Massachusetts General Hospital

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.

Principal Investigator

Oksana Berezovska, PhD

• Associate Professor of Neurology,
  Harvard Medical School
• Assistant in Neuroscience,
  Massachusetts General Hospital

Research Scientists

• Muriel Arimon, PhD - Post Doc Fellow
• Xuejing Li, MD, PhD - Post Doc Fellow

Research Assistants & Technicians

• Navine Nasser-Ghodsi, BS - Lab Technician
• Kate Farner, BS - Lab Technician

Read about and apply for residency, fellowship and observership programs at http://www.massgeneral.org/neurology/education/.

Apply for temporary positions (summer interns) through the Bulfinch Temporary Service Web site at http://www.massgeneral.org/careers/temporary.aspx. Search for all opportunities using ID# 2200484.

All applicants should register with the Mass General Careers Web site at http://www.massgeneral.org/careers/viewall.aspx. Request a list of current open positions at mghmind-jobs@partners.org.

Selected Publications

1. Ramdya P., J.Skoch, Bacskai BJ., Hyman BT, and Berezovska O. Activated Notch associates with a Presenilin1/gamma-secretase docking site. 2003, J.Neurochem, 87, 843-850.
2. Berezovska O., Ramdya P., Wolfe M.S., Bacskai BJ., Hyman BT. APP associates with a Nicastrin dependent docking site on the PS1/gamma-secretase complex in cells demonstrated by Fluorescence Lifetime Imaging. J. Neurosci., 2003, 23(11), 4560-4566.
3. Lleo A, Berezovska O, Herl L, Raju S, Deng A, Frosch MP, Irizarry M, and Hyman BT "Nonsteroidal anti-inflammatory drugs (NSAIDs) lower A beta 42 and change presenilin 1 conformation in vitro and in vivo" 2004, Nature Med. 10 (10), 1065-1066.
4. Berezovska O., Lleo A., Herl LD., Frosch MP., Stern EA., Bacskai BJ., and Hyman BT. Familial Alzheimer’s Disease presenilin 1 mutations cause alterations in the conformation of presenilin and intarections with amyloid precursor protein. 2005 J.Neurosci, 25(11), 3009-3017.
5. Lleo A., Waldron E, von Arnim CA, Herl L, Tangredi MM, Peltan ID, Strickland DK, Koo EH, Hyman BT, Pietrzik CU, and Berezovska O. "Low density lipoprotein receptor-related protein (LRP) interacts with presenilin 1 and is a competitive substrate of the amyloid precursor protein (APP) for gamma-secretase" J. Biol Chem. 2005, 280(29):27303-9.

NCBI PubMed link

NCBI PubMed Publications and NCBI PubMed Publications  (aka Oksana Berezovskaya, PhD)