Tsuneya Ikezu, MD, PhD 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): - 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
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Education: | University of Tokyo College of Arts and Sciences BS, Biological Sciences, 1987 University of Tokyo Faculty of Medicine MD, Medicine, 1991 University of Tokyo Graduate School of Medicine PhD, Clinical Pharmacology, 1997 | Professional Positions: | 2004- Associate Professor, Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE 1999- Deputy Director, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 1999-2004 Assistant Professor, Department of Pathology and Microbiology University of Nebraska Medical Center, Omaha, NE 1997-1999 Postdoctoral Fellow, Department of Neurosciences The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 1994-97 Postdoctoral Fellow, Department of Anesthesia Shriners Burns Institute, Massachusetts General Hospital Harvard Medical School 1992- Postdoctoral Fellow, Department of Immunology/Arthritis VA Medical Center, University of California, San Francisco | | Honors & Awards: | Honors and Awards: Individual National Research Service Award, National Institutes of Health,1998 Vada Kinsman Oldfield Alzheimer's Research Award, 2000 | |