An increase in Abeta 42/40 ratio has been implicated in Alzheimer's disease (AD) pathogenesis. We focus on the analysis of gamma-secretase and APP interactions, and examine mechanisms by which various genetic and pharmacological factors modulate Abeta production and/or regulate the precision of APP cleavage by gamma-secretase that leads to a change in A beta 42/40 ratio.
Our laboratory employs state-of-the-art molecular imaging approaches (e.g. FRET, Fluorescence Lifetime Imaging Microscopy) to monitor the conformational changes of a single molecule, or molecular complexes, in different subcellular compartments in intact and/or live cells, both in vitro and in vivo. Novel fluorescence microscopy approaches (e.g., Bi-molecular Fluorescence Complementation, photoactivatable GFP) are complemented by conventional cell biology, and biochemistry approaches, to study molecular mechanisms of AD and to identify potential targets for therapeutic intervention.
Oksana Berezovska, PhD
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