Edan Foley, PhD

Dept. of Medical Microbiology & Immunology
University of Alberta
Faculty of Medicine & Dentistry
6-71 Heritage Medical Research Centre
T6G 2S2 Edmonton, AB
Canada
Ph : (780) 492-2303
Fx : (780) 492-7521
Em : efoley@ualberta.ca

Web: Foley lab home page

Positions:

• Associate Professor, Dept. of Medical Microbiology & Immunology
• Tier 2 Canada Research Chair in Innate Immunity
• Alberta Heritage Foundation for Medical Research Scholar
• Directing Member, Alberta Institute for Viral Immunology

 

Research:

Multicellular organisms counter microbial invaders with elaborate immune systems that drive potent defense strategies tailored to the ultimate destruction of a specific invader. The innate immune response constitutes the first line of antimicrobial defense and is the only recognizable immune system in greater than 99% of all existing animals. Innate immune defenses are triggered by detection systems that recognize microbial signature molecules and quickly activate the appropriate responses. The humble fruitfly Drosophila melanogaster is a Cadillac organism for investigations of innate immunity, as the fruitfly is readily amenable to genetic manipulations and reproduces key aspects of human innate immune responses. Researchers in my lab use cell and molecular biology tools and genetic techniques to decipher critical innate immune responses in Drosophila. We use these insights into the Drosophila immune system as a springboard to inspire subsequent studies in mammalian cell culture systems.

Fly

Our Drosophila research focuses on the Immune deficiency (IMD) pathway, an evolutionary conserved signal transduction pathway that drives potent immune responses against gram-negative bacterial pathogens. IMD responses proceed through the coordinate activation of JNK, NF-kB and caspase signaling modules and involve the active participation of phagocytic blood cells, the fat body (liver equivalent) and the gut. Efficient IMD responses are characterized by neutralization of the pathogen and termination of the immune signals. While the NF-kB arm of the IMD pathway has been extensively explored in cell culture, molecular and whole-animal assays, the regulatory networks that determine JNK inputs into IMD signaling remain unexplored. We generated a whole-genome fly RNAi library to fully explore the genetic interactions that underpin JNK involvement in the IMD pathway. In this survey, we uncovered a completely novel link between the Pvr/ERK pathway and the IMD pathway. Previous studies implicated Pvr/ERK signaling in cell proliferation and cell migration. Our studies indicate that Pvr/ERK also responds to infection by attenuating signal transduction through the IMD pathway. We are currently exploring Pvr/ERK regulation of immune responses in a number of cell culture and whole-animal assays.

Human

The recent advent of high-throughput RNAi technologies for mammalian cell culture assays opens entirely new opportunities for complex reverse genetic studies in model systems of immediate biomedical relevance. Through our association with the RNAi screening facility at the Alberta Institute for Viral Immunology, we are in a position to pursue complex RNAi studies in mammalian cell culture assays. We are particularly interested in the human Tumor Necrosis Factor (TNF) pathway, a critical cytokine response pathway with overt similarities to the fly IMD pathway. In the TNF pathway, unchecked engagement of the JNK or caspase modules results in cell death, while the NF-kB module drives a dominant pro-survival response. Deregulated interplay between the individual modules has serious pathological implications and errant TNF pathway responses have been implicated in numerous diseases. We are conducting genome-wide RNAi studies to identify critical regulators of TNF responses and characterizing such regulators in cell and molecular biology assays.

 

People:

• David Bond (Graduate student)
• Brittany Fraser (Technician)
• Silvia Guntermann (Graduate Student)
• Brendon Parsons (Graduate student)
• Anja Schindler (Graduate student)

 

 

Publications:

Click here for most recent publications

 

Selected Publications (2006 – 2009)

1. Schindler, A and Foley, E. A functional RNAi screen identifies hexokinase 1 as a modifier of type II apoptosis. Cell Signal. 2010 May 8 [Epub ahead of print]
2. Bond, D., and Foley, E. A quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling. PLoS Pathog. 2009 5(11): e1000655. doi:10.1371/journal.ppat.1000655.
3. Guntermann, S., Primrose, D., and Foley, E. Dnr1-Dependent Regulation of the Drosophila Immune Deficiency Signaling Pathway. Dev Comp Immunol. 2009 33(1): 127-134.
4. Bond, D*., Primrose, D*., and Foley, E. Quantitative Evaluation of Signaling Events in Drosophila S2 cells. (*authors contributed equally). Biological Procedures Online. 2008 4(10):20-8.
5. Primrose, D., Chaudhry, S., Johnson, G., Hrdlicka, A., Schindler, A., Tran, D., and Foley, E. Dnr1 Interacts with the Drosophila Initiator Caspases Dredd and Dronc. J Cell Sci. 2007 1;120(Pt 7):1189-99. Epub 2007 Mar 6.
6. Saleh, M.C., van Rij, R., Hekele, A., Gillis, A., Foley, E., O'Farrell, P.H. and Andino, R. The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing. Nat Cell Biol. 2006 8(8):793-802. Epub 2006 Jul 23. Faculty 1000 must read selection. Research Highlight article in Nature 442, 332-333 (2006). Editor’s Choice in Science 313, 892-893 (2006). Research Highlight article in Nature Reviews Mol. Cell. Biol. 7, 630 (2006).
7. Stroschein, S., Foley, E., O’Farrell, P.H., and Johnson, A.D. Identification of Drosophila gene products required for phagocytosis of Candida albicans. PLoS Biology. 2006 Jan;4(1):e4. Epub 2005 Dec 20. Faculty 1000 must read selection.