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Simon group autophagy in the immune system

Autophagy is a major degradation pathway in the cell. While the ubiquitin/proteasome system degrades proteins, autophagy is thought to degrade bulk cytoplasmic material.

In fact, autophagosomes have been shown to engulf whole organelles, such as mitochondria, lipid droplets and Golgi for example, and consequently autophagy impacts on metabolism, apoptosis, differentiation, cell cycle and cell fate decisions in general.

Over the last 8 years we have studied the role of autophagy in the development and function of hematopoietic and immune cells using in vivo models and in vitro techniques applied to human samples.

We pioneered a technique detecting autophagy in primary cells and showed a decrease in autophagy levels in ageing T lymphocytes (Phadwal et al, Autophagy 2012). Our previous research also reveals that red blood cells need autophagy to degrade mitochondria for their final maturation (Mortensen et al, PNAS 2010).

Hematopoietic stem cells require autophagy for their maintenance (Mortensen, J Exp Med et al, 2011), and in the absence of autophagy, we observe a mild pre-leukemic phenotype. We measured low levels of autophagy in human acute myeloid leukemia samples, while we demonstrate that this provides a growth advantage to AML growth in vivo (Watson et al, Cell Death Discovery 2015).

The survival of memory T cells is also reliant on autophagy. We find that inducing autophagy in the aged T cells with a drug reverses an inefficient memory T cell response to influenza vaccination (Puleston et al, elife, 2014).

We are now trying to understand the role of autophagy in differentiation and metabolism, and identify novel druggable pathways of autophagy in hematopoietic cells and immune cells.

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