Kepecs awarded NIH Director’s Pioneer Award
Grant will support research into how brain reads immune signals to drive behavior
Matt MillerAdam Kepecs, PhD, the Robert J. Terry Professor of Neuroscience at WashU Medicine, has been awarded the NIH Director’s Pioneer Award, to explore how the brain interprets immune system signals and how they contribute to psychiatric conditions such as depression. The award is given by the National Institutes of Health (NIH) to promote “high-risk, high-reward” research.
Adam Kepecs, PhD, the Robert J. Terry Professor of Neuroscience and a professor of psychiatry at Washington University School of Medicine in St. Louis, has been selected for a National Institutes of Health (NIH) Director’s Pioneer Award, to study how the brain’s neural circuits decode signals from the immune system and orchestrate adjustments in behavior and motivation. The prestigious award, from the NIH, is designed to support high-risk, high-reward research. As part of the honor, the Kepecs lab will receive a total of $3.5 million in funding over five years.
A BJC Investigator at WashU Medicine, Kepecs is renowned for his work on brain circuits involved in cognition and decision making, and how these circuits can produce psychiatric symptoms. The Pioneer Award will support his pursuit of an intriguing hypothesis: that immune signals, such as cytokines, are sensed by brain circuits and contribute to mood disorders such as depression.
“We are thrilled Dr. Kepecs has received this impressive honor from the NIH,” said Linda Richards, PhD, the Edison Professor and head of the Department of Neuroscience at WashU Medicine. “Dr. Kepecs is an innovative and creative thinker, and this work in particular has enormous potential to change our understanding of how immune signals may be sensed by specific cells and circuits in the brain to impact cognition and behavior.”
Kepecs’ team will map immunoceptive circuits — the brain pathways that detect immune signals — and translate them into behavioral responses. While immune signals such as inflammatory cytokines can trigger protective behaviors during acute illness, they also may drive long-term changes in mood and motivation in chronic inflammatory conditions.
The genesis of this work is the influence the immune system has on our behavior when we are sick. Fever, nausea, vomiting, and the desire to crawl into bed and never leave are the unpleasant but necessary tools the body uses to cope with and outlast an infection. The physical symptoms of fever and vomiting have known neurological triggers that respond to the presence of infection-fighting molecules, called cytokines, from the immune system. The psychiatric crawl-into-bed symptoms such as apathy and depression also may be triggered by cytokines, according to Kepecs.
By pursuing how the immune system interacts with neural circuits that are involved in psychiatric disorders, Kepecs and his lab are sailing into unfamiliar waters, seeking to discover how conditions such as depression emerge – and perhaps how to alleviate them.
“If we can identify the relevant neural circuits, we can gain insight into how the brain communicates with the immune system,” said Kepecs, “and open immediate opportunities for developing targeted drugs for depression and related conditions.”
The research uses cutting-edge technologies for whole-brain mapping, cellular-resolution activity tracking, and precise manipulations of neural circuits.
In previous research, Kepecs has pioneered the understanding of how the brain calculates confidence in decisions, treating confidence not as a vague feeling but as a measurable process rooted in neural circuits. His team demonstrated that confidence reflects a probability calculation — how likely one is to make the right choice based on evidence. By studying this in humans and rodents, the researchers identified specific brain circuits and cell types that perform these calculations, with implications for psychiatric disorders including anxiety and compulsive behavior.
Building on this foundation, Kepecs has shown how computational analysis of behavior can provide an objective framework to study mental dysfunctions and link human to animal behavior for deeper mechanistic insights. This approach paves the way for more precise diagnoses of psychiatric conditions. In one study, Kepecs’ lab identified brain circuits responsible for hallucination-like perception in rodents, with the goal of translating these findings to better understand psychosis in humans.
Kepecs was named a BJC Investigator in 2019 and has been recognized for excellence in research as a Kavli Frontiers of Science fellow, a John Merck Scholar, a Klingenstein Fellow and an Alfred P. Sloan research fellow. He also has been awarded the McKnight Foundation Memory and Cognitive Disorders Award.
