Oksana Berezovska, PhD, uses novel fluorescence microscopy approaches, and conventional cell biology and biochemistry approaches to study molecular mechanisms of Alzheimer's Disease.

Research Investigator Profile

Oksana Berezovska, PhD

Oksana Berezovska, PhD

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

 

 

Research Description

Our research goal is to study the cellular and molecular mechanisms of Alzheimer's disease (AD) pathology. An increase in A beta 42/40 ratio has been implicated in AD pathogenesis. We focus on the analysis of gamma-secretase and APP interactions, and examine mechanisms by which various genetic and pharmacological factors modulate A beta production and/or regulate the precision of APP cleavage by gamma-secretase that leads to a change in A beta 42/40 ratio.

My 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.

To learn more, visit the Berezovska Lab.

Research interests Alzheimer's, Amyloid beta, presenilin/gamma-secretase, subcellular trafficking, A beta and synaptic dysfunction
Research techniques  Cellular and Molecular biology techniques, cell culture, biochemistry, histology, microscopy/imaging
Diseases studied Alzheimer's disease
Selected publications
  1. Berezovska O., Ramdya P., Wolfe M.S., Bacskai BJ., Hyman BT. (2003). APP associates with a Nicastrin dependent docking site on the PS1/-secretase complex in cells demonstrated by Fluorescence Lifetime Imaging. J. Neurosci., 23(11), 4560-4566.
  2. Lleo A, Berezovska O, Herl L, Raju S, Deng A, Frosch MP, Irizarry M, and Hyman BT (2004). "Nonsteroidal anti-inflammatory drugs (NSAIDs) lower Abeta42 and change presenilin 1 conformation in vitro and in vivo", Nature Med. 10 (10), 1065-1066.
  3. Berezovska O., Lleo A., Herl LD., Frosch MP, Stern EA., Bacskai BJ., and Hyman BT. (2005). “Familial Alzheimer’s Disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein”. J.Neurosci, 25(11), 3009-3017
  4. Kengo Uemura, Christina M Lill, Xuejing Li, Jessica A Peters, Alexander Ivanov, Zhanyun Fan, Bart DeStrooper, Brian J. Bacskai, Bradley T Hyman and Oksana Berezovska. (2009). Allosteric Modulation of PS1/-Secretase Conformation Correlates with Amyloid 42/40 Ratio. PlosOne, Nov 18;4(11):e7893 PMCID: PMC2773935
  5. Kengo Uemura, Katherine C. Farner, Tadafumi Hashimoto, Navine Nasser-Ghodsi, Michael S. Wolfe, Edward H. Koo, Bradley T. Hyman, and Oksana Berezovska. Substrate docking to -sectretase allows access of -secretase modulators to an allosteric site. (2010); Nature Communications, Nov;1(8):130. PMCID: PMC3060602
  6. Kengo Uemura, Phill Jones, Katherine C Farner, Navine Nasser-Ghodsi, Oksana Berezovska; “Reciprocal relationship between APP positioning relative to the membrane and PS1 conformation”. (2011); Mol. Neurodegeneration, Feb 10;6(1):15. PMCID: PMC3046905.
  7. Ohki Y, Higo T, Uemura K, Shimada N, Osawa S, Berezovska O, Yokoshima S, Fukuyama T, Tomita T, Iwatsubo T ”Phenylpiperidine-type γ-secretase modulators target the transmembrane domain 1 of presenilin 1”. EMBO J. 2011 Oct 14;30(23):4815-24. [PMC-in process]
  8. Guix FX, Wahle T, Vennekens K, Snellinx A, Chavez-Gutierrez L, Ill-Raga G, Ramos E, Guardia-Laguarta C, Lleó A, Arimon M, Berezovska O, Muñoz FJ, Dotti CG, De Strooper B. Modification of γ-secretase by nitrosative stress links neuronal aging to sporadic alzheimer's disease. (2012), EMBO Mol Med, Apr 10. doi: 10.1002/emmm.201200243. [Epub ahead of print].
NCBI PubMed link NCBI PubMed Publications and NCBI PubMed publications (aka Oksana Berezovskaya, PhD)
E-mail address berezovskaja@helix.mgh.harvard.edu
Lab mailing address MassGeneral Institute for Neurodegenerative Disease
114 16th Street, Room 2850
Charlestown, MA 02129

 

 

Updated 7/11/2012