Andrea J. TennerProfessor, Molecular Biology and Biochemistry Professor, Pathology Professor, Neurobiology and Behavior Associate Dean for Research |
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Research Interests |
Innate Immunity; Inflammation; Complement; Alzheimer's Disease; Cell Surface Receptors; Phagocytosis | |
| URLs | darwin.bio.uci.edu/~faculty/tenner/ | |
| Tenner Lab Website | ||
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Academic Distinctions |
1994 AAAS Fellow 2005-06 UCI Emeritae/i Association Faculty Mentorship Award |
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Research Abstract |
The basic understanding of the immune system has undergone a substantial paradigm shift in the past decade as an awareness of the power and influence of the innate immune system has emerged. Essentially, it is now being recognized that the nature of the first response to invasion has significant influence in determining the nature of the subsequent adaptive immune response. That is, it is this first response that assesses the level of danger of a particular intrusion or injury and initiates a program of protection. My laboratory is focused on the role of specific elements of the innate immune system in host defense and in maintaining a balance of protective responses in the host. One major effort is in elucidating mechanisms by which phagocytic cells regulate induction of an appropriate adaptive response. Current projects focus on the intracellular signaling pathways that result as phagocytic cells ingest distinct particles and subsequent gene expression that influences the induction of an appropriate immune response. Thus, we are investigating the down stream events such as cytokine expression resulting from the interaction of defense collagens in the context of various particles targeted for ingestion. The second major research area is the investigation of the role of complement activation and subsequent inflammation in Alzheimer’s Disease. The neuropathological structures that are the hallmark of Alzheimer's disease (AD) include senile plaques composed of a proposed pathogenic peptide fragment, beta-amyloid (A-Beta), neurofibrillary tangles and loss of neurons. Using synthetic amyloid peptides and monitoring the macromolecular structure by circular dichroism and electron microscopy, we identified the specific regions of the beta-amyloid molecule that are involved in C1q binding and are necessary for complement activation. Using a mouse model of AD, we have evidence consistent with the hypothesis that complement activation and subsequent inflammatory events contribute to the pathogenesis of dementia in AD. Identification of the critical detrimental pathways should lead to effective treatments to prevent or slow the progression of pathogenic events that lead to Alzheimer’s Disease. In addition, we also postulate that C1q may be a response to injury that could play a protective role in the early stages of disease by enhancing the clearance of cellular debris, altering the effects of the amyloid peptide on microglia, and/or providing direct neuroprotective effects. Three models are used to test these hypotheses: in vitro isolated and mixed neuron and glia cultures, organotypic slice cultures and transgenic animals. Patents: "Host Defense Enhancement", Andrea J. Tenner and Ronald R. Nepomuceno, filed November 18, 1996, issued October 12, 1999. U.S. Patent # 5,965,439. |
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| Publications | Fonseca, M.F., Ager, R.R., Chu, S., Yazan, O., Sanderson, S., LaFerla, F.M., Taylor, S.M., Woodruff, T.M., Tenner, A.J., Treatment with a C5aR Antagonist Decreases Pathology and Enhances Behavioral Performance in Murine Models of Alzheimer Disease. J. Immunol. 183:1375-1383, 2009. | |
| Zhou, J., Fonseca,, M.I., Pisalyaput, K. and Tenner, A.J. Complement C3 and C4 expression in murine mouse models of Alzheimer’s Disease. J. Neurochem. 106: 2080-2092, 2008. | ||
| Li,M., Ager, R.R., Fraser, D.A., Tjokro, N.O. and Tenner, AJ., Development of a Humanized C1q A Chain Knock-in Mouse: Assessment of Antibody Independent ß-Amyloid Induced Complement Activation. Mol. Immunol. 45:3244-3252, 2008. | ||
| Lillis, A.P., Greenlee, M.C., Mikhailenko, I., Pizzo, S.V., Tenner, A.J., Strickland, D.K.and Bohlson, S.S. The low-density lipoprotein receptor-related protein (LRP/CD91) is not required for the C1q-triggered enhancement of phagocytosis in murine macrophages. J.Immunol. 181:364-373, 2008. | ||
