Explore This Lab

Overview

Dr. Kastanenka at her office
Ksenia 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. We strongly believe that these translational studies are important for getting effective therapies to patients.

Research Positions

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

Publications

Visit PubMed for the most complete and up-to-date list of publications.

Lee YF, Gerashchenko D, Timofeev I, Bacskai BJ, and Kastanenka KV. Slow wave sleep is a promising intervention target for Alzheimer’s disease. Frontiers in Neuroscience. 2020 June 30.

Kastanenka KV, Moreno-Bote R, De Pitta M, Perea G, Erso-Pichot A, Masgrau R, Poskanzer KE, and Galea A. A roadmap to integrate astrocytes into systems neuroscience. Glia. 2019 May 6.

Kastanenka KV, Calvo-Rodriguez M, Hou SS, Zhou H, Takeda S, Arbel-Ornath M, Lariviere A, Lee YF, Kim A, Hawkes JM, Logan R, Feng D, Chen X, Gomperts SN and Bacskai BJ. Frequency-dependent exacerbation of Alzheimer’s disease neuropathophysiology. Scientific Reports, 2019 June 20.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Kastanenka KV, Landmesser LT. Optogenetic-mediated increases 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.

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.

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.

Talks

Circuit dynamics in Alzheimer’s disease. (2020) Seminar Speaker at Emory University. Virtual talk.

Aducanumab: a cure in mind, a cure in sight. (2020) Virtual Symposium. Turning Points: From Healthy Cells and Systems to Neurological Disease States. Virtual talk.

Optogenetic entrainment of neuronal circuits during development and disease states. (2020) Case Western Reserve University Seminar Series. Virtual talk.

On the brink of a cure for Alzheimer’s disease. (2020) Sterling Drug Visiting Lecture. Boston University, MA.

Optogenetic entrainment of slow brain rhythms in Alzheimer’s mice. (2019) Optogenetic Technologies and Applications Conference. Society for Biological Engineering. Boston, MA.

Tapping the potential of herbal botanicals as treatment for Alzheimer’s disease. (2019) Abstract selected for nanosymposium at Society for Neuroscience Meeting, Chicago, IL.

Disruptions of sleep-dependent slow brain rhythms in Alzheimer’s disease. (2019) Seminar Speaker at Veterans Affairs, Harvard Medical School, Boston, MA.

Characterization of slow wave disruptions in Alzheimer’s disease. (2019) Seminar Speaker at Taub Institute, Columbia University, New York, NY.

Taming hyperexcitability with optogenetics in aging. (2019) Inhibition in the CNS. Newry, ME.

Overview of leading edge research in the field of Alzheimer’s disease. (2019) Alzheimer’s Association. A map through the maze. Worchester, MA.

Optogenetic control of neuronal circuits during development and disease states. (2019) Boston College, Newton, MA.

Tapping the potential of herbal botanicals for prevention and cure of Alzheimer’s disease. (2019) Alzheimer Unit presentation at Massachusetts General Hospital. Charlestown, MA.

Aberrant slow oscillations might link sleep disruptions to memory deficits in Alzheimer’s disease. (2019) Massachusetts General Hospital sleep journal club. Charlestown, MA.

Optogenetic manipulations of slow oscillations in an Alzheimer’s mouse model. (2019) Seminar speaker at Laval University and Cervo Brain Research Centre, Quebec City, Canada.

Aberrant circuit dynamics in an Alzheimer’s animal model. (2018) Cold Spring Harbor Meeting. Cold Spring Harbor, NY.

Neural circuit dynamics during development and disease. (2018) Keynote speaker for the 21st annual Loma Linda University basic science research symposium. Loma Linda, CA.

Conventional and unconventional approaches to therapy development for Alzheimer’s disease. (2018) Massachusetts General Hospital memory disorders unit and movement disorders unit conference. Boston, MA.

Increasing the frequency of slow cortical oscillations exacerbates the neuropathophysiology of Alzheimer’s disease. (2017) Abstract selected for nanosymposium at Society for Neuroscience Meeting, Washington, D.C.

Novel botanical drug DA-9803 prevents structural and functional deficits in Alzheimer’s mouse models. (2017) Alzheimer Unit presentation at Massachusetts General Hospital, Charlestown, MA.

Optogenetic restoration of disrupted slow oscillations halts amyloid deposition and restores calcium homeostasis in an animal model of Alzheimer’s disease. (2016) Abstract selected for nanosymposium at Society for Neuroscience Meeting, San Diego, CA.

Aducanumab targets high molecular weight soluble abeta oligomers and restores calcium to normal levels in Tg2576 mice. (2016) Alzheimer’s Association International Conference, Toronto, ON, Canada.

Renewed promise in immunotherapy as a potential cure for Alzheimer’s disease. (2015) MIND seminar at Massachusetts General Hospital (MGH), Charlestown, MA.

The effect of increasing the frequency of slow oscillations on the neurodegenerative phenotypes in AD animal model. (2015) Alzheimer Unit presentation at MGH, Charlestown, MA.

Optogenetic rescue of disrupted slow oscillations in APP/PS1 mice. (2014) Alzheimer Unit presentation at MGH, Charlestown, MA.

Hyperactivity mediated loss of slow oscillations in APP/PS1 mice. (2013), Alzheimer Unit presentation at MGH, Charlestown, MA.

Immunotherapy with BIIB037 restored calcium homeostasis in Tg2576 mice. (2013) Abstract selected for nanosymposium at Society for Neuroscience Meeting, San Diego, CA.

BIIB037 Project (BART): multiphoton imaging studies in Tg2576 mice. (2013) Alzheimer Unit presentation at MGH, Charlestown, MA.

BIIB037 immunotherapy clears plaques in a mouse model of Alzheimer’s disease. (2012) Biogen, Cambridge, MA.

Our Team

In addition to principal investigator Ksenia Kastanenka, PhD, our lab includes:

  • Qiuchen (Jack) Zhao
  • Moustafa Algamal
  • Yee Fun (Evelyn) Lee
  • Alyssa Russ
  • Megi Maci
  • Liane Obaid

Lab Alumni

  • Amanda Greco