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Andrea J. Tenner

Professor, Molecular Biology and Biochemistry
School of Biological Sciences

Professor, Pathology
School of Medicine

Professor, Neurobiology and Behavior
School of Biological Sciences

PH.D., University of California, San Diego, 1977

Phone: (949) 824-3268
Fax: (949) 824-8551
Email: atenner@uci.edu

University of California, Irvine
3205 McGaugh Hall
2228 McGaugh Hall
Mail Code: 3900
Irvine, CA 92697

picture of Andrea J. Tenner

Research
Interests
Innate Immunity; Inflammation; Complement; Alzheimer's Disease; Cell Surface Receptors; Phagocytosis
   
URLs darwin.bio.uci.edu/~faculty/tenner/
   
Tenner Lab Website
   
Academic
Distinctions
1994 AAAS Fellow
2005-06 UCI Emeritae/i Association Faculty Mentorship Award
   
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 mouse models of AD, we have evidence consistent with the hypothesis that complement activation and subsequent inflammatory events contribute to the pathogenesis of dementia in AD, and are currently testing candidate therapeutics to prevent or slow the progression of pathogenic events that lead to Alzheimer’s Disease in mouse models. In addition, we 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.
   
Publications Current publications from Pubmed
   
  Benoit, M.E., Hernandez, M., Dinh, M., Benavente,F., Vasquez,O. and Tenner, A.J. C1q-induced LRP1B and GPR6, expressed early in AD mouse models, are essential for the C1q-mediated protection against Aß neurotoxicity, J. Biol. Chem. 288:654-665 2013. PMC3537064
   
  Fonseca, M.I., McGuire, S.O., Counts,S.E. and Tenner, A.J., Complement Activation Fragment C5a Receptors, CD88 and C5L2, are associated with neurofibrillary pathology. J. Neuroinflammation 10:25, 2013. PMCID: PMC3605123
   
  Chandrasekhar, A., Dinasarapu,D.R., Tenner, A.J., Subramaniam, S., Complement C1q subcomponent subunit A, UCSD Molecule Page, 2012, doi:10.6072/H0.MP.A004228.01)
   
  Benoit, M.E., Clarke, E.V., Morgado, P., Fraser, D.A. and Tenner, A.J., Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells, J. Immunol 188 5682-5693, 2012.
   
  Linnartz B, Kopatz J, Tenner AJ, Neumann H., Sialic Acid on the neuronal glycocalyx prevents complement c1 binding and complement receptor-3-mediated removal by microglia.
J Neurosci. 32(3):946-52, 2012.
   
  Benoit ME, Tenner AJ., Complement protein C1q-mediated neuroprotection is correlated with regulation of neuronal gene and microRNA expression. J Neurosci. 2011 Mar 2;31(9):3459-69.
   
  Veerhuis R, Nielsen HM, Tenner AJ. Complement in the brain. Mol Immunol. 2011 Aug;48(14):1592-603.
   
  Fonseca MI, Chu SH, Berci AM, Benoit ME, Peters DG, Kimura Y, Tenner AJ., Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease. J Neuroinflammation. 2011 Jan 15;8(1):4.
   
  Fraser D.A., Tenner AJ., Innate immune proteins C1q and mannan-binding lectin enhance clearance of atherogenic lipoproteins by human monocytes and macrophages. J Immunol. 2010 Oct 1;185(7):3932-9.
   
  Fraser.D.A., Pisalyaput, K., and Tenner, A.J., C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production. J. Neurochem. 112:733-743, 2010.
   
  Ager, R.R., Fonseca, M.I., Chu,S., Sanderson, S., Taylor, S.M., Woodruff, T.M., and Tenner, A.J., Microglial C5aR (CD88) expression correlates with amyloid-ß deposition in murine models of Alzheimer’s Disease, J. Neurochem. 113:389–401, 2010.
   
  Klos, A., Tenner, A.J., Johswich, K-O., Ager, R.R., Reis, E.S. and J. Köhl, The Role of the Anaphylatoxins in Health and Disease. Mol. Immunol. 46:13624-13648, 2009.
   
  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.
   
  Fraser,D.A., Laust, A.K., Nelson, E.L. and Tenner, A.J., C1q differentially modulates phagocytosis and cytokine responses during ingestion of apoptotic cells by human monocytes, macrophages, and dendritic cells. J.Immunol. 183;6175-6185, 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.
   
  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.
   
  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.
   
  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.
   
  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.
   
  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.
   
  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.
   
  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.
   
Grants NIH NS35144 “Complement and Inflammatory Factors in AD Pathogenesis”
   
NIH NIA AG 00538 Program Project Grant - Project 4 Leader: Neuroprotection and neuroinflammation induced by the complement proteins C1q and C5a
   
Alzheimer's Association
   
Professional
Societies
American Association of Immunology
Society for Neuroscience
American Society for Cell Biology
International Complement Society, Founding Councilor
Society for Leukocyte Biology
American Society for Neurochemistry
American Society for Biochemistry and Molecular Biology
International Complement Society, President-Elect
   
Other Experience ADVANCE Equity Advisor
UCI 2004—2007

Graduate Programs Immunology and Pathogenesis

Biotechnology

Cellular and Molecular Biosciences

Interdepartmental Neuroscience Program

   
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 05/13/2013