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Katja Simon

Autophagy in the immune and hematopoietic system

Katja Simon is a Professor at the Kennedy Institute, Oxford University UK, studying cell fates in the hematopoietic system. She trained as an Immunologist under Avrion Mitchison at the Deutsche Rjheumforschungszentum Berlin and found that TH1 cytokines are found in excess in human autoimmune diseases in her PhD. As a postdoc at the Centre d’Immunologie Marseille Luminy, she investigated transcription factors regulating thymic cell death. During her second postdoc in Oxford she pursued her interest in cell fate, studying cell death molecules (Trail and FasL) in thymic selection, inflammation and tumour immunity. In 2007, as a principal investigator she set up an independent line of enquiry investigating autophagy, in the hematopoietic & immune system. Her group discovered that autophagy, the main conserved cellular bulk degradation pathway, maintains healthy red blood cells, stem cells and memory T cells, promotes differentiation and prevents ageing.


Project outline

Autophagy’s role in the formation or maintenance of memory T cells


Autophagy is a conserved pathway that delivers unwanted bulk cytoplasmic material to the lysosome. We have previously shown that the memory CD8+ T cell pool cannot form without autophagy [1]. Memory T cells are required for efficient vaccination. In the elderly it is well known that setting up a de novo response to vaccination is ineffective. Our data indicate that CD8+ T cells from elderly human or mice have low autophagy levels [2]. When we boost autophagy levels pharmacologically, the T cell memory response to influenza is restored in the elderly [1]. It is not clear whether autophagy is required for the maintenance or the formation/differentiation of memory T cells. In this project we will address both hypotheses while also elucidating the molecular mechanism.  Memory T cells are quiescent and long-lived and the maintenance of that lifestyle is thought to require autophagy, as our work in hematopoietic stem cells suggests [3]. In fact, rarely dividing cells have been proposed to have less opportunity to dilute damaged cytoplasmic material to their daughter cells, however, this has not been proven experimentally. On the other hand, we know that autophagy affects differentiation of various cell types including red blood cells and HSCs [4] [5], again, the mechanism remains largely unclear but may include a switch in metabolism. To address these questions we will use established and new in vivo models, and combine biochemical and “omics” approaches with high-resolution imaging and flow cytometry. Our lab is funded by a Wellcome Trust investigator award and includes 3 postdocs, 1 RA and 2 DPhil students. We have moved to the Kennedy Institute of Rheumatology (KIR) in 2016. The KIR recently re-settled in Oxford to a new building on the Churchill hospital site and is now under the directorship of Fiona Powrie with a research focus on inflammation.More than half of the faculty members have been recruited in the last yeas. Will use the KIR’s state-of-the-art facilities, and will continue to draw on other Oxford-based technologies as well as on the expertise of our local, national and international collaborators. For further information and enquiries, please contact Katja Simon Also consult the lab’s website

1.         Puleston, D.J., et al., Elife, 2014. 3.

2.         Phadwal, K., et al., Autophagy, 2012. 8(4).

3.         Mortensen, M., et al., J Exp Med, 2011. 208(3): p. 455-67.

4.         Mortensen, M., et al., Proc Natl Acad Sci U S A, 2010. 107(2): p. 832-7.

5.         Mizushima, N. and B. Levine, Nat Cell Biol, 2010. 12(9): p. 823-30.