Marcos Otero-Garcia, PhD

Changes in brain cellular and molecular architecture are fundamental to aging and disease. These intricate spatial patterns have limited our ability to decipher neurodegenerative processes. However, recent advances in single-cell and spatial omics methods present an opportunity to advance our understanding of the mechanisms underlying the progression of neurodegenerative diseases.

I am deeply interested in technological innovation and neurodegenerative disease, particularly the development of spatial omics methods to study tau pathology in Alzheimer’s disease. During my postdoctoral training at UCLA and Stanford, we designed novel methods for unbiased single-cell profiling of human brain tissue. Our approach revealed specific neuronal cell types susceptible to tau pathology and the molecular signatures associated with neurofibrillary tangles in Alzheimer’s disease patients. However, single-cell sequencing protocols compromise important spatial context. To fill this gap, I joined industry efforts to create spatial omics technologies capable of interrogating hundreds of gene targets in intact tissue sections, and applied them to study brain development, neurodegeneration, and demyelination in mouse models. I subsequently returned to academia to pursue an independent research program focused on tau pathology in Alzheimer’s disease.

I am currently using single-cell and spatial omics approaches to study the progression of neurofibrillary pathology in Alzheimer’s disease. My goal is to create innovative tools and generate insights that advance our understanding of neurodegenerative processes, identify therapeutic targets, and improve human health.

In Philip L. De Jager’s group, my work integrates single-cell and spatial transcriptomics and proteomics to define how tau pathology disrupts cellular programs as it spreads across interconnected brain regions in Alzheimer’s disease, while contributing to large-scale efforts to generate a high-resolution spatial atlas of the aging brain.