Pain, Alzheimer’s and more: the Wu Tsai Neurosciences Institute announces its sixth round of seed grants
The Wu Tsai Neurosciences Institute has awarded its sixth round of seed grants to five interdisciplinary research teams taking on important questions in neuroscience.
For the past decade, the Neurosciences Seed Grant program has fostered dozens of high-risk but potentially high-reward ideas in neuroscience. This year’s crop includes efforts to develop new tools for delivering drugs to the brain; study the role of neuropeptide molecules in pain and brain signaling; and probe the links between genetics, inflammation, and Alzheimer’s disease. In all, ten labs from nine departments in the Schools of Humanities and Sciences, Medicine, and Engineering will take part in the research projects.
For the second time, the Knight Initiative for Brain Resilience will co-sponsor a project. This latest one is aimed at uncovering links between genetics and an immune system overreaction that plays a role in Alzheimer’s disease. Previous co-funded projects focused on studying a potential target for Alzheimer’s treatments and understanding how the gut and the brain communicate in Parkinson's disease.
"We are all excited to see the discoveries that emerge from these teams and how their work shapes the future of neuroscience at Stanford."
Lisa Giocomo
Professor of Neurobiology and Wu Tsai Neurosciences Institute Executive Committee member
Another project, led by Elizabeth Mormino, a research associate professor of neurology and neurological sciences at Stanford Medicine and Vinod Menon, a professor of psychiatry and behavioral sciences at Stanford Medicine, will focus on developing new AI tools to better predict the progression of Alzheimer’s disease.
“There is an urgent need to understand factors that cause clinical dementia,” Mormino said. “For instance, some individuals have biological signs of Alzheimer’s disease yet stay cognitively intact and high functioning, while others experience dementia and lose the ability to complete everyday activities.”
Mormino, Menon, and their teams will look for signatures of resilience using artificial intelligence and a range of imaging and biological datasets.
“Our collaboration unites psychiatry and neurology faculty, whose complementary expertise is essential for developing a comprehensive framework of brain resilience in aging,” Menon said. “This funding will enable us to establish the foundational data and methodological infrastructure we need to secure larger funding focused on mechanisms of resilience in Alzheimer’s disease and throughout the aging process.”
Lisa Giocomo, a professor of neurobiology and one of Wu Tsai Neuro’s deputy directors, chaired this year’s selection committee. She said the committee’s decisions were particularly tough this year given the number of outstanding proposals they read.
“This year’s selected recipients stood out for their creativity, collaboration and transformative potential,” she said. “The seed grants program provides a unique opportunity for our community to form bold collaborations that have the potential to open new scientific directions. We are all excited to see the discoveries that emerge from these teams and how their work shapes the future of neuroscience at Stanford.”
Funded Grants
Impaired RNA Editing as A Cause of Neuroinflammation in Alzheimer's Disease*
Lead Investigators
Jin Billy Li, Professor of Genetics (School of Medicine)
Marius Wernig, Professor of Pathology (School of Medicine); Co-Director of the Institute for Stem Cell Biology and Regenerative Medicine
Genetics plays a crucial role in Alzheimer’s disease, but researchers don’t fully understand the specific mechanisms involved. At the same time, recent research suggests brain immune cells called microglia can become overactive in Alzheimer’s, triggering inflammation that damages neurons and exacerbates cognitive decline. Drawing on brain-like cells derived from human stem cells in the laboratory, Li and Wernig will investigate a process known as RNA editing that may connect genetics to microglial overreaction. Their findings could provide new insights into Alzheimer’s disease and inform potential therapies.
*Co-sponsored by the Knight Initiative for Brain Resilience
3D optical reconstruction of whole-brain neuropeptidergic connectome in Caenorhabditis elegans
Lead Investigators
Rongxin Fang, Assistant Professor of Neurosurgery (School of Mediciner)
Kang Shen, Professor of Biology (School of Humanities and Sciences and of Pathology (School of Medicine), Vincent V.C. Woo Director, Wu Tsai Neurosciences Institute
Electrochemical links called synapses are crucial for communication between neurons in the brain, but they represent only one way brain cells talk to each other. Another form of communication involves more diffuse chemical messengers—particularly neuropeptides. Using optogenetics and machine learning, Fang and Shen will study these messengers in worms called C. elegans. The resulting data will help uncover how this sometimes-overlooked communication system drives gene expression at the organism level.
Elucidating Neurobiological and Exposomic Mechanisms of Human Brain Circuit Resilience to Aging and Tauopathies: An AI-driven modeling approach
Lead Investigators
Vinod Menon, Professor of Psychiatry and Behavioral Sciences (School of Medicine)
Elizabeth Mormino, Associate Professor of Neurology and Neurological Sciences (School of Medicine)
Menon and Mormino’s project will develop an innovative artificial intelligence framework to help discover why some people withstand aging and Alzheimer's disease better than others. By analyzing brain scans and biological data from over 22,600 individuals, the pair will create computational models that can predict how well someone's brain might resist age-related decline or the protein accumulations associated with Alzheimer's disease. The insights gained could transform how we understand brain aging and lead to more personalized approaches for maintaining brain health.
Harnessing circadian rhythmicity at the blood-cerebrospinal fluid barrier with a perfusable biomimetic hydrogel-integrated chip
Lead Investigators
Ryann Fame, Assistant Professor of Neurosurgery (School of Medicine)
Sarah Heilshorn, Professor of Materials Science and Engineering (School of Engineering)
Cerebrospinal fluid (CSF) delivers electrolytes, hormones, neurotransmitters and more to the brain, and it is essential to brain health and development. It’s largely produced by the choroid plexus, which—like pretty much everything else in our bodies—follows a circadian rhythm. To better understand how that rhythm affects the choroid plexus and CSF, Fame and Heilshorn will develop a “choroid plexus-on-a-chip.” This model could help researchers better understand the composition of CSF and design therapies for improving brain health.
Rewiring neuropeptide signaling to therapeutic outcomes with GLumigenetics
Lead Investigators
Michael Lin, Associate Professor of Neurobiology (School of Medicine) and of Bioengineering (Schools of Medicine & of Engineering)
Xiaoke Chen, Associate Professor of Biology (School of Humanities and Sciences)
Chronic pain affects nearly one in four adults in the U.S., yet current treatments like opioids often come with serious risks, including dependence and overdose. Lin and Chen will work to develop a gene therapy system for chronic pain that detects the neuropeptides that drive pain signaling, then rewires them to suppress pain instead. This new technology could offer long-lasting relief without the side effects of current treatments. If successful, it could also help treat other conditions by rewiring how our cells respond to natural chemical signals.
