Welcome to the Tenner Lab


Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, CA

Our Research Focus:

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.