Jorge Sepulcre, MD, PhD

The Sepulcre Lab at Yale School of Medicine studies the organization and function of the human brain using advanced neuroimaging, computational neuroscience, and network-based approaches. The lab investigates how large-scale brain networks support cognition and how these networks are altered by aging, neurological disease, and neuropsychiatric disorders. Dr. Sepulcre’s research integrates functional and structural MRI, PET and other molecular imaging, connectomics, genetics, and network theory to better understand the biological architecture of the human brain.

A major focus of the lab is understanding brain connectivity and large-scale neural networks in health and disease. In neurodegenerative disorders, including Alzheimer’s disease and related conditions, the lab examines how molecular pathology such as amyloid and tau accumulation interacts with brain connectivity and cognitive decline. By integrating neuroimaging with genetic and molecular data, the lab also investigates biological factors that contribute to vulnerability or resilience of specific brain networks.

Over the past 10 years, the Sepulcre Lab has also been involved in developing neuroimaging–genetics approaches to identify and prioritize novel protein candidates for PET tracers. Building on these target-discovery efforts, we also work with a dedicated wet-lab space and team to design, synthesize, and perform early testing of small molecules.

Research opportunities in the lab are particularly relevant to students, including medical students, interested in neuroscience, neurology, biomedical imaging, neurodegeneration, and medicinal chemistry. Students can gain experience connecting clinically relevant questions with quantitative analyses of human brain imaging data and applying modern neuroimaging methods to investigate cognition, aging, and disease.