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Souradip Mookerjee

Departments and Institutes

Department of Haematology:

Research Interests

Title: Supercharged platelets as novel therapeutics

Abstract: Platelets are the smallest blood cells whose primary function is haemostasis through release of platelet granules that activate neighbouring platelets to which they aggregate. Every year 280,000 units of platelets are transfused in the UK, 40% of which are transfused to patients actively bleeding with a low platelet count. The host lab has published and patented a methodology for the production of platelets in vitro from human pluripotent stem cells.

Systemic recombinant factor VIIa (the protein that triggers the clotting cascade) has been used to limit blood loss in trauma patients and following surgery, but its use has been limited by potential thrombotic adverse events. Platelets degranulate at the site of injury and therefore can act as targeted delivery vehicles for factor VIIa, potentially preserving the beneficial effect on local haemostasis, whilst preventing the risk of thrombosis.

The loss of heart muscle is the major factor responsible for the long-term morbi-/mortality following myocardial infarction. Two approaches to address this issue are the promotion of new vessel growth and the regrowth on cardiomyocytes, using members of the VEGF and EGF families of proteins. It has already been shown that platelets home to the injured myocardium in a mouse model of MI, and they would be ideal candidates for the targeted delivery of growth factors to the injured tissue.

I aim to explore the potential for engineered platelets as delivery vehicles for these issues in vitro and in vivo.

Keywords

platelets

Collaborators

Key Publications

Du LM, Nurden P, Nurden AT, Nichols TC, Bellinger DA, Jensen ES, Haberichter SL, Merricks E, Raymer RA, Fang J, Koukouritaki SB, Jacobi PM, Hawkins TB, Cornetta K, Shi Q, Wilcox DA. Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A. Nat Commun. 2013; 4: 2773.

Moreau T, Evans AL, Vasquez L, Tijssen MR, Yan Y, Trotter MW, Howard D, Colzani M, Arumugam M, Wu WH, Dalby A, Lampela R, Bouet G, Hobbs CM, Pask DC, Payne H, Ponomaryov T, Brill A, Soranzo N, Ouwehand WH, Pedersen RA, Ghevaert C. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nat Commun. 2016; 7: 11208.

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