Molecular mechanisms underlying long-term memory: Insights into Alzheimer’s Disease and Related Dementias.

The primary research goal of my lab is to understand the molecular mechanisms of long-term memory impairments in Alzheimer’s disease and related dementia (ADRD) brains, with a focus on understanding the role of epigenetic machinery in this process. Deficits in cognitive function and memory are a debilitating aspect of neurodegenerative diseases resulting in long-term disability, enormous suffering to individuals and their families, and significant socioeconomic cost. Long-term memory consolidation requires the induction of gene expression in a precise temporal and spatial pattern. Learning-induced gene expression follows this specific pattern, producing transient waves of transcription needed for memory consolidation within specific population of cells. These changes require epigenetic events, including modifications to histones that change the accessibility of DNA. Symptoms common to neurodegenerative diseases, such as ADRD, include impairment of long-term memory due in part to epigenetic and transcriptional dysregulation.

We use molecular, pharmacological, and genetic approaches to understand the molecular mechanism underlying cognitive impairments associated with Alzheimer’s Disease and Related Dementia (ADRD). We use state-of-the-art single-cell/nuclei multi-omics, spatial transcriptomics, native chromatin enrichment, proximity labeling, CRISPR, and AAV-based manipulation of transcription in the mouse brain, pharmacology, and behavioral approaches. These cutting-edge tools allow for defining the single-cell resolution molecular machinery that goes awry in neurodegeneration.