Associate Investigator MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital

Investigator, Assoc Prof (M) Neurology, Mass General Research Institute

Associate Professor of Neurology Harvard Medical School

alzheimer's disease; amyloid beta-protein precursor; glutamates; presenilin/gamma-secretase; synaptic defects; synaptotagmins

Dr. Oksana Berezovska leads the Neurobiology of Alzheimer’s Disease research laboratory at MassGeneral Institute for Neurodegenerative Diseases (MIND). Her laboratory focuses primarily on the cellular and molecular events underlying neuropathological changes in Alzheimer’s disease.

Her group combines conventional bio/histochemistry and state-of-the-art molecular imaging approaches, such as Spectral FRET and Fluorescence Lifetime Imaging Microscopy to monitor conformational changes of a single molecule or molecular complexes, and to untangle the chain of events leading to neurodegeneration. The main emphasis is on the conformational changes of presenilin1 (PS1)-secretase, and its interactions with a variety of proteins in intact and/or live cells.

Dr. Berezovska's lab recent discovery of activity-induced interactions between PS1 and synaptic proteins links together several factors implicated in AD pathogenesis: high calcium, synaptic dysfunction and local changes in amyloid beta generation (Kuzuya et al., 2016).

Targeting PS1-Syt1/Syn1 interactions may open avenue for developing novel therapeutic strategies focusing on the synapse (Zoltowska et al., 2017). Another focus of the research in the lab is on understanding molecular factors and events, such as post-translational modifications, that may lead to pathogenic conformational change in wild type PS1 similar to that of fAD PS1 mutants (Maesako et al., 2017), and search for modulators of the PS1/gamma-secretase activity.

In addition, we are interested in exploring an intriguing link between the PS1/gamma-secretase and a major glutamate transporter in the CNS, GLT-1 (EAAT2) that we have recently uncovered (Zoltowska et al., 2018). The ultimate goal of Dr. Oksana Berezovska's research is to discover new therapeutic targets and to develop new strategies to halt the disease progression.