Emma Josefsson-Projects

Emma Josefsson-Projects


The role of apoptosis in platelet production and function in health and disease

The process by which megakaryocytes produce platelets is unique and involves polyploidisation and shedding of platelets into the blood stream. The exact nature of this process is controversial, however it has been widely held that megakaryocytes undergo a specialised form of programmed cell death, apoptosis, in order to produce platelets.

We recently showed that this is not the case. Rather, megakaryocytes must restrain apoptosis in order to survive and produce platelets (Josefsson, J Exp Med 2011 208(10):2017, Josefsson, Nat Commun 2014 5(3455)). This discovery has important implications for our understanding of human diseases where the apoptotic death of megakaryocytes has been implicated and helps pinpointing the pathways chemotherapies might trigger in megakaryocytes and their precursors.

We are continuing to investigate the role of multiple cell death pathways in platelet production and function in health and disease.

Project resource: Cross-section of a megakaryocyte. Nuclei in blue (DAPI) and the integrin receptor (CD41) in green. Confocal microscopy by Dr Josefsson. 


Platelet function in cancer progression

As early as 1968, platelet counts below normal were shown to be protective against tumour cell metastases in mice (Gasic, Proc Natl Acad Sci USA 1968 61(1):46). However, the mechanism(s) of this effect (Gay, Nat Rev Cancer 2011 11(2):123) and its relevance to the biology of human malignancies has been uncertain.

Clinical studies have shown that patients who receive long-term treatment with platelet inhibitors like aspirin present a lower risk of metastasising tumours (Rothwell Lancet 2011 377(9759):31). In recent studies, platelet counts above normal have been associated with advanced disease and shortened survival, but definitive mechanistic insights are lacking.

This project will investigate the molecular regulation of platelet production and function in the progression of solid tumours.