NIH Training Grant Fellow: Elizabeth Clarke

Elizabeth Clarke

Elizabeth V. Clarke is a Ph.D. candidate in Andrea Tenner’s lab. Prior to beginning her doctoral studies, she acquired training in biophysical chemistry and structural biology (M.S.), epidemiology (M.P.H.) as well as drug development in the biotech industry. She therefore approaches her Ph.D. research with an interest in understanding human disease at the molecular level, the ultimate aim being the discovery of potential therapeutic targets.

The major goal of her Ph.D. thesis research is to understand the physiological role of complement protein C1q on T cell activation and macrophage signaling. Previous studies by the Tenner lab and others have highlighted a function for C1q in directing phagocytic and cytokine responses in primary human macrophages and other phagocytic cells.

She was involved in the discovery that when C1q is bound to apoptotic cells (AC), it directs macrophages ingesting these cells towards a more regulatory role during the immune response by stimulating production of the anti-inflammatory cytokines IL-27 and IL-10, decreasing secretion of pro-inflammatory cytokines and limiting inflammasome activation. She then found that these responses correlate with the phosphorylation of the transcription factor STAT1.

Her thesis project aims to define (a) the impact of C1q on macrophage-mediated T cell activation and (b) the macrophage signaling mechanisms occurring in response to C1q and whether these correlate with the observed cytokine responses, specifically during the clearance of apoptotic cells.

Collectively, these studies will further the understanding of the physiological role of C1q on human macrophage signaling and T cell activation. Given that C1q-deficient individuals present with systemic lupus erythematosus (SLE)-like disease and C1q knock-out mice can develop autoantibodies and SLE-like disease, knowledge of specific C1q-mediated events could lead to targeted therapeutics for these individuals.

The second project she is pursuing aims to define functional alterations in CR1 (complement receptor 1) SNPs associated with Alzheimer's Disease risk. Recent GWAS reports have identified SNPs at the CR1 locus associated with Alzheimer's Disease (AD) but the mechanistic explanation for these associations remains to be uncovered. In humans, CR1 influences the phagocytosis of C3b-and potentially C1q-opsonized particles by phagocytes, and clearance of immune complexes via erythocyte-mediated immune adherence and subsequent delivery to liver and spleen. A similar erythrocyte-CR1 clearance mechanism may also be involved in peripheral clearance of amyloid beta (Aβ) protein (a causative agent of AD). Specifically, the C3b-CR1 and/or C1q-CR1 interaction may be functionally altered in AD patients thereby altering Aβ clearance. Thus, she is evaluating whether CR1 protein containing these SNPs has altered binding to the opsonins C3b and C1q.


1. Selected oral presentation in a Block Symposium at IMMUNOLOGY 2013, the annual meeting of the American Association of Immunologists (AAI)

2. 2013 American Association of Immunologists (AAI) Trainee Abstract Award for the IMMUNOLOGY 2013 annual AAI meeting

3. First Prize Poster Award at the UC Irvine Institute for Immunology Fair 2012

4. UC Irvine Institute for Immunology Training Grant (2012-2013)

5. Lupus Foundation of American (LFA) 2012 Gina M. Finzi Memorial Student Summer Fellowship (5/2012 - 8/2012)

6. Society for Leukocyte Biology (SLB) Travel Award towards 2011 Annual Meeting (Kansas City, MO 9/2011)


Benoit, M.E., Clarke, E.V., Morgado, P., Fraser, D.A. & 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).