Associate ProfessorFreda Passam

Current Projects

Project 1

"Stressed" platelets in diabetes

Platelet hyperactivity, the increased sensitivity of platelets to activate in response to stimuli, significantly predisposes individuals to cardiovascular events such as heart attack and stroke. Using unbiased proteomics analysis of human platelets, we identified that in platelets from individuals with type 2 diabetes have increased endoplasmic reticulum (ER) stress. We discovered that the beta subunit of the ER protein SEC61 is overexpressed in platelets with hyperglycemia and associates with increased cytoplasmic calcium. We aim to elucidate the connection between ER stress and platelet hyperreactivity. This project will use genetic and chemical approaches to investigate the role of calcium leak channels in platelet activity. It will evaluate the efficacy of SEC61 inhibitors to dampen platelet hyperactivity and improve cardiovascular outcomes.

Project 2

The endothelial "side" of thromboinflammation

Heparin induced thrombocytopenia (HIT) is a severe thrombotic condition triggered by auto-antibodies directed against platelet factor 4 (PF4), which assemble on the vascular endothelium. We have found that the endothelium upregulates tissue factor activity in response to HIT antibodies which drives thromboinflammation. We are investigating the interaction of lymphocytes with the endothelium in HIT and developing novel inhibitors of the HIT antibody to dampen the immune thrombotic response. This project utilizes an endothelialized microfluidic device (the Endo-chip), which simulates a human vessel. Immune thrombosis is measured after exposure to antibodies from patients with HIT. The Endo-chip is used to screen for novel treatments to prevent immune thrombosis.

Project 3

ER "brakes" in thrombopoiesis

Platelet production is a highly regulated process and involves megakaryocyte maturation and proplatelet formation in the bone marrow (thrombopoiesis). Thiol isomerases ERp57 and ERp5 regulate protein folding during megakaryocyte maturation. Bone marrow-on-chip models have only been established at a few centres worldwide. This project will develop and apply a miniaturized 3D bone marrow model with silk biomaterials that faithfully reproduces the bone marrow architecture and microcirculation. This model will be populated by megakaryocytes to study the production of platelets in response to genetic and pharmacological manipulation of ERp5 and ERp57. The aim of this study is to understand the role of ERp5 and ERp57 in thrombopoiesis.

Current Grants

2025 Drug Discovery initiative University of Sydney, Peripheral Artery Disease Priority Driven Program, CIA Mary Kavurma, CIB Freda Passam
2023 NHMRC Ideas Grants APP2030089 "Discovery of a new modification in the platelet proteome", CIA Mark Larance, CIB Freda Passam, $747,057

2022 NSW Health Cardiovascular Collaborative Grants, "Mechanisms of vascular thrombosis", CIA Vivien Chen, CIB Freda Passam, $1,000,000

2022 MRFF Cardiovascular Health Mission APP2023977 "Clinical imaging inspired point-of-care microtechnology for enhanced diagnosis and monitoring of recurrent stroke", CIA Arnold Lining Ju, CID Freda Passam, $1,199,996

2021 MRFF Cardiovascular Health Mission APP2017914 "Discovery of new platelet targets to improve the management of coronary artery disease", CIA Freda Passam, $659,293

2021 MRFF COVID-19 Vaccine-Associated Thrombosis with Thrombocytopenia Syndrome Grant Opportunity APP2015305 "A national, multi-centre study evaluating Thrombotic Thrombocytopenia Syndrome (TTS) associated with ChAdOx1 (AZD1222) and other SARS-CoV-2 vaccines (viral vector & m-RNA)", CIA Huyen Tran, CIH Freda Passam, $2,917,087

2020 NSW Health EMC Researcher Grant "Targets for the prevention of cardiovascular thrombosis in metabolic syndrome", CIA Freda Passam, $550,000