Kastanenka Lab: Ksenia V. Kastanenka, PhD

Overview

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.

Algamal M, Russ AN, Miller MR, Hou SS, Maci M, Munting LP, Zhao Q, Gerashchenko D, Bacskai BJ, Kastanenka KV. Reduced excitatory neuron activity and interneuron-type-specific deficits in a mouse model of Alzheimer’s disease. Communications Biology. 2022 Dec 2.

Thankachan S, Yang C, Kastanenka KV, Bacskai BJ, Gerashchenko D. Low frequency visual stimulation enhances slow wave activity without disrupting the sleep pattern in mice. Sci Rep. 2022 Jul 19;12(1):12278.

Thankachan S, Gerashchenko A, Kastanenka KV, Bacskai BJ, Gerashchenko D. Optimization of real-time analysis of sleep-wake cycle in mice. MethodsX. 2022 Aug 8;9:101811.  

Lee YF, Lariviere A, Russ AN, Choi S-Z, Bacskai BJ, and Kastanenka KV.  Novel botanical therapeutic NB-02 effectively treats Alzheimer’s neuropathophysiology in an APP/PS1 mouse model. eNeuro. 29 April 2021, 8 (3) ENEURO.0389-20.2021; doi: https://doi.org/10.1523/ENEURO.0389-20.2021

Escartin C, Galea E, Lakatos A, O’Callaghan JP, Petzold GC, Serrano-Pozo A, Steinhauser C, Volterra A, Carmignoto G, Agarwal A, Allen NJ, Araque A, Barbeito L, Barzilai A, Bergles DE, Bonvento G, Butt AM, Chen WT, Cohen-Salmon M, Cunningham C, Deneen B, De Strooper B, Díaz-Castro B, Farina C, Freeman M, Gallo V, Goldman JE, Goldman SA, Götz M, Gutiérrez A, Haydon PG, Heiland DH, Hol EM, Holt MG, Iino M, Kastanenka KV, Kettenmann H, Khakh BS, Koizumi S, Lee CJ, Liddelow SA, MacVicar BA, Magistretti P, Messing A, Mishra A, Molofsky AV, Murai K, Norris CM, Okada S, Oliet SHR, Oliveira JF, Panatier A, Parpura V, Pekna M, Pekny M, Pellerin L, Perea G, Pérez-Nievas BG, Pfrieger FW, Poskanzer KA, Quintana FJ, Ransohoff RM, Riquelme-Perez M, Robel S, Rose CR, Rothstein J, Rouach N, Rowitch DH, Semyanov A, Sirko S, Sontheimer H, Swanson RA, Vitorica J, Wanner IB, Wood LB, Wu J, Zheng B, Zimmer ER, Zorec R, Sofroniew MV, Verkhratsky A. Reactive astrocyte nomenclature, definitions, and future directions. Nature Neuroscience. 2021 March 24 (3): 312-325. doi: 10.1038/s41593-020-00783-4

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. doi: 10.3389/fnins.2020.00705

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. doi: 10.1002/glia.23632

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. doi: 10.1038/s41598-019-44964-z.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Talks

R01: Elucidating circuit disruptions in Alzheimer’s disease. (2022) Neurology Retreat at Massachusetts General Hospital, Boston, MA. Talk.

The importance of mentors for postdoctoral fellows. (2022) Postdoctoral Retreat at Massachusetts General Hospital, Boston, MA. Talk.

Alzheimer’s disease: use of optogenetic approaches to understand circuit dysfunction. (2022) University of Missouri. Virtual seminar talk.

Targeting GABAertic interneurons to slow Alzheimer’s progression in APP/PS1 mice. (2022) Wesleyan University. Seminar talk.

Optogenetic and immunotherapy approaches to slow Alzheimer’s progression. (2022) Rush University. Grant Rounds. Virtual talk.

Optogenetic rescue of aberrant astrocytic activity slows Alzheimer’s progression. (2022) Northern Ohio Medical University. Virtual seminar.

How non-neuronal cells contribute to Alzheimer’s disease. (2022) BrightFocus Gala. Washington D.C. Talk

Optogenetic targeting of distinct cell types to slow Alzheimer’s disease. (2022) MGH Memory Disorders Unit & Movement Disorders Unit Conferences. Virtual seminar.

Astrocyte targeting with optogenetics slows Alzheimer’s disease in a mouse model. (2022) FastTrack at BrightFocus Foundation. San Diego, CA. Talk.

Targeting aberrant circuit activity in Alzheimer’s disease mouse models. (2022) Johns Hopkins University. Virtual talk.

Applying optogenetics to studies of Alzheimer’s disease. (2022) Neurophotonics Center Symposium. Boston University, MA. Virtual talk.

Optogenetic approaches targeting the tripartite synapse in Alzheimer’s disease. (2021) University of Minnesota, Virtual talk.

The role of astrocytes in Alzheimer’s disease. (2021) Fast Track at BrightFocus Foundation. Virtual talk.

Therapeutic targeting of circuit dysfunction in Alzheimer’s disease. (2021) Grand rounds at Washington University at St. Louis. Virtual talk.

Determining whether GT-002 restores slow oscillations in APP/PS1 mice. (2021) Virtual talk at Gabather.

Therapeutic treatment with NB-02 is effective at slowing Alzheimer’s progression in a mouse model. (2021) Virtual symposium Innovative Molecular, Physiological and Therapeutic Approaches to Neurodegenerative Disease. Virtual talk.

Rhythms of the brain affected by Alzheimer’s disease. (2021) Seminar at Brown University. Virtual talk.

Targeting brain rhythms to slow Alzheimer’s disease. (2021) Seminar at Beth Israel Medical Deaconess Center, Boston. Virtual talk.

Disruptions in sleep-dependent brain rhythms contribute to Alzheimer’s progression. (2021) Symposium speaker at University of Florida. Virtual talk.

Novel botanical therapeutic NB-02 prevents and slows Alzheimer’s progression. (2020) Seminar Speaker at University of Kentucky. Virtual talk.

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 21^st 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
• Morgan Miller
• Stephen Perle
• Shinya Yokomizo
• Lu Yu
• Sema Aygar
• Tri Doan
• Md. Joynal (Faruky) Abedin

Lab Alumni

• Moustafa Algamal

• Ryan Castro 
• Pariss D'Spain
• Shenyece Ferguson 
• Amanda Greco
• Lavender Lariviere 

• Yee Fun (Evelyn) Lee

• Megi Maci

• Liane Obaid
• Guillaume Pagnier 
• Alyssa Russ
• Naomi Shakerdge

• Esther Yu