With the global population aging, understanding how the brain protects itself or becomes vulnerable has never been more urgent. To address this, Stanford researchers are pushing the boundaries of how we understand and preserve brain function across the lifespan.
Since 2022, Catalyst Awards from the Phil and Penny Knight Initiative for Brain Resilience at Stanford's Wu Tsai Neurosciences Institute have supported interdisciplinary teams exploring how sleep, inflammation, endocannabinoid metabolism, cellular stress, microglia, and other factors shape brain aging and resilience.
"These awards brought [biology Professor] Kang Shen and me together to explore a surprising connection between how the nervous system develops and how the same mechanisms go wrong and contribute to neurodegeneration," said Aaron Gitler, the Stanford Medicine Basic Science Professor in the Department of Genetics. "We unexpectedly discovered a new way to make neurons more resilient and found that this is highly conserved [across species]."
Building on this momentum, the Knight Initiative is pleased to announce that four of these projects - including Gitler and Shen's - have been selected to receive additional support through the 2025 Catalyst Momentum Awards. Each team will receive an additional $500,000 over two years to expand or complete their high-impact research.
The 2025 awardees are tackling urgent and complex questions: How do lysosomes, the cell's internal waste-clearing systems, contribute to neurodegeneration? How can we predict and potentially influence how the brain ages over time? How does Parkinson's disease disrupt stored motor memories, and what can be done to preserve them? And how might blocking enzymes called histone deacetylases (HDACs), which help regulate gene activity and cellular stress responses, strengthen the brain's natural protective networks?
"[The Knight Initiative] is bringing together scientists from diverse backgrounds - ranging from molecular and cellular to systems neuroscience - in bold, cross-disciplinary collaborations," said Momentum awardee Jun Ding, an associate professor of neurosurgery and of neurology and neurological sciences, whose team is exploring a new theory of Parkinson's Disease, and a new approach to intervention.
Another cross-disciplinary team is connecting experts in genetics, bioengineering, psychiatry, and data science to apply artificial intelligence to better understand how cognitive abilities change with age and what distinguishes more resilient brains. "We are excited about the scientific direction of our project because it provides a new way of studying cognitive resilience by stratifying individuals by their behavioral trajectories," said project lead Anne Brunet, the Michele and Timothy Barakett Endowed Professor in the Department of Genetics.
One team, led by Monther Abu-Remaileh, an assistant professor of chemical engineering and of genetics and Sarafan ChEM-H Faculty Scholar, aims to integrate innovative large-scale molecular analysis and biochemically targeted interventions to rejuvenate cellular waste clearance at the lysosome, protect against neurodegeneration, and enhance brain resilience. "By understanding how lysosome damage leads to cell death, we hope to have a better understanding of the onset of disease," said project member Scott Dixon, an associate professor of biology.
With continued investment in these promising ideas, the Knight Initiative aims to enable scientists to build on early discoveries and explore bold research directions. Spanning departments across Stanford's schools of Medicine, Engineering, and Humanities and Sciences, the selected projects reflect the Initiative's commitment to interdisciplinary approaches and new hypotheses poised to challenge conventional thinking about brain aging and neurodegeneration.
"Together, these innovative proposals will pursue transformative ideas outside the mainstream that will advance our mission to extend the healthy lifespan of the human brain," said Tony Wyss-Coray, the D.H. Chen Distinguished Professor of Neurology and Neurological Sciences and Director of the Knight Initiative.
Though unique in approach, each of the four awarded projects contributes to a larger story of understanding how brain resilience and vulnerability manifest across biological scales as we age. From organelles to behavior and gene regulation to brain circuits, these projects reflect the Knight Initiative's ambitious mission to reshape how we study and support healthy brain aging and neurodegeneration.