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Our objective

Our mission is to discover new mechanisms of clot formation that can lead to the development of efficient and safer antithrombotic drugs.

We have a special interest in the development of biochips for the detection and monitoring of thrombotic tendency. We are focused on the role of enzymes, named thiol isomerases, in the development of thrombosis and their potential as novel antithrombotic targets. An exciting new project is to define the proteomic signature of the diabetic platelet to identify causes for increased thrombotic risk in patients with diabetes. In the clinical space, we are interested in the management of venous thrombosis in the community and high-risk thrombosis.

Our research goals are to: (i) discover new targets to prevent thrombotic complications in patients with diabetes; (ii) characterise thiol isomerase inhibitors as new antithrombotics; and (iii) develop new methods to detect prothrombotic tendency in patients with cardiovascular risk factors.

Our impact

Current antithrombotic treatment is not effective or has bleeding side effects, eg, one in six patients who have had a heart attack will have another attack despite optimal treatment. We aim to find answers to fundamental biological problems that will enable the development of new diagnostics and treatments for patients with blood clots. New diagnostics are important because routine tests are not able to detect a thrombotic tendency in half the cases. We are committed to discovering targets for new and safe antithrombotics.

Selected publications

Perdomo J, et al. Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia. Nat Commun 10, 1322 (2019). https://doi.org/10.1038/s41467-019-09160-7

Bekendam RH, et al. Protein disulfide isomerase regulation by nitric oxide maintains vascular quiescence and controls thrombus formation. J Thromb Haemost. 2018 Sep 12, IF:4.8.

Passam F, et al. Mechano-redox control of integrin de-adhesion. Elife. 2018 Jun 22;7, IF:7.7.

Lee KH, et al. Quantification of NETs-associated markers by flow cytometry and serum assays in patients with thrombosis and sepsis. Int J Lab Hematol. 2018 Mar 9, IF:1.9.

Butera D, et al. Autoregulation of von Willebrand factor function by a disulfide bond switch. Sci Adv. 2018 Feb 28;4(2), IF:11.5.

Dupuy A, et al. Functional assays of thiol isomerase ERp5. Methods in Molecular Biology 2018 [in press].

The team

Alexander Dupuy

PhD Student

Angelina Lay

Postdoctoral Fellow (Centenary Institute)

Callum Houlahan

Research Assistant

Neil Sullivan Alexis Mgaieth

Med Student (USYD)

Renee Preketes-Tardiani

Intern (Bioengineering, USYD)

Darryl Chiu

Honours Student (Biomed Sci/Bioengineering USyd)

Lejla Hagimola

Visiting Student (Med Sci/Business UTS)

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