Haematology Research

Lab head: Freda Janet Passam
Location: Heart Reserach Institute Labs, Level 3 East, Charles Perkins Centre

Redox biomarkers in thrombotic disease.

Primary supervisor: Freda Passam

Aim: To identify new biological markers that can be used in the monitoring and treatment of patients with thrombotic disease.

Background: The redox balance (balance of reduction and oxidation reactions in our blood) is essential for a healthy circulation. Redox imbalance causes alterations of protein function contributing to the development of thrombosis. The Haematology Research group is focused on redox modification of disulphide bonds in two proteins critical for thrombus formation: the platelet receptor integrin a2bb3 and the plasma protein von Willebrand factor. We have found that reduced disulphide forms of a2bb3 and vWF have decreased thrombotic activity and may therefore protect from thrombotic disease, such as venous clots.

Project overview: We have developed assays which measure the redox balance in blood including tests which measure the disulphide reducing activity of plasma and the production of reactive oxygen species by platelets. We will study the redox modifications of platelet a2bb3 and plasma vWF which occur in patients at high risk for thrombosis to identify those most likely to benefit from drugs which restore the normal redox balance.

Techniques: This project employs mass spectrometry to study the posttranslational modifications of clotting proteins using disulphide labels specifically developed for this purpose. It also involves plasma and platelet functional assays.

Relevant publications:

1. Karimi Galougahi K, Antoniades C, Nicholls SJ, Channon KM, Figtree GA. Redox biomarkers in cardiovascular medicine. Eur Heart J. 2015;36(25):1576-1582

2. Passam F, Chiu J, Ju L, Pijning A, Jahan Z, Mor-Cohen R, Yeheskel A, Kolšek K, Thärichen L, Aponte-Santamaría C, Gräter F, Hogg PJ. Mechano-redox control of integrin de-adhesion. Elife. 2018, Jun 22

3. Butera D, Passam F, Ju L, Cook KM, Woon H, Aponte-Santamaría C, Gardiner E, Davis AK, Murphy DA, Bronowska A, Luken BM, Baldauf C, Jackson S, Andrews R, Gräter F, Hogg PJ. Autoregulation of von Willebrand factor function by a disulfide bond switch. Sci Adv. 2018 Feb 28

Discipline: Pathology
Co-supervisors: Joyce Chiu
Keywords: Redox biochemistry, Thrombosis, Biological markers