Current Safar Lab Research

The Safar Lab basic and translational research targets three crucial problems of structural biology of age-related neurodegenerative disorders:


The Molecular Basis of Age-Related Dementias.
The Safar Lab developed a battery of ultrasensitive new tools for investigating the mechanism of misfolding of major proteins causing AD, AD-related dementias (ADRD), and prion diseases directly in human brains. Through methods such as conformation-dependent immunoassay (CDI), conformational stability assay (CSA), conformation-sensitive mass spectroscopy (MS), fluorescence spectroscopy, and cryo-Electron Microscopy (cryo-EM), the laboratory ultimate goal is to elucidate the structure of disease-causing distinct misfolded forms — strains — of human brain-derived amyloid beta, tau, and prions.


The Role of Prion-Like Strains of Misfolded Proteins in Phenotypic Diversity of Neurodegeneration.
Using human brain isolates, transgenic models, and cell cultures, these projects focus on improving our understanding of the molecular mechanisms governing the phenotypic heterogeneity and progression rates of AD and prion diseases, specifically on different prion-like strains of small oligomers (SOs) of Amyloid beta, tau, and pathogenic prion protein.


The Interactomes of Prion-Like Strains of Misfolded Proteins on Distinct Genetic Backgrounds.
The goal of these studies is to delineate the impact of prion-like strains of amyloid beta and tau upon the AD phenotype in the context of specific risk genes using proteomic profiling of amyloid plaques, neurofibrillary tangles, glia, and neurons. This insight is critical for efforts to characterize key factors responsible for the very rapid rate of cognitive decline in some subtypes of AD and ultimately to novel therapeutic strategies to slow AD progression.