Mechanisms of Disease– and Cell Type–Specific Protein Strains
Protein aggregation underlies a broad spectrum of neurodegenerative diseases, such as Alzheimer’s disease (AD) and related disorders (ADRDs). Accumulating evidence supports the existence of distinct protein “strains” with divergent conformational and biological properties. Yet how these aggregated species differ across neural cell types remains incompletely understood.
Topics of interest in the lab:
The lab is broadly interested in understanding how the conformational strains, maturation, and transmission of proteopathic assemblies differ across neural cell types, with a focus on tau, amyloid-β, and α-synuclein. Our current projects focus primarily on:
Protein strain maturation: Investigating how protein aggregates evolve from early assemblies to mature conformations
Cell type–specific protein strains: Defining how protein aggregates adopt distinct conformational states in neurons and glial cells
Protein strain transmission: Elucidating how aggregated species propagate and template pathology across distinct neural cell types
Confocal Microscopy and EMBER (Excitation Multiplexed Bright Emission Recording)
The Condello laboratory has recently developed EMBER, a fluorescent dye-based imaging platform that enables highly sensitive discrimination of amyloid strains.
This innovative confocal workflow captures full excitation and emission spectra of amyloid-binding dyes and applies unsupervised analytical approaches—including PCA, UMAP, and machine learning–based clustering—to distinguish aggregates based on subtle spectral signatures across microplate assays, intact tissue sections, and individual cells.