Tsuneya Ikezu, M.D., Ph.D.

Ikezu1209_3 (3)
Professor of Pharmacology & Experimental Therapeutics and Neurology
Department of Pharmacology

M.D., University of Tokyo Faculty of Medicine
Ph.D., University of Tokyo Graduate School of Medicine

Laboratory: Laboratory of Molecular NeuroTherapeutics

2016_AAIC_Toronto_Tuesday_IMG_4623

Dr. Tsuneya Ikezu at the plenary lecture for Alzheimer’s Association’s Inge Grundke-Iqbal Award for Alzheimer’s Research

Research Interests:

Research Interests: The Laboratory of Molecular NeuroTherapeutics mainly focuses on neuroimmune cell-mediated regulations of neuronal function, neurogenesis, neuroinflammation, and neurodegeneration. In particular, we are interested in how the innate immune-related molecules in the central nervous system (CNS) influences the pathology and progression of select neurodegenerative disorders e.g. Alzheimer’s Disease, frontotemporal dementia and autism spectrum disorders.

The current studies include pharmacological means to suppress the propagation of tau protein mouse models. We have created adeno-associated virus-mediated expression of tau protein, which shows spread from neurons to neurons in microglia and exosome synthesis-dependent manner (Asai H, et al Nat Neurosci 2015). AV summary.

A second focus of our lab is the investigation of inflammation-related autism spectrum disorders. Maternal immune activation refers to the systemic infection during the first or second trimester of pregnancy. This is a major risk of autism spectrum disorders. We hypothesize that maternal immune activation develops chronic alternation in microglial homeostatic function, which results in neurodevelopmental abnormality and autism-like phenotypes in animal models.

We use multiple biological reagents and techniques for our studies: tissue culture of neurons, neural stem cells and microglia, custom AAV vectors, stereotaxic intracranial injection, immunohistochemistry, in situ hybridization, electrophysiology and animal behavior.

 

