Brain Resilience Lab

Welcome to the in-house research hub of the Knight Initiative, where we push what’s technologically possible in the field of resilient brain aging.

Who We Are
As the research engine of the Knight Initiative for Brain Resilience, our in-house lab combines academic rigor and curiosity with the agility of a startup. We leverage state-of-the-art technologies—such as transcriptomics, proteomics, metabolomics, and advanced imaging—to explore and map the molecular evolution of brain aging across the lifespan.
With a flexible, data-driven approach, we both spearhead new discoveries and rapidly engage with emerging breakthroughs, accelerating progress in the science of brain health and resilience.

Our Research
What promotes healthy brain aging, and how can we protect against neurodegeneration? Our research focuses on answering these crucial questions by using cutting-edge omics technologies and pioneering methods to map the molecular changes in the brain throughout the aging process.
By revealing the underlying mechanisms of aging, neurodegenerative diseases, and cognitive decline, we aim to pave the way for new strategies to maintain brain health across the lifespan.

Flagship Projects
One of our key flagship projects is the Brain Aging Census, where we perform unprecedented sampling of 100 brain regions from brains spanning multiple decades of life, representing most anatomically defined areas. This comprehensive approach allows us to explore the molecular landscape and identify factors involved in brain aging and neurological diseases. Using RNA sequencing (RNA-seq), spatial transcriptomics, lipidomics, and proteomics, we aim to create a detailed molecular map of the aging brain. This project, in collaboration with the Lieber Institute for Brain Development, leverages the combined expertise of three leading labs specializing in transcriptomics, proteomics, and lipidomics.
Specialized Brain Systems Studies
Our other major projects focus on specialized systems of the brain, such as the vasculature and the choroid plexus, which secretes cerebrospinal fluid (CSF) and helps maintain brain health. We have profiled healthy human brain vasculature from 40 different brain regions and identified several regions where the molecular composition of the blood-brain barrier (BBB) differs from others. In parallel, using advanced single-nucleus RNA sequencing and spatial transcriptomics, we have characterized the cellular organization of the human choroid plexus for the first time. Our findings revealed a specific molecular signature in the choroid plexus vasculature, particularly in pericytes and immune cells of Alzheimer’s patients. These discoveries offer new insights into Alzheimer’s disease pathology and potential biomarkers for early detection and treatment.
Technology Projects
In our technology projects, we are pioneering advanced techniques to enhance our research capabilities. This includes improving high-resolution imaging methods, developing novel bioinformatics tools for data analysis, and creating innovative molecular probes. We have developed an innovative technique that, for the first time, allows us to measure RNA, lipids, and proteins at single-cell resolution within their spatial context in human brain samples. These advancements are crucial for studying brain function and pathology in unprecedented detail, enabling the precise and comprehensive analysis needed for our flagship and collaborative projects.
Collaborative Projects
Our collaborative projects involve partnerships with other research institutions and laboratories to integrate multidisciplinary expertise. These efforts collectively aim to enhance our understanding of brain biology, aging, and neurodegenerative diseases, paving the way for new therapeutic strategies and technological innovations.