Carney Institute grants more than $900,000 in innovation awards to Brown University researchers

By Gretchen Schrafft

Eight projects will be supported this year, with four fueling research at the Center for Alzheimer’s Disease Research. Each represents bold, promising brain science at Brown.

The lab of Sonia Mayoral, one of the recipients of this year's Zimmerman Innovation Awards in Brain Science, uses this culture of oligodendrocyte precursor cells and neuronal axons to study myelination, a process that holds answers about diseases like Alzheimer's and multiple sclerosis. Her project builds off research supported by one of the very first innovation awards, granted 11 years ago.

The Robert J. and Nancy D. Carney Institute for Brain Science will provide $928,000 in seed funding for eight high-impact brain science research projects led by 12 Brown faculty members.

Now in its 11th year, the Zimmerman Innovation Awards in Brain Science jump-start promising, risky research, giving scientists the proof of concept they need to secure long-term funding from government, nonprofit or industry sources. It’s a formula with an impressive track record: as of fall 2024, brain science investigators who received a total of $4.9 million in innovation award funding had gone on to earn $166 million in external funding. This cycle of awards brings the institute’s total innovation award investment to $5,800,000.

This year, the institute will fund eight projects. Four projects will receive a total of $496,000 to address important questions from across the breadth of brain science. Another four will receive $432,000 to advance research that targets Alzheimer’s disease and related dementias.

Oriel FeldmanHall, pictured here together with her lab (center middle), is one of the recipients of of a Zimmerman Innovation Award in Brain Science this year.

Diane Lipscombe, Reliance Dhirubhai Ambani Director of the Robert J. and Nancy D. Carney Institute for Brain Science, said the awards support research that is exciting, timely and in need of proof of principle data.

“Each year I am more and more impressed by the creativity of our brain science community at Brown. This year, awardees are developing new tools to gain essential information for neurodegenerative diseases as well as applying the trans-Tango tool - developed with funds from this program - to study myelin, the electrical insulator in the nervous system,” Lipscombe said. “Other projects explore brain mechanisms that help humans solve learning problems in their social worlds, and the role of gut-brain communication in early-life stress.”

Bess Frost, Salame-Feraud Director of the Center for Alzheimer’s Disease Research, said Alzheimer’s disease won’t be eradicated through any one approach - which is why the innovation awards are so vital.

“These awards, all of which went to groups who were in some way collaborating across scientific disciplines, are coming at the research from many directions,” Frost said. “These big, bold approaches are a direct result of the diversity of the teams.”

The Carney Institute invests up to $100,000 per project for one year, renewable for a second year on a competitive basis. Projects led by a junior faculty member are eligible for an additional $32,000 in funding.

Below are the projects funded by this year's innovation awards.

Your brain on iron: Sarah Thomas's new imaging method will assess brain tissue iron in teens using cannabis.

A multimodal evaluation of adolescent cannabis use disorder: testing neurobehavior change over time

Investigator: Sarah Thomas, assistant professor of psychiatry and human behavior (research)

Adolescents who use cannabis progress more quickly toward cannabis use disorder than adults, but it is difficult to study neurobiological adaptations because the standard imaging technique, positron emission tomography (PET), isn’t safe for adolescents. Sarah Thomas has made a discovery that will enable her to safely study adolescents: teenagers who use cannabis have significantly lower brain tissue iron, measured with magnetic resonance imaging and representing dopamine neurophysiology, than teenagers who don’t. Through the innovation award, Thomas will use this unique imaging technique to track brain tissue iron levels in adolescents across a three month period to gather data about the development and progression of use disorders. “Our results have the potential to not only establish a safe way to study neuroadaptations in adolescent cannabis use–they could also help us understand how cannabis use's impact on dopamine may give rise to depressive and psychosis symptoms, which is a risk that happens when starting cannabis use during adolescence,” said Thomas.

