Dr. Brielle Ferguson
Assistant Professor Harvard Medical School
Postdoctoral Researcher Stanford University
PhD Drexel University
The fundamental belief that science can be used to improve people’s lives is at the heart of Dr. Brielle Ferguson’s research program. But she didn’t always feel that way. As a kid, Brielle didn’t hold any particular fondness for science over her other classes. It didn’t really click with her what one could actually do with science or research until she started to learn about neuroscience as an undergraduate. Only then did she begin to see the potential of neuroscience to reveal the secrets of human cognition and to inform new interventions for those living with neurodevelopmental and neuropsychiatric disorders. As an Assistant Professor of Genetics and Neurology at Harvard Medical School and Boston Children’s Hospital, she is turning this potential into a reality through her research on the prefrontal and thalamocortical circuitry underlying cognitive function and dysfunction.
Brielle started her undergraduate education on a pre-med track but, like her experience with science more broadly, it wasn’t clicking. She pivoted towards psychology, which drew her in with questions about the human mind and behavior. She started doing research in a psychology lab that she really enjoyed, but still, something was missing. She felt like she wanted to delve deeper, but didn’t yet know what that really meant or how it might be achieved. That is, until she found herself in her first neuroscience course. Her professor, Dr. Brian Wiltgen, described experiments with cells that were tagged by recent or remote memories and made to “glow”. Brielle was captivated – it seemed that neuroscience could provide a route for probing more deeply into questions of the brain and behavior in just the way she was craving. She approached Dr. Wiltgen about volunteering in his lab, and so began her “love story with neuroscience”.
Brielle had already been considering applying to psychology PhD programs, so once she fell in love with neuroscience, she reset her sights on neuroscience programs. She applied and was accepted to the Neurosciences PhD program at Drexel University to work with Dr. Wen-Jun Gao, who was studying the neural mechanisms of cognitive symptoms in neuropsychiatric disorders. Brielle had a long-standing interest in neuropsychiatric disorders; she had a relative with schizophrenia and had always had countless questions about his condition that, to her frustration, no one could fully answer. Now, as a neuroscientist-in-training, Brielle hoped to answer some of those questions through her PhD research. Many of those questions had previously centered around “positive” symptoms of schizophrenia like psychosis, but in the Gao lab, she focused her research on some of the “negative” symptoms – cognitive deficits like attentional and working memory impairments. The prefrontal cortex (PFC) is thought to control these sorts of cognitive abilities, and Brielle became especially interested in its interactions with another brain structure called the mediodorsal thalamus (MD) that provides substantial input to the PFC. Still in the early days of chemogenetics, Brielle pioneered using inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to suppress MD activity in mice and test the consequences on prefrontal circuitry in a slice preparation and on behavior. She found that chemogenetic MD suppression strongly reduced inhibitory signaling in the PFC and impaired working memory, attentional flexibility, and social interactions. She went on to show that chemogenetic activation of parvalbumin-positive inhibitory neurons (PVINs), a major target of MD inputs, was sufficient to restore both circuit and behavioral phenotypes to normal even while MD was suppressed. Excitingly, the drug Zolpidem that activates receptor targets of these PVINs and is already clinically approved for treating sleep disorders had similarly ameliorative effects. Thus, cognitive deficits might arise when MD does not properly engage PVINs in PFC, and they may be a promising target for clinical intervention.
While presenting her work at the Annual Biomedical Research Conference for Minoritized Scientists (ABRCMS), Brielle met Dr. John Huguenard, a Stanford neuroscientist who had spent much of his career studying related circuit mechanisms underlying epilepsy. He asked whether she’d given much thought to how her findings might relate to seizure-independent cognitive deficits in epilepsy. She had not, but this piqued her interest enough that she accepted a postdoctoral position in his lab to study this very question. Using a genetic mouse model of absence epilepsy and homemade operant chambers for automated behavioral measurements, Brielle found that these mice exhibit attentional impairments that, as in the MD-suppressed mice from her PhD, were caused by PVIN dysfunction and could be rescued by PVIN stimulation. Thus, PVINs seemed to be a common culprit responsible for cognitive dysfunction in different mouse models of neurological disorders.
At this point, Brielle could envision leading a team of scientists trying to understand the circuits underlying thinking, planning, and decision making, and how those circuits can malfunction in disease using rodent models. Although she didn’t feel that necessarily had to be in an academic context, academia proved to be the best option for her. She accepted a faculty position at Harvard Medical School and Boston Children’s Hospital, where her lab would be situated in a unique environment where basic researchers and clinician scientists intermix. A big draw for her was the previously established infrastructure to support and foster interdisciplinary collaborations that bridge basic and translational science. Brielle’s new lab, which she began in 2023, seeks to understand how PVINs in the prefrontal cortex contribute to cognitive functions and the extent to which the thalamus – including her old friend, MD – might be disrupted across different disease states with attentional dysfunction. In the spirit of her new department, she is working to identify biomarkers of cell type- and circuit-specific activity patterns that she hopes can be assessed non-invasively in humans, e.g. with electroencephalography (EEG). In this way, she aims to be able to pinpoint cellular- and/or circuit-level targets for interventions to help improve attentional and other cognitive impairments in people living with these impairments.
At the same time that she has been laying the scientific groundwork for her current position and research program, Brielle has also built communities, both locally and globally, to support minoritized scientists. She reflects that science is hard for a multitude of reasons, and for her, finding other Black scientists has been crucial to help her push through the hard bits at every stage of her training. In graduate school, for instance, a particularly formative experience was the first time she saw another Black scientist - Dr. Kafui Dzirasa from Duke – give a talk at a conference. Although this wasn’t until she was a full four years into her PhD, it was a pivotal experience for Brielle, helping her to envision that she, too, could make a successful career in this field. As a postdoc, Brielle found fulfillment, support, and lifelong friendships in the Black Postdoc Association at Stanford, in which she also served as Co-President. During the height of the Covid pandemic and Black Lives Matter movement in the summer of 2020, Brielle also helped co-found Black In Neuro. Black In Neuro has had an immeasurable impact on the neuroscience community as a whole, but especially on Black neuroscientists by fostering an international community. This has been achieved in large part through organizing global, virtual events (e.g., Black In Neuro Week) and extensive other programming that Brielle has overseen in her role as Programs Director. From doggedly pursuing the neural mechanisms of attention and cognition since her first meet-cute with neuroscience, to bringing together communities of Black scientists on both local and global scales when the field’s lack of diverse representation made such communities feel scarce, Brielle has shown herself to be a force of nature. Without a doubt, her pursuit of goals for her own lab will yield similarly impressive and impactful outcomes.
Find out more about Brielle and her lab’s research here.
Listen to Megan’s full interview with Brielle on March 27, 2024 below!
