By Aleksandra Vujicic

Although brain research has seen many major advancements over the past few decades, neuroscientists still face a huge limitation in not having access to human brain tissue for molecular and genetic research. 

Until recently, researchers had to rely on post-mortem brains or animal models to study brain development and what may go awry in psychiatric disease. Although investigating mouse and rat brains has led to major psychiatric discoveries, there’s still quite a translational gap when comparing these alternative models to a much more complex human brain.

Aislinn Williams, MD, PhD, assistant professor of psychiatry, who recently joined the Department of Psychiatry and the Iowa Neuroscience Institute, is working to bridge that gap by using stem cells to create neurons, an approach that has emerged in many modern-day research institutes and is becoming more prominently cited in major research journals.

The process involves taking human skin samples and reprograming skin cells to become brain cells, and sometimes even bits of brain tissue.  

Williams, who received her MD, PhD training at the University of Iowa and went on to complete her psychiatry residency at the University of Michigan, is looking into gene expression patterns that may play an important role for brain development and how normal development may be altered in patients with schizophrenia and bipolar disorder. Her work with stem cells aims to identify the pathways that are important for disease risk, which may ultimately lead to better-targeted treatments.

Williams starts with taking a small skin sample and purifying fibroblasts found underneath the top layer of skin. The cells will keep their DNA structure, but through this two-week process they will lose their connective tissue cell properties and resemble embryonic cells.  Those stem cells can then be used to make neurons.

“At this point, they really are the best system we have for trying to obtain neural tissues from people that we can still talk to,” she said. “We can study what genes are important for brain development.”

Since the new neurons are not derived from embryos but from human subjects, it offers researchers the unique ability to ask questions about symptoms, medications, and other unique features of each patient.

“I’m trying to help bridge the gap between what we know about genetics and what we know about disease,” Williams said. “I think it will help us understand the brain in general and hopefully identify new ways to intervene for people where other interventions haven’t been so helpful.”

The approach offers an exciting, new opportunity to study the human brain, but it’s also a system that is changing and growing rapidly. Researchers aren’t quite able to create a whole human brain from stem cells but some labs have been able to develop what’s known as cerebral organoids, or a cluster of stem cells that generate brain-like tissue. Over time, the, clusters of living brain cells start to develop layers of the cortex like what is seen during embryonic development.

“I would’ve thought this was complete science fiction, but it’s something that stem cells have shown us is possible,” Williams said. “We aren’t making brains but we are looking at the early embryonic and fetal processes that contribute to brain development.”

Williams, who has already set up a lab to continue both her animal and stem cell work, chose to join the INI because of the resources and mentorship it provides. She was impressed by the imaging and animal facilities within steps of one other and an impressive set of mentors that are nationally and internationally renowned, including Ted Abel, PhD, Director of the INI.

“That’s really what pulled me in, knowing that the department knew how to build successful research programs,” she said. “They do it all the time, and they’ve been doing it for many years. And then you add on with the collaborative synergy between the department and the INI…that kind of energy is pretty rare.”