- Platelet Disorders and Treatments
- Venous Thromboembolism Diagnosis and Management
- Blood Coagulation and Thrombosis Mechanisms
- Antiplatelet Therapy and Cardiovascular Diseases
- Atrial Fibrillation Management and Outcomes
- Heparin-Induced Thrombocytopenia and Thrombosis
- Adipokines, Inflammation, and Metabolic Diseases
- Hemophilia Treatment and Research
- Blood properties and coagulation
- Atherosclerosis and Cardiovascular Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- COVID-19 Clinical Research Studies
- Cell Adhesion Molecules Research
- Acute Myocardial Infarction Research
- Inflammasome and immune disorders
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
- Extracellular vesicles in disease
- Central Venous Catheters and Hemodialysis
- Acute Ischemic Stroke Management
- Blood groups and transfusion
- Complement system in diseases
- Lipoproteins and Cardiovascular Health
- Chemokine receptors and signaling
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Baker Heart and Diabetes Institute
2016-2025
Australian Centre for HIV and Hepatitis Virology Research
2013-2025
Monash University
2016-2025
The Alfred Hospital
2016-2025
The University of Melbourne
2020-2025
Alfred Health
2014-2024
Royal Adelaide Hospital
2022
Universitäts-Herzzentrum Freiburg-Bad Krozingen
2021
University of Freiburg
2021
Melbourne Health
2020
Identifying the molecular mechanisms that promote optimal immune responses to coronavirus disease 2019 (COVID-19) vaccination is critical for future rational vaccine design. Here, we longitudinally profile innate and adaptive in 102 adults after first, second, third doses of mRNA or adenovirus-vectored COVID-19 vaccines. Using a multi-omics approach, identify key differences induced by ChAdOx1-S BNT162b2 correlate with antigen-specific antibody T cell reactogenicity. Unexpectedly, observe...
VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 antibodies within 42 days of Despite dysregulated lipid metabolism underpinning many thrombotic conditions, the role alterations in remains unexplored. Here, we examined plasma lipidome patients compared it those...
Thrombin is a central regulator of leukocyte recruitment and inflammation at sites vascular injury, function thought to involve primarily endothelial PAR cleavage. Here we demonstrate the existence distinct leukocyte-trafficking mechanism regulated by components haemostatic system, including platelet PAR4, GPIbα fibrin. Utilizing mouse injury model show that thrombin cleavage PAR4 promotes injury. This process negatively GPIbα, as seen in mice with abrogated thrombin-platelet binding...
PI3KC2α is a broadly expressed lipid kinase with critical functions during embryonic development but poorly defined roles in adult physiology. Here we utilize multiple mouse genetic models to uncover role for regulating the internal membrane reserve structure of megakaryocytes (demarcation system) and platelets (open canalicular that results dysregulated platelet adhesion under haemodynamic shear stress. Structural alterations lead enhanced tether formation associated accelerated, yet highly...
Certain patients with antibody-mediated autoimmune disease exhibit poor responses to conventional immunosuppression, including B-cell depletion rituximab. Proteasome inhibitors such as bortezomib demonstrate pleiotropic immunomodulatory effects, direct toxicity antibody-producing cells. Here, we report preliminary evidence for the efficacy of salvage therapy refractory hematological disease. Thirteen treatment episodes in 10 phenomena (autoimmune hemolytic anemia [AIHA; n = 8], acquired...
Article5 December 2022Open Access Source DataTransparent process A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein Johannes Zeller orcid.org/0000-0002-8122-9063 Department of Plastic and Hand Surgery, University Freiburg Medical Centre, Faculty the Freiburg, Germany Baker Heart Diabetes Institute, Melbourne, Vic., Australia Contribution: Conceptualization, Data curation, Formal analysis, Supervision, Validation, Investigation,...
Gut ischemia is common in critically ill patients, promoting thrombosis and inflammation distant organs. The mechanisms linking hemodynamic changes the gut to remote organ remain ill-defined. We demonstrate that mouse induces a distinct pulmonary thrombotic disorder triggered by neutrophil macroaggregates. These aggregates lead widespread occlusion of arteries, veins, microvasculature. A similar neutrophil-rich response occurred humans with acute respiratory distress syndrome. Intravital...
Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate activation, although the impact diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive activates integrin α
Microvesicles (MVs) are small cell-derived vesicles, which mainly released by activated cells. They part of a communication network delivering biomolecules, for example, inflammatory molecules, via the blood circulation to remote cells in body. Platelet-derived MVs known induce vascular inflammation. Research on mediators and mechanisms their effects has attracted major interest. We hypothesize that specific lipids inflammation caused platelet-derived MVs. Liquid chromatography electrospray...
RationaleThe early detection of primary tumours and metastatic disease is vital for successful therapy contingent upon highly specific molecular markers sensitive, non-invasive imaging techniques.We hypothesized that the accumulation activated platelets within a general phenomenon thus represents novel means cancer.Here we investigate unique single chain antibody (scFv), which specifically targets platelets, as biotechnological tool cancer.Methods The scFvGPIIb/IIIa, binds to form platelet...
Abstract Arterial thrombosis manifesting as heart attack and stroke is the leading cause of death worldwide. Platelets are central mediators that can be activated through multiple activation pathways. Platelet‐derived extracellular vesicles (pEVs), also known platelet‐derived microparticles, granular mixtures membrane structures produced by platelets in response to various activating stimuli. Initial studies have attracted interest on how platelet agonists influence composition pEV proteome....
Rationale: Platelets are increasingly recognized as mediators of tumor growth and metastasis.Hypothesizing that activated platelets in the microenvironment provide a targeting epitope for tumor-directed chemotherapy, we developed an antibody-drug conjugate (ADC), comprised single-chain antibody (scFv) against platelet integrin GPIIb/IIIa (scFvGPIIb/IIIa) linked to potent chemotherapeutic microtubule inhibitor, monomethyl auristatin E (MMAE).Methods: We ADC three components: 1) A scFv which...
Frailty and delirium are prevalent among older adults admitted to the intensive care unit (ICU) associated with adverse outcomes; however, their relationships have not been extensively explored. This study examined association between frailty mortality length of hospital stay (LOS) in ICU patients, whether associations mediated or modified by an episode delirium.Retrospective analysis data from Australian New Zealand Intensive Care Society Adult Patient Database. A total 149,320 patients...