Dr Emma Josefsson
Division: Cancer & Haematology
Platelets are the blood cells that protect us from bleeding to death when we suffer a cut or other injury, quickly forming a plug that seals the wound.
Platelets lack nuclei and were long believed to be simplistic cell fragments. However, in recent years they have been shown to be a source of growth factors supporting tissue regeneration, having the ability to pick up and deliver chemicals, induce inflammation, alert immune cells, and attack microbes to mention a few functions.
In contrast to their protective roles, platelets are also involved in pathological thrombus formation during heart attack and stroke, and contribute to tumour metastasis.
Platelets are generated from large cells in the bone marrow called megakaryocytes. 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 specialized form of programmed cell death, apoptosis, in order to produce platelets.
We recently showed that megakaryocytes do not activate this pathway to facilitate platelet shedding, rather, the opposite is true: they must restrain it in order to survive and produce platelets. 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.
Together with the Kile laboratory, we are continuing to investigate the role of multiple cell death pathways in platelet production and function in health and disease. Furthermore, our group is investigating the role of platelets in blood cancer and metastasis.
- The role of apoptosis in platelet production and function in health and disease
- Platelet function in cancer progression
- *Debrincat MA, *Josefsson EC, *James C, Henley KJ, Ellis S, Lebois M, Betterman KL, Lane RM, Rogers KL, White MJ, Roberts AW, Harvey NL, Metcalf D, Kile BT. Mcl-1 and Bcl-xL co-ordinately regulate megakaryocyte survival. Blood. 2012 119(24):5850-8 PMID: 22374700. *Joint First Authors
- *Jansen AJ, *Josefsson EC, Rumjantseva V, Liu QP, Falet H, Bergmeier W, Cifuni SM, Sackstein R, von Andrian UH, Wagner DD, Hartwig JH, Hoffmeister KM. Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice. Blood. 2012 119(5):1263-73. PMID: 22101895. *Joint First Authors
- Josefsson EC, White MJ, Dowling MR, Kile BT. Platelet life span and apoptosis. Methods Mol Biol. 2012 788:59-71. PMID: 22130700.
- Josefsson EC, James C, Henley KJ, Debrincat MA, Rogers KL, Dowling MR, White MJ, Kruse EA, Lane RM, Ellis S, Nurden P, Mason KD, O'Reilly LA, Roberts AW, Metcalf D, Huang DC, Kile BT. Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. J Exp Med. 2011 208(10):2017-31. PMID: 21911424
- *Dowling MR, *Josefsson EC, Henley KJ, Hodgkin PD, Kile BT. Platelet senescence is regulated by an internal timer, not damage inflicted by hits. Blood. 2010 116(10):1776-8. PMID: 20530288. *Joint First Authors
- Rumjantseva V, Grewal PK, Wandall HH, Josefsson EC, Sørensen AL, Larson G, Marth JD, Hartwig JH, Hoffmeister KM. Dual roles for hepatic lectin receptors in the clearance of chilled platelets. Nat Med. 2009 15(11):1273-80. PMID: 19783995.
- Schoenwaelder SM, Yuan Y, Josefsson EC, White MJ, Yao Y, Mason KD, O'Reilly LA, Henley KJ, Ono A, Hsiao S, Willcox A, Roberts AW, Huang DC, Salem HH, Kile BT, Jackson SP. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood. 2009 114(3):663-6. PMID: 19387006.
- Josefsson EC, Gebhard HH, Stossel TP, Hartwig JH, Hoffmeister KM. The macrophage αMβ2 integrin αM lectin domain mediates the phagocytosis of chilled platelets. J Biol Chem. 2005 280(18):18025-32. PMID: 15741160.
- Hoffmeister KM, Josefsson EC, Isaac NA, Clausen H, Hartwig JH, Stossel TP. Glycosylation restores survival of chilled blood platelets. Science. 2003 301(5639):1531-4. PMID: 12970565.
Current Laboratory Members
Faculty Member: Emma Josefsson, MSc PhD Gothenburg, Sweden
Research Assistant: Marion Lebois, BSc Marseille MSc Paris XI
Research Assistant: Ping Cannon, BSc Shanghai
Honours Student: Starling Sim, B-BMED Melb
UROP Student: Jonathan Bernardini, Melb