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The William Harvey Research Institute - Barts and The London

Dr Ezra Aksoy

Ezra

Early Careers Fellow - Lecturer

Centre: Biochemical Pharmacology

Email: e.aksoy@qmul.ac.uk
Telephone: +44(0) 20 7882 5920

Profile

I obtained my BSc degree in Microbiology at the Kansas State University, USA. After brief research experience at the Dana Farber Cancer Institute, I moved to Belgium where I carried out my doctoral studies at the Université Libre de Bruxelles, School of Medicine. During my PhD, I was fascinated by cell signalling networks and have studied the role of phosphoinositide 3 -kinase (PI3K) and PKC signalling downstream of Toll-like receptors (TLRs), an important member of the pattern recognition receptor (PRR) family. EMBO Long-term Fellowship and Marie Curie Intra-European Fellowship gave me the opportunity to carry out my post-doctoral research with Prof. Bart Vanhaesebroeck at Barts Cancer Institute, QMUL. During this period, I have demonstrated the importance of p110δ PI3K isoform mediated PI metabolism in coordinating TLR4 trafficking from the plasma membrane to the endosomes. In 2013, I was appointed as an Early Careers Fellow-Lecturer to start the “Mucosal Immunity and Signalling” group.

Research

Group members

Postdoctoral assistant: Dr. Raffaele Simeoli
Research assistant: Ms. Laura Medrano
BMedSci: Ms. Anusha Shanmuganathan

Interested postdoctoral candidates should contact me with a cover letter, CV and two letters of references.  Please contact me if you are a student and interested in rotating in the lab.

Summary 

My group is currently investigating the role of phosphatidylinositol lipids and their key enzymes, PI3Ks in vesicular trafficking processes (i.e. phagocytosis, endocytosis and autophagy) following activation of innate PRRs in health and disease states.

Phosphoinositol lipid metabolism in innate immunity and inflammation
Upon cellular activation, PI3Ks and PLCs induce acute changes in biological membranes. They generate lipid second messengers that control key cellular processes of vesicular traffic, secretion, differentiation and migration. PI3K family consists of three classes (I, II and III) and is evolutionarily conserved from soil-dwelling amoeba up to mammals. They are important regulators of host immunity and are often deregulated in inflammatory and metabolic diseases such as arthritis and cancer. To date, partial loss or mutation of Age1, the C. elegans orthologue of class I PI3K, results in enhanced immunity of worms due to superior bacterial clearance, which also impacts their longevity. Analogous to the observations in C. elegans, we postulated that the regulation of PI metabolism by PI3Ks endows fitness to the mammalian host, by topological control of immune signalling downstream of TLR4 and detoxifying endotoxin from the extracellular space. Similar homeostatic mechanism might be operative in signalling pathways in PRRs.

The role phosphoinositol metabolism in mucosal immunity, inflammation and regeneration
The intestinal mucosa can be considered as a large immunologic organ, lined up with trillions of microbes and plays a major role in the development of oral tolerance and host-defence. Our studies are aimed to understand how phosphatidylinositol signalling by Nod-like receptors and TLRs control innate immunity and translate these signals during host-microbial interplay in the gastrointestinal tract. By employing mouse genetics, we investigate how a single or a set of genes can shape mucosal landscape to the signals derived from the environment (e.g. microbes, particles, toxins) and impact on gut inflammation (inflammatory bowel disease -IBD), oral tolerance and regeneration.

Key Publications

For a full list of publications click here

  • Aksoy E, Salma Taboubi, Torres D, Delbauve S, Hachani A, maria A. Whitehead, Pearce WP, Berenjeno IM, Gemma Nock, Filloux A, Beyaert R, Flamand V and Vanhaesebroeck B. The p110delta isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock. Nature immunology 2012;13:1045-1054. (co-corresponding author).
  • Langlet C, Springael C, Johnson J, Thomas S, Flamand V, Leitges M, Goldman M, and Willems F,Aksoy E. PKCα controls MyD88-dependent TLR/IL-1R signaling and cytokine production in mouse and human dendritic cells. Eur J Immunol. 2010;40:505-15. (co-senior author).
  • Johnson, J., V. Albarani, Nguyen, M. Goldman, F. Willems, and Aksoy E. Protein kinase Cα is involved in interferon regulatory factor-3 activation and type I interferon-beta synthesis. J Biol Chem 2007; 282:15022-15032. (co-senior author).
  • Aksoy E., V. Albarani, M. Nguyen, J.F. Laes, J.L. Ruelle, D. De Wit, F. Willems, M. Goldman, and Goriely S. 2007. Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells. Blood 2007; 109:2887-2893.
  • Aksoy E., Vanden Berghe W, Detienne S, Amraoui Z, Fitzgerald KA, Haegeman G, Goldman M, and Willems F. Inhibition of phosphoinositide 3-kinase enhances TRIF-dependent NF-kappa B activation and IFN-beta synthesis downstream of Toll-like receptor 3 and 4. Eur J Immunol 2005;35:2200-2209.
  • Aksoy E., Zouain CZ, Vanhoutte F, Fontaine J, Pavelka N, Thieblemont N, Willems F, Ricciardi-Castagnoli P, Goldman M, Capron M, Ryffel B, and Trottein F. Double-stranded RNAs from the helminth parasite Schistosoma activate TLR3 in dendritic cells. J Biol Chem 2005;280:277-283.

Collaborators

Internal: Prof. Tom MacDonald (Blizard), Dr. Oliver Haworth (WHRI), Prof. John Gribben (BCI)

Local: Dr. Bart Vanhaesebroeck (UCL, London), Dr. Paul Brogan (UCL), Dr. Siobhan Burns (UCL), Dr. Klaus Okkenhaug (Babraham Institute, Cambridge), Dr. Jeffrey Barett (Wellcome Thrust Sanger Institute, Oxford), Dr. Sheena Cruickshank (Uni. of Manchester)

International: Dr. Rudi Beyaert (University of Gent, Belgium), Dr. Veronique Flamand (IMI, Free University of Brussels, Belgium)