Size as a driver of stem cell ageing and cancer

The failure to regenerate tissues with age underlies some of the most challenging health issues in elderly. A main contributor to this decline is the loss of stem cell function.

Despite the essential role of stem cells, how they fail to maintain their functions during ageing and disease is still unclear. I discovered a new aspect of stem cell ageing in vivo: cellular enlargement. With age and damage, stem cells increase in size causing their functional decline.

However, how size impacts stem cells fitness and the physiological importance of this process remains unsolved.In my independent lab at the Karolinska Institutet, I will to address these key questions by (1) identifying pathways that cause stem cell dysfunction during age-dependent enlargement and (2) illuminating the effect of stem cell enlargement on cancer.Based on my preliminary data, I hypothesize that enlargement creates a cellular energy deficit, which drives stem cell dysfunction and at the same time prevents their transformation into cancerous cells.

Using hematopoietic stem cells of mouse models, my lab will identify the molecular mechanisms impairing fitness of large stem cells by following up on a targeted approach.

We will then utilize differently sized, oncogenic stem cells from mice and humans to test their potential to affect leukemia.The novel insights into the molecular mechanisms of size-dependent stem cell fitness and its role in cancer will be of significant scientific and therapeutic value.