Scott A. Small, MD, leads a lab focused primarily on disorders that affect the hippocampal circuit and whose work is organized around the principle of ‘regional vulnerability.’ He hypothesizes that different regions of the hippocampal circuit are vulnerable to different disorders, and that pinpointing these vulnerable regions can therefore provide pathogenic insight. Accordingly, Dr. Small’s lab has optimized and applied high-resolution variants of fMRI to patients and pre-clinical models, establishing patterns of regional vulnerability within the hippocampal circuit linked to Alzheimer’s disease, normal cognitive aging and schizophrenia. In subsequent imaging-guided molecular investigations, studies have implicated retromer in Alzheimer’s disease, CREB-dependent histone acetylation in normal aging and glutamate catabolism in schizophrenia. Most recently, Dr. Small has relied on this pathogenic insight to begin drug discovery projects for each hippocampal-based disorder. Interestingly, retromer has also been implicated in Parkinson’s disease, and his lab is testing retromer drugs in model systems. To accommodate these MRI-to-molecular studies, Dr. Small’s program is divided into an imaging lab, housing analytic tools and a model MRI scanner, and a ‘wet’ lab where they perform cellular/molecular studies.