The Science of Healing
By Johanna Musgrave
June 6, 2023
Brendan Williams ’20 has always been drawn to life’s deep and complex questions, so his choice to pursue a doctorate in systems and cellular neuroscience at the University of Texas at Dallas seems perfectly fitting. However, for Williams, studying neuroscience was a pivot in his original plans.
“When I first got to JBU, I had already mapped out how to be fluent in French and graduate with an international business degree and MBA in three years. My advisors were shocked,” Williams said, laughing.
But during his first semester, Williams developed a keen interest and empathy for people struggling with substance abuse and changed his major to family and human services.
It wasn’t until he studied neural circuitry of mood disorders in a lab led by Assistant Professor of Biology Qian (Angie) Wang, Ph.D., that Williams felt anchored.
“I suddenly saw this way of assessing the questions I had. It was really exciting,” Williams said.
Wang’s lab fueled his enthusiasm for neuroscience and became a critical launching pad for Williams’ current position. Under Wang’s supervision, Williams learned to present research, study animal behavior and slice and image the brain, among many other skills.
Williams joined the lab of Crystal Engineer, Ph.D., at UT Dallas in January 2022 to study the speech processing impairments seen in neurodevelopmental disorders, like autism spectrum disorder (ASD), in an effort to improve the efficacy of current therapies.
“For individuals with ASD, these impairments in processing speech sounds may be a function of developmentally altered brain structures,” Williams said. “When neural sound processing is even slightly altered, it can result in large cascading deficits in the brain’s ability to locate the source of a sound, to recognize a group of sounds as a word or to understand the semantics of a language.”
Alongside a team of researchers, Williams is working to reverse the neural deficits responsible for disordered auditory processing in a rodent model of ASD by exploring the use of sound-paired vagus nerve stimulation as a potential adjunctive therapy.
The end goal of the research is to improve therapeutic outcomes for individuals with ASD. Currently, the most widespread interventions are time-consuming, expensive and yield only modest improvements.
“I was drawn to the research because of the mechanistic training it would provide me and the potential impact of our discoveries on the lives of people with ASD and their caregivers. It’s important work,” Williams said.
Upon completing his doctorate, Williams plans to remain in academia, studying emerging therapeutic techniques at the intersection of neurobiology and psychology.
“Our life experiences influence our perceptions of reality, our psychology and our physiology. Neuroscience can teach us how, and even why, that happens.” Williams said. “Ultimately, I want to make discoveries that empower people to heal and thrive.”
Similarly, Olivia Lawler ’21, a predoctoral researcher at The Stowers Institute for Medical Research in Kansas City, Missouri, hopes to use her doctorate in biology to find a cure for Parkinson’s disease.
“My dad was diagnosed with early-onset Parkinson’s disease when I was two. I never knew life with my dad before Parkinson’s,” Lawler said.
However, Lawler didn’t always aspire to be a scientist. She assumed she would be an English teacher until she saw a centrifuge machine in ninth grade.
“I was inspired. I went home and thought, ‘I think this is something I could do. And, I might as well find the cure for Parkinson’s disease while I’m at it,’” Lawler said.
But until she completes her doctorate and starts her own lab, Lawler is studying the functions of proteins in long-term memory formation, specifically a protein named CPEB2.
“When people make memories, specific circuits in our brain are activated, and those connections need to remain strong to maintain those memories,” Lawler said. “In invertebrates, like fruit flies and snails, CPEB proteins form amyloid structures to maintain the memory connection over time. I’m exploring if CPEB2 functions the same in vertebrates – like mice and humans.”
To answer this question, Lawler trains mice under an “inhibitory avoidance paradigm.” In the experiment, Lawler places a naive mouse in an enclosed chamber that is well-lit on one side and dark on the other. When the mouse – naturally light-averse – runs to the dark side of the chamber, Lawler initiates an electric foot shock and removes the mouse from the chamber. Lawler waits 48 hours to consolidate the memory of the foot shock and then retests the mouse.
“After 48 hours, I measure how much time it takes the mice to cross into the darkness – sometimes, even after 20 minutes, they stay in the light,” Lawler said. “While they are obviously agitated and stressed, the mice will behave this way even several weeks after the initial training, indicating that the memory remains strong enough to override their natural instincts.”
But to thoroughly evaluate the role of CPEB2, Lawler is in the process of snipping the CPEB2 gene out of the mice already trained in the paradigm. She hypothesizes that if CPEB2 is important for maintaining strong memories in vertebrates, then reducing the genetic expression of CPEB2 in the trained mice will weaken or eradicate the memory altogether.
While results are forthcoming, Lawler’s work to define the specific role of CPEB2 in memory formation could change how researchers view and interact with amyloid structures, which are currently considered toxic to the human brain.
“This study could be the first evidence for a vertebrate brain amyloid that has a helpful, nontoxic function,” Lawler said. “I think this is the most exciting aspect of my work.”
She credits her confidence in her postgraduate work to her training and experience at JBU. Like Williams, Lawler worked in Wang’s lab, where she first learned how to handle and dissect mice and write publication-style lab reports, skills she’s using daily in her current position at Stowers.
“My professors and coursework consistently challenged me beyond where I thought I could go,” Lawler said. “I’m so grateful I am learning to become the researcher I imagined I could be in ninth grade.”
