New lab explores the genetic and environmental factors related to psychiatric conditions such as schizophrenia and autism

In 2003, the Human Genome Project generated the first sequence of the human genome, and the years that followed accelerated the study of human biology and advanced the practice of medicine. The genetics of psychiatric conditions are proving particularly difficult to unravel, but there have been major advances in the last decade.

“It has been an exciting time, a new era of genetics and genomics,” said Ryan Purcell, the newest assistant professor to set up a lab in the Center for Neurobiology Research at the Fralin Biomedical Research Institute at VTC. “We've known for many decades that serious psychiatric conditions have a strong genetic component, but it wasn't clear which genes were involved.”

Purcell, who also holds an appointment as an assistant professor of neuroscience in Virginia Tech’s College of Science, investigates genetic variants and environmental factors that increase the risk for certain psychiatric conditions in the developing brain.

“There was this thought that, really soon, we were going to know which genes are involved in some of these diseases, like schizophrenia,” he said. “But it turned out that it was a much more difficult problem.”

He sees it as a puzzle.

“Advances in genetics have identified a lot of the puzzle pieces, but right now in 2024, you can’t get a molecular test from a doctor that will indicate you have a psychiatric condition. That's how far behind we are to other areas of medicine,” Purcell said. “My job is trying to understand how these genetic puzzle pieces fit together, and how they may alter brain development.”

Purcell’s original plan was to become a physician, but he wanted a break between his undergraduate studies in neuroscience and medical school. A few years as a research technologist at Johns Hopkins University seemed a perfect way station. Instead, he changed course.

“I just fell in love with research,” Purcell said. “I loved the idea of working on new problems and trying to advance knowledge in ways that have not been done before.”

He went on to earn his doctoral degree at Emory University and conducted postdoctoral research there as well. As a postdoc, he studied a chromosomal variant called the 3q29 deletion, which is a strong risk factor for schizophrenia. These studies involved a mouse model of the disorder and induced pluripotent stem cells, or iPSCs, which have transformed in vitro research by allowing scientists to study previously inaccessible cell types, like neurons, which carry disease-associated genetic variants of interest.

Purcell was aware of the work of Anthony LaMantia, a professor at the Fralin Biomedical Research Institute and head of its Center for Neurobiology Research. For more than two decades LaMantia has investigated DiGeorge syndrome, also called 22q11.2 deletion syndrome, a disorder that that occurs when a small part of chromosome 22 is missing. The disease’s effects include cardiovascular problems, craniofacial developmental issues, autism spectrum disorder, and schizophrenia.

After being promoted to a research assistant professor position at Emory, Purcell investigated mechanisms and genes associated with 3q29 and 22q11 deletion models, work he plans to continue with Virginia Tech.

“It turns out that this specific genetic variant, 3q29 deletion, seems to do some similar things as another variant called 22q11, which is what the LaMantia lab studies,” Purcell said. “We think some of these high-risk genetic variants might be disrupting similar biology in different ways.”

While at Emory University, Purcell also overlapped with Assistant Professor Sharon Swanger, who now has her own lab at the Fralin Biomedical Research Institute, where she studies the synaptic signals and disruptions that can lead to epilepsy, psychiatric diseases, or movement disorders.

“There's a lot of opportunity to collaborate with people here,” Purcell said. “My impression so far has been that everyone at FBRI is just very invested, and wants to do whatever they can to help everyone else succeed. It feels very welcoming and exciting.”

That spirit extends beyond neuroscience.

Purcell looks forward to broad collaborations, not only within neuroscience but with exercise and cardiovascular researchers, since genetic syndromes are systemic, whole-body conditions.

While the chance to be part of an innovative biomedical enterprise drew him to Roanoke, there was another plus: its outdoor culture. Purcell, who lives near the Roanoke River Greenway, is an avid runner and plans to explore the region’s wide network of trails.

He served as a guide during the 2013 Paralympics Track and Field World Championships in Lyon, France, for Ivonne Mosquera-Schmidt. The professional athlete and entrepreneur, who lost her sight to retinal cancer when she was 2 years old, placed sixth and ran a personal best in the 800-meter run.

“Ryan’s superb work embodies the sort of intellectual fearlessness and commitment to new technologies necessary to take on one of the most difficult problems in neuroscience — how complex genetic changes map on to life-changing brain diseases like schizophrenia,” said LaMantia, who is also a professor of biological sciences in the College of Science. “I have no doubt that Ryan will provide for his colleagues here at the institute, Virginia Tech, and beyond, new fundamental and translational insights at the interface of genetics, neurobiology, and human behavioral/brain disorders.”

Michael Friedlander, executive director of the Fralin Biomedical Research Institute and Virginia Tech’s vice president of health sciences and technology, seconded the impact of his work. “Ryan has chosen to take on a set of the most challenging and potentially life-altering problems in all medicine – the biological basis of profound neuropsychiatric disease. The promise of his work to help millions of people is enormous, but it is one that has stymied many brilliant and hard-working scientists.  Ryan is armed with the tools, the intellect and the commitment to tackle this challenge.  I am confident that his work will at a minimum provide impactful new insights into these disorders – and perhaps, a real breakthrough. We are delighted to have him join the institute and we look forward to his success.”

Purcell’s research is funded by the National Institute of Mental Health, part of the National Institutes of Health.