The Brain and Behavior Research Foundation (BBRF) is the largest private funder of mental health research grants, dedicated to alleviating suffering caused by mental illness by supporting scientific discoveries that advance prevention, diagnosis, and treatment.
This year, Elizabeth Doncheck, Ph.D., assistant professor in the Department of Neurobiology, has been selected to receive a 2026 BBRF Young Investigator Grant.
"Receiving the Brain and Behavior Research Foundation's Young Investigator Award is particularly meaningful to me, both professionally and personally," said Doncheck.
"Professionally, it provides critical support for my research program at a pivotal stage in my career. Personally, it affirms a mission that has become central to my work: advancing public health while addressing longstanding gaps in biomedical research. For decades, females have been understudied in neuroscience and biomedical studies, often based on the assumption that biological variability associated with hormones would complicate findings. Increasingly, however, we're learning that studying those biological differences doesn't just improve our understanding of females; it can reveal fundamental neurobiological mechanisms that may benefit everyone."
The Doncheck Lab studies how neural activity patterns shift to influence executive function and motivated behavior. A major focus of the lab is substance use disorder, where relapse vulnerability and the underlying neural circuit activity vary across individuals and over time, defying simple, one-size-fits-all explanations. By understanding these dynamic influences, the lab aims to translate basic neuroscience discoveries into more precise and effective interventions.
With support from the BBRF award, Doncheck's lab will investigate the neurobiological mechanisms underlying relapse vulnerability in opioid use disorder, focusing on how naturally fluctuating hormone levels shape brain activity to either increase or reduce relapse risk, and whether those effects differ across sexes.
"A large body of research indicates that elevations in estrogen promote relapse whereas elevations in progesterone protect against it in females," said Doncheck. "Understanding this pendulum-like relationship provides a unique opportunity to identify not only how relapse is promoted, but also the brain mechanisms that may override that."
Doncheck points to the prefrontal cortex, the brain region responsible for executive control and decision-making, as a key site where these hormones exert their effects. She previously discovered that estrogen could act within this region to promote relapse and her research is now revealing progesterone can act therein to suppress it. As she also recently discovered activation of specific neurons in the prefrontal cortex can drive relapse, her lab is now investigating whether estrogen and progesterone sway the activity of those neurons.
"It remains unknown whether these hormones converge on the precise neuronal ensembles that drive relapse, and whether those ensembles serve as the biological substrate through which estrogen and progesterone exert opposing effects," said Doncheck. "To address that question, our lab will use state-of-the-art techniques that allow us to simultaneously visualize and manipulate these neuronal ensembles during relapse testing in the presence of estrogen, progesterone, and both hormones together."
Importantly, the lab's emerging data suggest that progesterone's protective effects may not be limited to females.
"For a long time, males were treated as the default model in biomedical research, with discoveries in males assumed to generalize broadly," said Doncheck. "What is exciting about these findings is that they suggest the reverse may also be true. By studying neurobiological mechanisms that were first revealed through research in females, we may uncover treatment strategies that ultimately benefit both sexes. These studies highlight that inclusion is not simply about representation; it's also about discovery."
Because the prefrontal cortex plays a broad role in executive function, Doncheck believes the implications of this work may extend well beyond substance use disorder. Depression, anxiety, and other psychiatric illnesses are frequently characterized by executive dysfunction, are influenced by ovarian hormones, and commonly co-occur with substance use disorders.
"The data generated through the Young Investigator Award may open entirely new avenues of investigation into whether these mechanisms contribute to other neuropsychiatric disorders," said Doncheck.
She also notes that the findings could have unusually rapid translational potential.
"One of the most exciting aspects of this work is that there are already FDA-approved medications that target the signaling pathways through which we believe progesterone exerts its protective effects against relapse," said Doncheck.
"If these mechanisms continue to hold up, it raises the possibility that existing medications could be repurposed or cross-listed as relapse-prevention therapies. Discoveries that began by understanding hormone-sensitive mechanisms in females could therefore lead to practical treatment strategies for both women and men, helping move promising neuroscience findings from the laboratory to the clinic much more quickly."