Tomomi Kiyota, PhD

TOMOMI KIYOTA, PhD
Instructor

Laboratory of Howard E. Gendelman, MD

Phone: 402-559-8965
e-mail:  tkiyota@unmc.edu

Research Interests:
Invention of new therapeutic strategies for AD.

• My research mainly focuses on AAV-mediated gene delivery of inflammatory-signaling molecules and receptors in the brain to ameliorate the neuroinflammatory response by reactive astrocytes and microglia, enhance neurogenesis/ synaptic plasticity, and protect neuronal cell loss using mouse models of AD. Currently I am investigating roles of CD74 and dominant-negative forms of TNFRsf21 as blockers against beta-amyloidosis.

• My second focus is to investigate the role of the self-assembled catalase/PEI-PEG complex (nanozyme) as a new antioxidant to treat AD. This cutting-edge material is applied to mouse models of AD using a macrophage-based cell delivery system.

Long term goals:
The ultimate long-term goals of my research are: 1. To identify critical factors responsible for disease initiation and progression, and 2. To invent effectual therapeutic strategies to treat neurodegenerative disorders including, but not limited to, AD and Parkinson’s disease. This translational research component is critical to help improve the quality of life of both patients suffering from these diseases and the general population.

Representative Publications:

Kiyota T, Ingraham KL, Jacobsen MT, Xiong H, Ikezu T. FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer"s disease and has therapeutic implications for neurocognitive disorder. Proc Natl Acad Sci USA, 2011

Kiyota T, Ingraham KL, Swan RJ, Jacobsen MT, Andrews SJ, Ikezu T. AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. Gene Ther. 2011 Sept 15 doi: 10.1038/gt.2011.126

Lan X, Xu J, Kiyota T, Peng H, Zheng JC, Ikezu T. HIV-1 Reduces A{beta}-Degrading Enzymatic Activities in Primary Human Mononuclear Phagocytes. J Immunol. 2011 Jun 15;186(12):6925-32 

Flaherty DP, Kiyota T, Dong Y, Ikezu T, Vennerstrom JL. (2010) Phenolic bis-styrylbenzenes as β-amyloid binding ligands and free radical scavengers. J. Med Chem 25;53(22):7992-9.

Kiyota T, Okuyama S, Swan RJ, Jacobsen MT, Gendelman HE, Ikezu T (2010) CNS expression of anti-Inflammatory cytokine interleukin-4 attenuates Alzheimer’s disease-like pathogenesis in APP+PS1 bigenic mice. FASEB J. 24(8): 3093-1

Kiyota T, Yamamoto M, Xiong H, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, Ikezu T (2009) CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of neurocognitive dysfunction. PLoS ONE 4(7): e6197

Kiyota T, Yamamoto M, Schroder B, Jacobsen MT, Swan RJ, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, Ikezu T (2009) AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Mol. Ther. 17(5): 803-9. PMCID: PMC2709991

Yamamoto M*, Kiyota T*, Walsh SM, Liu J, Kipnis J, Ikezu T (2008) Cytokine-mediated inhibition of fibrillar amyloid-beta peptide degradation by human mononuclear phagocytes. J. Immunol. 181(6): 3877-3886  *Equal contribution PMCID: PMC2603577

Yamamoto M, Kiyota T, Walsh SM, Ikezu T (2007) Kinetic analysis of aggregated amyloid-beta peptide clearance in adult bone-marrow-derived macrophages from APP and CCL2 transgenic mice. J. Neuroimmune Pharmacol. 2(2): 213-221 

Yamamoto M, Kiyota T, Horiba M, Buescher JL, Walsh SM, Gendelman HE, Ikezu T (2007) Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice. Am. J. Pathol. 170(2): 680-92. PMCID: PMC1851864

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