Tsuneya Ikezu, MD, PhD

Associate Professor University of Nebraska Medical Center Center for Neurovirology and Neurodegenerative Disorders 985215 Nebraska Medical Center Omaha, NE 68198-5880 Phone - 402.559.9565 Fax - 402.559.3744 tikezu@unmc.edu

Research Interests:

Our research focuses on the molecular pathogenesis of Alzheimer's disease (AD) and HIV-associated dementia (HAD). The hypothesis being tested here is that chronic brain inflammatory reactions contribute to the progressive neurodegeneration often observed during AD. Such an idea is substantiated by a recent report that anti-inflammatory drugs slow the onset and progression of disease, including A b deposition. Neuron-microglial interaction is being studied in both animal models and primary culture systems.

Our laboratory is also involved in the molecular characterization of mononuclear phagocyte activation upon HIV-1 infection. We have recently characterized a novel transcriptional factor, OTK18, which is expressed in human macrophage upon HIV-1 infection and has anti-retroviral activity in vitro. We are investigating the molecular mechanism of the anti-retroviral effect of OTK18 as a transcriptional factor. These studies will lead to extension of our understanding of HIV-1 associated dementia and AD. Multiple experimental methods, including molecular biology, neurobiology, and immunology, are utilized for the investigation.

Select Publications (last 3 years):

1. Yamamoto M, Horiba M, Buescher JL, Huang DR, Gendelman HE, Ransohoff RM, and Ikezu T. Overexpression of monocyte chemotactic protein-1 (MCP)-1/CCL2 in _-amyloid precursor protein transgenic mice show accelerated diffuse b-amyloid deposition. Am J Pathol, in press (2005)
2. Carlson KA, Leisman G, Limoges J, Pohlman GD, Horiba M, Buescher JL, Gendelman HE, and Ikezu T. Molecular characterization of a novel anti-retroviral transcriptional factor, OTK18. J Immunol 172:381-391 (2004)
3. Carlson KA, Limoges J, Pohlman GD, Masliah E, Ikezu T, and Gendelman HE. OTK18: A novel macrophage transcriptional suppressive factor linked to HIV encephalitis. J Neuroimmunol, 150:186-198 (2004)
4. Xiong H, McCabe L, Castello JK, Anderson ER, Weber GA, Monagham D, and Ikezu T. Activation of NR1a/NR2B receptors by macrophage conditioned media stimulated with APP-processing products: Implications for Alzheimer’s disease. Neurobiol Aging 25:905-911 (2004)
5. Li X, Ikezu T, and Hexum TD. G Protein bg Subunits Mediate the NPY Enhancement of ATP-Stimulated InsP Formation in Bovine Chromaffin Cells. PEPTIDES 25:267-74 (2004)
6. Ikezu T, Luo X, Weber GA, Zhao J, McCabe L, Buescher JL, Ghorpade A, Zheng J, and Xiong H. Amyloid precursor protein-processing products affects mononuclear phagocytes activation: Differential function of sAPP and A_ for neurotoxicity. J Neurochem 85:925-934 (2003)
7. Luo X, Weber GA, Zheng J, Gendelman HE, and Ikezu T. C1q-calreticulin induced oxidative neurotoxicity: Relevance for the neuropathgenesis of Alzheimer’s disease. J Neuroimmunol, 135:62-71 (2003)
8. Li X, Zhang P, Drakulich DA, Shen M, Weber GA, Ikezu T, and Hexum TD. Infection of Bovine Adrenal Chromaffin Cells Using a Recombinant Adenovirus Expressing GFP. J Neurosci Methods 122:91-96 (2002)