| Fraser, D.A. and Tenner, A.J. Directing an appropriate immune response: The role of defense collagens and other soluble pattern recognition molecules. Current Drug Targets, "Modulators of the Innate Immune System." Suzanne S. Bohlson, guest editor; Bentham Science Publishers, 9:113-122, 2008. | ||
| Tenner, A.J. and Pisalyaput, K., The Complement System in the CNS: Thinking again. In Central Nervous System Diseases and Inflammation, Eds: Thomas E. Lane, Monica Carson, Connie Bergmann, Tony Wyss-Coray, Springer, New York (Invited Review), pp. 153-174, 2008. | ||
| Pisalyaput, K. and Tenner, A.J., Complement component C1q inhibits ß-amyloid and serum amyloid P induced neurotoxicity via caspase and calpain-independent mechanisms. J. Neurochem. 104:696-707, 2008. | ||
| Fraser, D.A., Arora, M., Bohlson, S.S., Lozano, E., and Tenner, A.J., Generation of Inhibitory NFkB complexes and pCREB correlates with the anti-inflammatory activity of complement protein C1q in human monocytes. J. Biol. Chem. 282:7360-7367, 2007 | ||
| Bohlson, S.S., Fraser, D.A., and Tenner, A.J. Complement Proteins C1q and MBL are Pattern Recognition Molecules that Signal Immediate and Long Term Protective Immune Functions. Mol. Immunol. 44:33-43, 2007. | ||
| Chong, Y.H., Shin, Y.J., Lee, E.O., Kayed, R., Glabe, C.G., and Tenner, A.J. ERK1/2 activation mediates oligomeric Aß-induced neurotoxicity via caspase-3 activation and Tau cleavage in rat organotypic hippocampal slice cultures. J. Biol. Chem.281:20315-20325, 2006. | ||
| Tenner, A.J. and Fonseca, M.I. The Double Edged Flower: Roles of Complement Protein C1q in Neurodegenerative Diseases, Book Chapter, Advances in Experimental Medicine and Biology, Lambris, J.D. (Ed.), Springer, Vol. 586: 153-176, 2006. | ||
| Fraser, D.A., Bohlson, S.S., Jasinskiene, N., Rawal, N., Palmerini, G., Ruiz, S., Rochford, R., and Tenner, A.J., C1q and MBL, components of the innate immune system, influence monocyte cytokine expression, J. Leuk. Biol. 80:107-116, 2006. | ||
| Zhou, J., M. I. Fonseca, R. Kayed, S. D. Webster, I. Hernandez, O.Yazan, D. H. Cribbs, C.G. Glabe, and A. J. Tenner, “Novel Aß peptide immunogens modulate plaque pathology and inflammation in a murine model of Alzheimer’s Disease”, J. Neuroinflammation 2:28, 2005. | ||
| Bohlson, S.S., Silva, R., Fonseca, M. and Tenner, A.J. CD93 is rapidly shed from the surface of human myeloid cells and the soluble form is detected in human plasma, J. Immunol.175:1239-1247, 2005. | ||
| Li,M., Pisalyaput, K., Galvan, M., and Tenner, A.J., MCSF and IFNg Trigger Distinct Mechanisms for Augmentation of Aß-Induced Microglia Mediated Neurotoxicity, J. Neurochem. 91:623-633, 2004. | ||
| Zhang, M., Bohlson, S. S., Dy, M., and Tenner, A.J. Modulated Interaction of ERM protein, Moesin, with CD93. Immunology, 115:63-73, 2005. | ||
| Fan, R. and Tenner, A.J. Differential regulation of Aß42-induced neuronal C1q synthesis and microglial activation. J. Neuroinflammation 2: 1-13, 2005 | ||
| Bohlson, S.S., Zhang, M., Ortiz, C.E. and Tenner, A.J. The adaptor protein GIPC interacts with CD93 via a class I PDZ binding domain and a highly charged juxtamembrane region of the CD93 cytoplasmic tail. J. Leuk. Biol. 77: 80-89, 2005. | ||
| Fonseca, M.I., Zhou, J., Botto, M., and Tenner, A.J. Absence of Complement protein C1q leads to less neuropathology in transgenic mouse models of AD. ,J. Neuroscience 24: 6457-6465, 2004. | ||
| Fan, R. and Tenner, A.J., Complement C1q expression induced by Aß in rat hippocampal organotypic slice cultures. Exp. Neurology 185:241-253, 2004. | ||
| Grants | NIH NS35144 “Complement and Inflammatory Factors in AD Pathogenesis” | |
| NIH AI41090 “Interaction of C1q on Phagocytic Cells” | ||
| NIH NIA AG 00538 Program Project Grant - Project 4 Leader: Neuroprotection and neuroinflammation induced by the complement proteins C1q and C5a | ||
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Professional Societies |
American Association of Immunology Society for Neuroscience American Society for Cell Biology International Complement Society, Founding Councilor Society for Leukocyte Biology, Councilor American Society for Neurochemistry American Society for Biochemistry and Molecular Biology |
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| Other Experience |
ADVANCE Equity Advisor UCI 2004—2007 |
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| Graduate Programs |
Immunology and Pathogenesis Biotechnology Cellular and Molecular Biosciences Interdepartmental Neuroscience Program |
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| Research Centers | UCI MIND - Institute for Memory Impairment and Neurological Disorders | |
| Institute for Immunology | ||
| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2679 | |
| Last updated | 07/14/2009 | |