Charlestown Navy Yard Building 114
114 16th Street
Charlestown, MA 02129
Explore This Lab
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.
Research ProjectsFluorescence lifetime imaging microscopy (FLIM) shows subcellular distribution of the PS1 protein in different conformational states as reflected by altered GFP lifetime in different compartments of the live neuron. Th eneuron was infected with GFP-PS1-RFP construct, and the proximity between GFP (PS1 N-terminus) and RFP (TM6-7 loop domain) was monitored by FLIM. The intensity image represents PS1 expression. The pseudo-color FLIM image shows GFP lifetime as color: Red pixels - close NT-loop proximity, blue pixels - NT and loop far apart.
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