Characterizing the contents of neural replay for social navigation

Investigators: Oriel FeldmanHall, Alfred Manning Associate Professor of Cognitive and Psychological Sciences, and Apoorva Bhandari, assistant professor of cognitive and psychological sciences (research)

Researchers have established that rodents “replay” their memories of traversing mazes while resting or sleeping to build cognitive maps that help them navigate those mazes in the real world. In a paper published in 2024, cognitive neuroscientists FeldmanHall and Bhandari established through human experiments and computational modeling that humans do something related but much more abstract: replay their memories of daily social interactions to build a map of social networks and successfully maneuver within society. Through the innovation award, FeldmanHall and Bhandari now seek to uncover the contents of this social neural replay–something that is extremely difficult to do because the neural signals involved are very hard to detect even with the most sophisticated methods. Using a new analysis technique they designed, the team will attempt to isolate the content of what human brains are replaying in fMRI data recorded during rest breaks subjects take in between performing a complex social navigation task. “Our project stands to provide a major contribution to our knowledge base of how people solve learning problems in their social worlds,” said the team.

Antibiotics heat things up: these heatmaps show early-life-stress mice navigating a maze with and without antibiotic treatment. Thanks to the antibiotics, mice spend more time in all arms of the maze, indicating a reduction in their anxiety-like behavior.

Microbial pathways of early life stress-induced anxiety

Investigator: Peter Belenky, associate professor of molecular microbiology and immunology

Can the gut-brain axis—the bidirectional communication between the central and enteric nervous systems—help explain how early-life stress leads to long-lasting anxiety? The Belenky Lab has leveraged a mouse model of early-life adversity to investigate this question. With the innovation award, the lab will explore how altering the gut microbiome—through treatments such as antibiotics—can influence anxiety-related behaviors. “Understanding the precise relationship between the gut microbiome and anxiety symptoms could pave the way for new microbiome-based interventions and diagnostics for stress-related disorders,” said Belenky.

Myelin trans-Tango: a new tool for labeling myelinated neurons

Investigator: Sonia Mayoral, Robert J. and Nancy D. Carney Assistant Professor of Neuroscience

Myelin in the spotlight: oligodendrocyte precursor cells (blue nuclei) express a modified version of the *trans*-Tango ligand (pink) as a first step in developing a new tool for labeling myelinated neurons.

Through the innovation award, Sonia Mayoral, an expert on myelin, will build a new, critically important tool. Myelin is a fatty substance made by glial cells that form around nerves. Scientists have known for a long time that myelin greatly increases the speed at which messages, in the form of electrical signals, pass between neurons. Only more recently have researchers realized that myelin also plays important roles in a host of other brain processes, including learning and memory, but they have not been able to study how myelin is involved because no tool for identifying myelinated neurons currently exists. Through a partnership with colleague Gilad Barnea, who used one of the earliest innovation awards to develop a suite of tools for tracing brain circuit communication called the trans-Tango toolkit, Mayoral will adapt aspects of trans-Tango to instead label myelinated neurons. “These mechanisms are extremely important to uncover since their discovery can lead to better therapies for neurodegenerative diseases where myelination is disrupted, like multiple sclerosis and Alzheimer’s disease,” said Mayoral.

Alzheimer’s disease and related dementias

A sweet new suite of techniques for studying Alzheimer's disease: Lee and Moore have hit upon a brand new way to measure how important a blood vessel is to a network of vessels.

