope is that a gene pathway changes in the VMH that could be responsible for the increased SUDEP risk and may serve as a druggable target. It’s always hit or miss when you’re doing this discovery work in science,” Ferland said.
Ferland has published more than 60 peer-review articles on neurological brain conditions. Still, he likes to say science is serendipitous, because sometimes it’s only luck that leads a dogged investigation to a breakthrough.
Then again, serendipity led to the detour in Ferland’s career when he took a class in neuroscience on a whim his junior year of college.