Saving Lives with Basic Science

A focus on ending deadly seizures.

Author | Margarita Bauzá

Photo courtesy of Lori Isom

Growing up the eldest of four in Oshkosh, Wisconsin, Lori Isom, Ph.D., worked in the office of her father, a surgeon. By observing procedures in the operating room and emergency department, she found her first love: science.

"I was able to watch surgeries and discuss pharmacology with anesthe­siologists," she says in the lab that bears her name at Michigan Medicine, where she is the Maurice H. Seevers Collegiate Professor of Pharmacology and chair of the department.

Today, Isom leads a team of re­searchers who work diligently to solve the puzzle behind Dravet syndrome, a deadly type of pediatric seizure disorder that carries a high risk of Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP affects one in 1,000 people with seizures. Isom's team has published over 90 studies and gar­nered more than $22 million in research and fellowship grants, including a Javits Award from the National Institute of Neurological Disorders and Stroke.

Her lab, which employs between 15 and 20 researchers at any given time, is producing potentially life-saving discoveries. Isom and U-M physician-scientist Jack Parent, M.D. — the William J. Herdman Professor of Neurology and co-director of the Comprehensive Epilepsy Center — recently discovered that children with Dravet syndrome can have substrates for cardiac arrhythmia in addition to seizures, which may put them at higher risk for SUDEP. This suggests that increased sodium current in heart cells may be a biomarker for SUDEP risk and that a simple cardiac evaluation in children with Dravet syndrome can identify potentially deadly arrhythmias. (Read about Isom and Parent's recent research findings.)

Isom, who is also a professor of neurology and of molecular and integrative physiology, was inspired to work toward a cure for SUDEP after meeting families who have lost chil­dren to it, or who live in fear that they might. "In patients who have thou­sands of seizures in their lives," Isom says, "we need to understand why they experience the one that kills, and what perfect alignment of the planets has to happen in their brains and hearts."

Isom's Path to U-M

After high school in Wisconsin, Isom enrolled at Washington University in St. Louis, where she discovered the vast world of scientific research. Soon she was elbow-deep in buckets of earthworms, from which she purified and studied tropomyosin (a protein involved in muscle contraction), and writing basic science papers in a biochemistry research laboratory.

In 1983, she enrolled at Vanderbilt University to pursue a Ph.D. in pharmacology and later became a post-doctoral fellow at the University of Washington. There, she began cloning and sequencing sodium channel genes long before the Human Genome Project was completed and celebrated worldwide in 2003.

She arrived at the University of Michigan in 1995 as assistant professor of pharmacology. She was drawn to U-M for its neuroscience program and world-class Transgenic Animal Model Core facility. Here, she would be able to flex her research muscles studying sodium channels, which play a critical role in neural and cardiac excitability and the occurrence of epilepsy and cardiac arrhythmias.

"We began by studying basic sodium channel biology and trying to understand structure-function relationships," she says of her research program when she arrived.

Big sequencing projects to shed light on genes linked to epilepsy were starting to happen. Soon enough it was discovered that sodium channel genes, the focus of her work, played a key role in epileptic encephalopathies. Because Isom's team had cloned those genes and generated mouse models, they were well poised to translate their work to human disease.

"There Are Patients Waiting"

A decade after arriving at U-M, Isom crossed paths with Parent, whose research focused on Dravet syndrome, work that unequivocally intersected with hers — and "that changed the world," she says.

"My basic science research program went from 'knowledge for knowledge's sake,' to 'there are patients waiting,'" she says. "There was an urgency that wasn't there before. It was life and death work for children with a devastating disease."

Despite her lab's discoveries, everyone's biology varies, so what works for one patient may not work on another. The work is grueling and slow. It takes years.

"We'd like to make ourselves not needed," she says of her ultimate career goal. "We'd like to cure this disease. What these kids go through is overwhelming; many will not make it past adolescence. If we could stop this, it would be a great relief, not just for the kids but for their parents. I have had parents tell me that their biggest fear is that they will outlive their child with Dravet," Isom says.

"Parents know a lot about the science because their child's life depends on it," Isom adds. "They read everything, they ask great questions, and they often play a role in helping to fund our research."

Isom loves that her career merges her desire to help these families with her love of "understanding things, solving puzzles, finding answers. What you do when you lose all track of time — that's where your heart is. To me, science is not work. All translational research comes from basic science. But when you add a human element, that's when you know your work really matters."

A Role Model to Women Scientists

Isom is rare not only in her groundbreaking work but also because she is one of very few women at the highest levels of the scientific community, something she is determined to change.

"We are often our own worst enemies," she says. "We don't think we are good enough. We really suffer from impostor syndrome."

The glass ceiling, she says, "is often the biological clock. The time in our careers when we are the most productive often coincides when we begin having children." She realizes she is a role model for other women because she is a mother and has achieved groundbreaking science. "What many fail to realize is that I started having children when I was a postdoctoral fellow. And I made it," she says. "My daughter likes to say, 'My mom is chair of pharmacology, and I'm still alive.' You have to let other women know your story so they know it can be done and that you understand what it's like to go through this."

When asked who inspires her professionally, she identifies another woman scientist: Sally Camper, Ph.D., the Margery Shaw Distinguished University Professor of Human Genetics and former chair of the department. "She was the first female basic science chair at the University of Michigan Medical School and is a true role model," Isom says. "She conducts a world-class research program and is a fabulous administrator, but even more importantly, she cares deeply for every person she mentors.

"Once, in a group, we were all asked what we were most proud of. While everyone spoke about papers they had published, Sally, who was probably more famous than anyone in the room, said she was most proud of the people she trained and the people whose lives she was able to change. To me, the human element, the lives we change, is really what matters."

More Articles About: pharmacology seizures Dravet syndrome epilepsy Neurology molecular and integrative physiology SUDEP
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