In his lab in the Hamon Biomedical Research Building, Dr. Lu Sun, Assistant Professor of Molecular Biology, studies glial cells to understand cellular mechanisms that underlie autism spectrum disorder (ASD) and other social behavioral abnormalities. Four floors down in the Takahashi lab, Research Scientist Dr. Chang Hoon Lee is searching for new molecular targets to alleviate mental impairments – such as sleep disruption and memory deficits – associated with ASD. Both recently received Young Investigator Grants from the Brain & Behavior Research Foundation.

Since 1987, the Foundation has awarded over $418 million in research grants to more than 6,000 scientists globally, supporting early career investigators in groundbreaking neurobiological research to identify causes, improve treatments, and develop prevention strategies for psychiatric disorders. In 2020, the Foundation’s Scientific Council selected 150 Young Investigators from 1,012 applications. Each scientist will receive up to $35,000 per year for two years.

Dr. Sun hopes to better understand the roles of glial cells in neurological disorders including autism – a largely overlooked area of research, he said. “This grant gives us an opportunity to test several bold hypotheses, some of which could possibly open up new research directions.”

Dr. Sun will focus on oligodendrocytes, a specialized glial cell that generates a protective structure around the nerve fibers to allow for proper nerve signal transduction. His team will characterize oligodendrocytes and myelination – the process of wrapping around nerve fibers – in several autism mouse models to determine if the location and timing of myelination are disrupted. Based on this information, the researchers will use genetic and pharmacological approaches in these animal models to manipulate myelination in order to possibly reverse autism symptoms.

“This work will determine some fundamental cellular mechanisms underlying autism from a completely different perspective,” said Dr. Sun, who joined UTSW last year after completing postdoctoral training in glial biology at Stanford University and earning his Ph.D. in neural circuitry assembly at Johns Hopkins University. “We hope that our basic research will provide novel ideas in rethinking these neurological disorders. As previous work is primarily focused on how dysfunction of neurons causes neurological disorders, we are trying to bring a broader view regarding how neuron-glial interactions shape the brain in health and sickness.”

Dr. Lee’s ultimate goal is to unravel how ASD disrupts brain activity to cause mental health impairments such as sleep disruption and memory deficits, as well as reveal connections with other neuropsychiatric diseases – such as intellectual disability, depression, and schizophrenia.

“Through this work, I will discover new molecular targets to alleviate these impairments in ASD,” he said. “This award will be integral to the completion of experiments needed for transition to independence and secure further funding.”

Dr. Lee will use genome-wide neuroinformatic approaches to shed light on mechanisms driving sleep disturbance in ASD. Building on his prior work, he hopes to demonstrate that short noncoding RNAs – orphan C/D box small nucleolar RNAs – carrying ASD-risk aberrant alternative splicing activities underlie sleep disorder in ASD and are possible novel therapeutic targets.

“About 80 percent of ASD patients experience chronic sleep disorder and fatigue. However, the mechanisms underlying these problems are largely unknown,” said Dr. Lee, who came to UTSW in 2017 after completing postdoctoral training at UCLA studying ASD and earning his Ph.D. at the Institute for Cell and Molecular Biology at UT Austin. “Sleep is critical to mental health, and chronic sleep disruption is strongly associated with depression and anxiety disorders, in addition to memory and cognitive impairments. By uncovering mechanisms of sleep disruption in ASD, we can identify possible therapeutic targets to improve sleep and a variety of other disorders of mental health.”