The intelligent typology hypothesis of late onset Alzheimer’s disease: early failure in vascular graph fitness driven by impaired endothelial calcium dynamics

Investigators: Jonghwan Lee, associate professor of engineering and brain science, and Chris Moore, professor of neuroscience and brain science

Lee, an expert on imaging and analysis of brain microvasculature, has discovered that mice with the leading genetic risk factor for Alzheimer’s disease, APOE4, have vascular systems that look strikingly different from the vascular systems of normal mice. These differences have potential both for early diagnosis and as a therapeutic target, since they manifest much earlier than the disease onset and may have etiological roles in later pathological hallmarks of the disease. Here, he teams with Moore, an authority on various biological roles of microvasculature, to test a new novel hypothesis regarding the origins of this change. Through the innovation award, the team will use the latest imaging techniques, lab-built deep learning networks and graph theory to test their hypothesis that the gene APOE4 causes these vascular differences. “If our hypothesis proves correct, this opens up a totally new area of focus for Alzheimer’s disease research as well as a new suite of techniques that enables researchers to study it,” said the team.

Discovering and interpreting novel biomarkers of Alzheimer’s disease progression in longitudinal MEG data

Investigator: Stephanie Jones, professor of neuroscience

Magnetoencephalography (MEG) is a noninvasive device that measures the magnetic fields produced by the brain’s electrical signals. The Jones Lab is on the cusp of being able to predict, by interpreting MEG data, whether or not a patient presenting with symptoms of mild cognitive decline will advance to Alzheimer’s disease two and a half years later–an incredibly complex computational feat. The innovation award will allow Jones and her team to hone their technique while working with a massive longitudinal MEG dataset comprising the results of hundreds of patients over multiple years, provided by her collaborators at the University of Madrid. “Refining the predictive power of our technique has the potential to turn magnetoencephalography from a purely diagnostic tool into one that can be used to actively diagnose and treat patients with symptoms of cognitive decline. Our ultimate goal is to delay or prevent progression to Alzheimer’s disease,” said Jones.

Ovaries could hatch answers: the ovaries from a control and Alzheimer's disease mouse model, with the nuclei of all cells in blue and developing eggs in red.

Defining the role of the hypothalamic-pituitary-ovary axis in the initiation and progression of Alzheimer’s disease

Investigator: Gregorio Valdez, GLF Translational Associate Professor of Molecular Biology, Cell Biology and Biochemistry, Richard Freiman, professor of molecular biology, cell biology and biochemistry and professor of obstetrics and gynecology

Women are twice as likely to develop Alzheimer’s disease, but the reasons for this are understudied. Through an innovation award granted two years ago, Freiman and Valdez made a breakthrough: in female mice with Alzheimer’s disease, the ovaries, pituitary gland and hypothalamus weren’t communicating with each other like they normally would. Now, the team will use this new innovation award to explore whether the disruption of endocrine signaling between the ovary, pituitary and hypothalamus may be a helpful predictor of Alzheimer’s disease. In addition, by studying female mice with the premature onset of menopause, they will determine if any symptoms of Alzheimer’s disease appear earlier than expected. “Outcomes of this research will potentially identify new predictive biomarkers related to Alzheimer’s disease, but also may reveal new targets for therapeutic interventions that block or slow progression of the disease in women,” said the team.

The role of retrotransposon activation in the etiology of Alzheimer’s disease and related dementias

Investigators: John Sedivy, Hermon C. Bumpus Professor of Biology, and Sukanta Jash, assistant professor of molecular biology, cell biology and biochemistry (research)

Retrotransposons are viral-like DNA sequences found throughout the human genome that are largely benign in healthy young individuals but, during diseases like Alzheimer’s, can become active and, like viruses, promote inflammation. Retrotransposons are related to the human immunodeficiency virus (HIV), and a few years ago Sedivy, an expert in this area, proposed that their inflammatory effects in Alzheimer’s disease could be targeted with drugs developed to treat HIV. An important missing link has been a test that could show that these drugs were controlling retrotransposons in patients. Through the innovation award, Sedivy and Jash, an expert on stem cells and RNA vaccine technologies, are teaming up to develop such a test. “If successful, this project will develop tools to enable researchers to determine whether drugs, either repurposed HIV drugs or completely new ones, are hitting and controlling the intended target. Those tools will also be critical for eventual FDA approval,” said the team.