Tsuneya Ikezu, MD, PhD

Professor and Vice chair for Research Director, Center for Neurodegenerative Disorders University of Nebraska Medical Center Center for Neurovirology and Neurodegenerative Disorders Durham Research Center II, 3066 University of Nebraska Medical Center 985930 Nebraska Medical Center Omaha, Nebraska, 68198-5930 Phone: (402) 559-9565 FAX: (402) 559-7495 tikezu@unmc.edu

Research Interests:

Research in the Laboratory of Molecular Neuroscience focuses on the therapeutic inventions on transgenic animal models of Alzheimer's disease (AD), including beta-amyloidosis and tauopathy, and regulation of HIV-1 innate immunity and neurotoxicity by host genes. We utilize adenovirus and adeno-associated virus (AAV) gene transfer of gene of our interest to protect neuronal and cognitive function of disease brain in the animal models. Standard biochemistry, neuropathology, and behavioral tests are employed for the characterization of gene-delivered mouse models.

We are also interested in the development of a new fluorescent compounds which bind to the beta-sheet structure of protein aggregates. These compounds can be utilized for imaging of protein aggregates in vitro or in vivo, and potential drug for inhibiting protein aggregation. HIV-associated neurological disorders (HAND) is an emerging epidemic disorders in elderly AIDS patients, and we are characterizing host genes involved in suppression of viral replication in infected cells (such as OTK18/ZNF175) and novel gene involved in protecting neurons from viral toxicity through genome-wide siRNA library screening of human genes in vitro.

Beta-amyloidosis in HAND is an emerging epidemic disorders in elderly AIDS patients. We are developing a new humanized mouse model for understanding the role of HIV infection and anti-retroviral drugs on the progression of beta-amyloidosis and insulin resistance.

Select Publications (last 3 years):

Kiyota T, Yamamoto M, Walsh SM, Martinez LB, Schroder B, Jacobsen MT, Swan R, Buescher JL, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, and Ikezu T. CCL2 accelerates microglia-mediated beta-amyloidosis and progression of Alzheimer-like disease. PLoS One 4:e6197 (2009)

Ikezu T. The aging of human-immunodeficiency-virus-associated neurocognitive disorders. J Neuroimmune Pharmacol 2009, 4:161-2 (Special Issue Guest Editor)

Kiyota T, Yamamoto M, Schroder B, Jacobsen MT, Swan RJ, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, and Ikezu T. AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice Mol Ther 2009; 17(5):803-9

Sato S, Xu J, Okuyama S, Martinez LB, Walsh SM, Jacobsen MT, Swan R, Schlautman JD, Ciborowski P, and Ikezu T. Spatial learning impairment, enhanced Cdk5/p35 activity, and down-regulation of NMDA receptor in transgenic mice expressing tau-tubulin kinase 1. J Neurosci 28:14511-21 (2008)

Xu J, Ikezu T. The comorbidity of HIV-associated neurocognitive disorders and Alzheimer's disease: a foreseeable medical challenge in post-HAART era. J Neuroimmune Pharmacol 4:200-12 (2008)

Martinez LB, Walsh SM, Jacobsen MT, Sato S, Wiederin J, Ciborowski P, and Ikezu T. Calpain and proteasomal regulation of antiretroviral zinc finger protein OTK18 in human macrophages: Visualization in live cells by intramolecular FRET. J Neuroimmune Pharmacol 4:116-28 (2008)

Buescher JL, Martinez LB, Sato S, Okuyama S, and Ikezu T. YY1 and FoxD3 regulate antiretroviral zinc finger protein OTK18 promoter activation induced by HIV-1 infection: Implications in brain perivascular macrophage-specific OTK18 gene expression. J Neuroimmune Pharmacol 4:103-15 (2008)

Yamamoto M, Kiyota T, Walsh SM, Liu J, Kipnis J, Ikezu T. Cytokine-mediated inhibition of fibrillar amyloid-b peptide degradation by human mononuclear phagocytes. J Immunol 181:3877-86 (2008)

Yamamoto M, Ramirez SH, Sato S, Kiyota T, Cerny RL, Kaibuchi K, Persidsky Y, and Ikezu T. Phosphorylation of Claudin-5 and Occludin by Rho Kinase in Brain Endothelial Cells. Am J Pathol 172:521-33 (2008)

Gorantla S, Lui J, Sneller H, Dou H, Smith L, Ikezu T, Holguin A, Volsky DJ, Poluektova L, and Gendelman HE. Glatiramer Acetate Immunization Modulates Glial Function and Protects Neurons in a Murine Model of HIV-1 Encephalitis. J Immunol 179:4345-56 (2007).

Flaherty DP, Walsh SM, Kiyota T, Dong Y, Ikezu T, Vennerstrom JL. Polyfluorinated Styrylbenzene a-Amyloid Plaque Binding Ligands. J Med Chem 50:4986-92 (2007).

Yamamoto M, Kiyota T, Horiba M, Buescher JL, Walsh SM, Gendelman HE, Ikezu T. Interferon-g and tumor necrosis factor-a regulate amyloid-b plaque deposition and b-secretase expression in Swedish mutant APP transgenic mice. Am J Pathol 170:680-92 (2007)

Persidsky Y, Heilman D, Haorah J, Zelivyanskaya M, Persidsky R, Weber GA, Shimokawa H, Kaibuchi K, Ikezu T. Rho-mediated regulation of tight junctions during monocyte migration across blood-brain barrier in HIV-1 encephalitis. Blood 107:4770-80 (2006)

Sato S, Cerny RL, Buescher JL, Ikezu T. Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation. J Neurochem 98:1573-84 (2006)

Huang Y, Erdmann N, Peng H, Herek S, Davis JS, Luo X, Ikezu T, Zheng J. TRAIL-mediated apoptosis in HIV-1-infected macrophages is dependent on the inhibition of Akt-1 phosphorylation. J Immunol 177:2304-13 (2006)