multiphoton image of Alzheimer’s brain

Ksenia V. Kastanenka, PhD

Ksenia Kastanenka’s research interests lie in the sphere of aging with particular emphasis on Alzheimer’s disease. The laboratory is focused on studying circuitry disruption during the disease progression and mechanisms of action of Alzheimer’s therapeutics aimed at reversing the disease.

Overview

Ksenia V. Kastanenka, PhD

Alzheimer’s disease has traditionally been viewed as a proteinopathy. However, recent evidence highlights circuit disruptions as part of the disease progression. We implement optogenetics to control activity within neuronal circuits and imaging with multiphoton microscopy to monitor circuit dynamics with the aim to dissect the role neural activity plays in onset and development of Alzheimer’s disease.

In an attempt to prevent and/or reverse the disorder, we have partnered with industry leaders to study the effects and mechanisms of action of Alzheimer’s therapeutics, such as anti-Abeta immunotherapy, aducanumab, and the novel multimodal botanical extract DA-9803. We strongly believe that these translational studies are important for getting effective therapies to patients.

Publications

  1. György B, Lööv C, Zaborowski MP, Takeda S, Kleinstiver BP, Commins C, Kastanenka K, Mu D, Volak A, Giedraitis V, Lannfelt L, Maguire CA, Joung JK, Hyman BT, Breakefield XO, Ingelsson M. CRISPR/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer's Disease. Mol Ther Nucleic Acids. 2018 Jun 01; 11:429-440. PMID: 29858078.
  2. Wang X, Kastanenka KV, Arbel-Ornath M, Commins C, Kuzuya A, Lariviere AJ, Krafft GA, Hefti F, Jerecic J, Bacskai BJ. An acute functional screen identifies an effective antibody targeting amyloid-ß oligomers based on calcium imaging. Sci Rep. 2018 Mar 15; 8(1):4634. PMID: 29545579.
  3. Pagnier GJ, Kastanenka KV, Sohn M, Choi S, Choi SH, Soh H, Bacskai BJ. Novel botanical drug DA-9803 prevents deficits in Alzheimer's mouse models. Alzheimers Res Ther. 2018 Jan 29; 10(1):11. PMID: 29378621.
  4. Maesako M, Horlacher J, Zoltowska KM, Kastanenka KV, Kara E, Svirsky S, Keller LJ, Li X, Hyman BT, Bacskai BJ, Berezovska O. Pathogenic PS1 phosphorylation at Ser367. Elife. 2017 01 30; 6. PMID: 28132667.
  5. Kastanenka KV, Hou SS, Shakerdge N, Logan R, Feng D, Wegmann S, Chopra V, Hawkes JM, Chen X, Bacskai BJ. Optogenetic Restoration of Disrupted Slow Oscillations Halts Amyloid Deposition and Restores Calcium Homeostasis in an Animal Model of Alzheimer's Disease. PLoS One. 2017; 12(1):e0170275. PMID: 28114405.
  6. Kastanenka KV, Herlitze S, Boyden ES, Tsai L-H and Bacskai BJ. EC Neurology. Optogenetics shed light on Alzheimer’s disease. 2017; (01):27-29.
  7. Kastanenka KV, Bussiere T, Shakerdge N, Qian F, Weinreb PH, Rhodes K, Bacskai BJ. Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice. J Neurosci. 2016 12 14; 36(50):12549-12558. PMID: 27810931.
  8. Dumurgier J, Schraen S, Gabelle A, Vercruysse O, Bombois S, Laplanche JL, Peoc'h K, Sablonnière B, Kastanenka KV, Delaby C, Pasquier F, Touchon J, Hugon J, Paquet C, Lehmann S. Cerebrospinal fluid amyloid-ß 42/40 ratio in clinical setting of memory centers: a multicentric study. Alzheimers Res Ther. 2015; 7(1):30. PMID: 26034513; PMCID: PMC4450486.
  9. Kastanenka KV, Arbel-Ornath M, Hudry E, Galea E, Xie H, and Bacskai BJ. . Optical probes for in-vivo imaging. Optical Probes in Biology. Jin Zhang and Carsten Schultz (Eds). Taylor and Francis Group. USA. 2015.
  10. Wang X, Arbel-Ornath M, Wegmann SK, Kastanenka KV, and Bacskai BJ. Chapter 3: In vivo imaging in neurodegenerative diseases. Advances in intravital microscopy: from basic to clinical research. R. Weigert (Ed.), Springer. USA. 2014.
  11. Kastanenka KV, Landmesser LT. Optogenetic-mediated increases in in vivo spontaneous activity disrupt pool-specific but not dorsal-ventral motoneuron pathfinding. Proc Natl Acad Sci U S A. 2013 Oct 22; 110(43):17528-33. PMID: 24101487; PMCID: PMC3808638.
  12. Maeno-Hikichi Y, Polo-Parada L, Kastanenka KV, Landmesser LT. Frequency-dependent modes of synaptic vesicle endocytosis and exocytosis at adult mouse neuromuscular junctions. J Neurosci. 2011 Jan 19; 31(3):1093-105. PMID: 21248134; PMCID: PMC3642848.
  13. Kastanenka KV, Landmesser LT. In vivo activation of channelrhodopsin-2 reveals that normal patterns of spontaneous activity are required for motoneuron guidance and maintenance of guidance molecules. J Neurosci. 2010 Aug 04; 30(31):10575-85. PMID: 20686000; PMCID: PMC2934783.

Open Positions

Pre-doctoral, post-doctoral opportunities are currently available. Also, technician positions are open. Please contact kkastanenka@mgh.harvard.edu for more information.

Contact

Ksenia V. Kastanenka, PhD
Massachusetts General Hospital
Harvard Medical School
114 Sixteenth St., Rm 2900
Charlestown, MA 02129
USA

Email: kkastanenka@mgh.harvard.edu

 

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