Tenner, Andrea J. - University of California, Irvine - Department of Molecular Biology and Biochemistry

个人简介

1994 AAAS Fellow 2005-06 UCI Emeritae/i Association Faculty Mentorship Award 2014-15 Daniel G. Aldrich, Jr. Distinguished University Service Award 2015 Society for Leukocyte Biology Honorary Life Member

研究领域

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. We have been elucidating mechanisms by which phagocytic cells regulate induction of an appropriate adaptive response. As phagocytic cells ingest distinct particles specific gene expression programs are initiated that influences th induction of an appropriate immune response. Thus, we are investigating the down stream events such as cytokine expression resulting from the interaction of pattern recognition signals 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 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. We use novel mouse models and cell isolation procedures to assess the molecular basis of these effects to identify targets for therapeutic intervention in neurodegenerative diseases.

近期论文

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Clarke, E.V., Weist, B.M., Walsh, C.M. and Tenner, A.J., Complement protein C1q bound to apoptotic cells suppresses human macrophage and dendritic-cell mediated Th17 and Th1 T cell subset proliferation. J. Leuk. Biol. 97:147-160, 2015. Clarke, E.V. and Tenner, A.J., Complement modulation of T cell immune responses during homeostasis and disease. J. Leuk. Biol. 96:745-756, 2014. 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.