  1. Preliminary Study of Plasma Exosomal Tau as a Potential Biomarker for Chronic Traumatic Encephalopathy. Stern RA, Tripodis Y, Baugh CM, Fritts NG, Martin BM, Chaisson C, Cantu RC, Joyce JA, Shah S, Ikezu T, Zhang J, Gercel-Taylor C, Taylor DD. J Alzheimers Dis. 2016;51(4):1099-109. doi: 10.3233/JAD-151028.
  2. Impairment of PARK14-dependent Ca(2+) signalling is a novel determinant of Parkinson’s disease. Zhou Q, Yen A, Rymarczyk G, Asai H, Trengrove C, Aziz N, Kirber MT, Mostoslavsky G, Ikezu T, Wolozin B, Bolotina VM. Nat Commun. 2016 Jan 12;7:10332. doi: 10.1038/ncomms10332.
  3. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, Wolozin B, Butovsky O, Kügler S, Ikezu TNat Neurosci. 2015 Oct 5. doi: 10.1038/nn.4132.
  4. The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer’s disease. Varnum MM, Kiyota T, Ingraham KL, Ikezu S, Ikezu TNeurobiol Aging. 2015 Aug 1. pii: S0197-4580(15)00393-0. doi: 10.1016/j.neurobiolaging.2015.07.027.
  5. miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction. Woodbury ME, Freilich RW, Cheng CJ, Asai H, Ikezu S, Boucher JD, Slack F, Ikezu TJ Neurosci. 4790-14.2015. PubMed PMID: 26134658
  6. PLXNA4 is associated with Alzheimer disease and modulates tau phosphorylation. Jun G, Asai H, Zeldich E, Drapeau E, Chen C, Chung J, Park JH, Kim S, Haroutunian V, Foroud T, Kuwano R, Haines JL, Pericak-Vance MA, Schellenberg GD, Lunetta KL, Kim JW, Buxbaum JD, Mayeux R, Ikezu T, Abraham CR, Farrer LA. Ann Neurol. 2014 Sep;76(3):379-92. doi: 10.1002/ana.24219.
  7. Tau-tubulin kinase. Ikezu S, Ikezu TFront Mol Neurosci. 2014 Apr 28;7:33. doi: 10.3389/fnmol.2014.00033. eCollection 2014. Review. PubMed PMID: 24808823; PubMed Central PMCID: PMC4009424.
  8. The spectrum of disease in chronic traumatic encephalopathy. McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC. Brain. 2012 Dec 2.
  9. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain. Varnum MM, Ikezu TArch Immunol Ther Exp (Warsz). 2012 Aug;60(4):251-66. doi: 10.1007/s00005-012-0181-2. Epub 2012 Jun 19. Review.
  10. Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies. Vanderweyde T, Yu H, Varnum M, Liu-Yesucevitz L, Citro A, Ikezu T, Duff K, Wolozin B. J Neurosci. 2012 Jun 13;32(24):8270-83. doi: 10.1523/JNEUROSCI.1592-12.2012.
  11. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Goldstein LE, Fisher AM, Tagge CA, Zhang XL, Velisek L, Sullivan JA, Upreti C, Kracht JM, Ericsson M, Wojnarowicz MW, Goletiani CJ, Maglakelidze GM, Casey N, Moncaster JA, Minaeva O, Moir RD, Nowinski CJ, Stern RA, Cantu RC, Geiling J, Blusztajn JK, Wolozin BL, Ikezu T, Stein TD, Budson AE, Kowall NW, Chargin D, Sharon A, Saman S, Hall GF, Moss WC, Cleveland RO, Tanzi RE, Stanton PK, McKee AC. Sci Transl Med. 2012 May 16;4(134):134ra60. doi: 10.1126/scitranslmed.3003716.
  12. FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer’s disease and has therapeutic implications for neurocognitive disorders. Kiyota T, Ingraham KL, Jacobsen MT, Xiong H, Ikezu TProc Natl Acad Sci U S A. 2011 Dec 6;108(49):E1339-48. doi: 10.1073/pnas.1102349108. Epub 2011 Oct 31.
  13. The spectrum of disease in chronic traumatic encephalopathy. McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC. Brain. 2012 Dec 2.
  14.  The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain. Varnum MM, Ikezu T. Arch Immunol Ther Exp (Warsz). 2012 Aug;60(4):251-66. doi: 10.1007/s00005-012-0181-2. Epub 2012 Jun 19. Review.
  15. Characterization of insulin degrading enzyme and other amyloid-β degrading proteases in human serum: a role in Alzheimer’s disease? Liu Z, Zhu H, Fang GG, Walsh K, Mwamburi M, Wolozin B, Abdul-Hay SO, Ikezu T, Leissring MA, Qiu WQ. J Alzheimers Dis. 2012;29(2):329-40. doi: 10.3233/JAD-2011-111472.
  16. AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. Kiyota T, Ingraham KL, Swan RJ, Jacobsen MT, Andrews SJ, Ikezu T. Gene Ther. 2012 Jul;19(7):724-33. doi: 10.1038/gt.2011.126. Epub 2011 Sep 15.
  17. CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer’s disease-like pathogenesis in APP+PS1 bigenic mice. Kiyota T, Okuyama S, Swan RJ, Jacobsen MT, Gendelman HE, Ikezu T. FASEB J. 2010 Aug;24(8):3093-102. doi: 10.1096/fj.10-155317. Epub 2010 Apr 6.
  18. Tau-tubulin kinase 1 enhances prefibrillar tau aggregation and motor neuron degeneration in P301L FTDP-17 tau-mutant mice. Xu J, Sato S, Okuyama S, Swan RJ, Jacobsen MT, Strunk E, Ikezu T. FASEB J. 2010 Aug;24(8):2904-15. doi: 10.1096/fj.09-150144. Epub 2010 Mar 30.
  19.  Real-time imaging and quantification of amyloid-beta peptide aggregates by novel quantum-dot nanoprobes. Tokuraku K, Marquardt M, Ikezu T. PLoS One. 2009 Dec 30;4(12):e8492. doi: 10.1371/journal.pone.0008492.

Office: 72 East Concord St.,L-606B
Email: tikezu@bu.edu
Phone: 617-414-2658
Fax: 617-638-4329