Research

We are interested in the fundamental mechanisms of neurodegenerative diseases. Over the past century-plus, the scientific community has learned of specific proteins that misfold and are deposited in neurodegeneration, and recent discoveries have identified other molecular and cellular actors that seem to play a role in the development and progression of disease. However, despite these advances, robust disease-modifying therapies are lacking. To address this gap, we are examining neurodegeneration from new perspectives and making use of new technologies in our research. Our interdisciplinary work involves neurodegenerative disease biology, genomics, neuropathology, molecular biology, neuroscience, and computational biology.

Somatic mutation in Alzheimer's disease

We are interested in understanding how somatic mutations arise in aging and Alzheimer's disease (AD), and what they can teach us about genotoxic mechanisms in brain cells and the downstream effects. We recently reported the first study of the genomes of individual neurons in AD, identifying disease-related somatic mutation patterns. We are now actively examining specific mechanisms of somatic mutation generation in normal aging and neurodegeneration.

Single-cell genomics technology

We are developing technologies to probe the genome and other features of single cells in the brain, to help us learn about how those cells experience aging and are affected during disease pathogenesis.

Harnessing neuropathology to advance research

We use human tissue to focus our studies on medically relevant questions. We collaborate with tissue banks around the world to drive our research, and Dr. Miller directs the Brigham and Women’s Hospital Brain Donation Hub to enable our patients to contribute to research.


Funding

We are fortunate to have generous support from these organizations to further the mission of our research: