A5034233092- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Telomeres, Telomerase, and Senescence
- Angiogenesis and VEGF in Cancer
- Hippo pathway signaling and YAP/TAZ
- Platelet Disorders and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Barrier Structure and Function Studies
- Caveolin-1 and cellular processes
- Intracerebral and Subarachnoid Hemorrhage Research
- Vascular Malformations Diagnosis and Treatment
- Protease and Inhibitor Mechanisms
- Sphingolipid Metabolism and Signaling
- Glaucoma and retinal disorders
- Endoplasmic Reticulum Stress and Disease
- Blood disorders and treatments
- Counseling, Therapy, and Family Dynamics
- Moyamoya disease diagnosis and treatment
- Wnt/β-catenin signaling in development and cancer
- Advanced Fluorescence Microscopy Techniques
- Photosynthetic Processes and Mechanisms
- Ocular and Laser Science Research
- SARS-CoV-2 and COVID-19 Research
- Adipokines, Inflammation, and Metabolic Diseases
- Skin Protection and Aging
Centenary Institute
2010-2025
The University of Sydney
2013-2024
The Heart Research Institute
2021-2024
Centre for Cancer Biology
2019
Cooperative Trials Group for Neuro-Oncology
2018
Endometriosis
2014
Abstract Alzheimer’s disease (AD) is an age-related disease, with loss of integrity the blood–brain barrier (BBB) being early feature. Cellular senescence one reported nine hallmarks aging. Here, we show for first time presence senescent cells in vasculature AD patients and mouse models AD. Senescent endothelial pericytes are present APP/PS1 transgenic mice but not wild-type littermates at amyloid deposition. In vitro, display altered VE-cadherin expression cell junction formation increased...
Abstract Background Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), well-established pro-cancer enzyme, is aberrantly overexpressed in multitude of malignancies, including HCC. Our previous research has shown that genetic ablation Sphk1 mitigates HCC progression mice. Therefore, the development PF-543, highly selective SphK1 inhibitor, opens new avenue treatment....
Platelet activation induces the secretion of proteins that promote platelet aggregation and inflammation. However, detailed analysis released proteome is hampered by platelets' tendency to pre-activate during their isolation a lack sensitive protocols for low abundance releasate analysis. Here we detail most date with detection >1,300 proteins. Unbiased scanning post-translational modifications within highlighted O-glycosylation as being major component. For first time, detected...
The formation of the vascular network requires a tightly controlled balance pro-angiogenic and stabilizing signals. Perturbation this can result in dysregulated blood vessel morphogenesis drive pathologies including cancer. Here, we have identified novel gene, ARHGAP18, as an endogenous negative regulator angiogenesis, limiting signaling promoting stability. Loss ARHGAP18 promotes EC hypersprouting during zebrafish murine retinal development enhances tumor vascularization growth. Endogenous...
Cerebral cavernous malformations (CCMs) are vascular lesions predominantly developing in the central nervous system (CNS), with no effective treatments other than surgery. Loss-of-function mutation CCM1/krev interaction trapped 1 (KRIT1), CCM2, or CCM3/programmed cell death 10 (PDCD10) causes that characterized by abnormal integrity. Vascular endothelial cadherin (VE-cadherin), a major regulator of (EC) junctional integrity is strongly disorganized ECs lining CCM lesions. We report here...
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, but serious, complication of the ChAdOx1 nCOV-19 vaccine. In Australia, diagnosis VITT required detection antibodies against platelet factor 4 (PF4) in plasma using PF4/polyanion ELISA. Half patients, fulfilling clinical criteria VITT, tested positive this ELISA and another third activation assays, highlighting limitations assays used for VITT. Utilizing microfluidic device coated with endothelial cells, Endo-chip, we...
Age is the greatest risk factor for cardiovascular disease. In addition, inflammation and age (senescence) have been linked at both clinical molecular levels. general, senescent cells described as pro-inflammatory based on their senescence associated secretory phenotype (SASP). However, we previously shown that induced by overexpression of SENEX (or ARHGAP18), in endothelial results an anti-inflammatory phenotype. We investigated, individual cellular level, following three chief signals with...
Summary Senescent endothelial cells ( EC ) have been identified in cardiovascular disease, angiogenic tumour associated vessels and aged individuals. We previously a novel anti‐inflammatory senescent phenotype of . show here that caveolae are critical the induction this state. induced by either overexpression ARHGAP18/SENEX or H 2 O showed significantly increased numbers proteins Caveolin‐1, cavin‐1 cavin‐2. Depletion these RNA interference decreased senescence ARHGAP18 predominantly...
RhoGTPases are important regulators of the cell cytoskeleton, controlling shape, migration and proliferation. Previously we showed that ARHGAP18 in endothelial cells is junctions. Here show, using structured illumination microscopy (SIM), ground-state depletion (GSD), total internal reflection fluorescence (TIRF) a proportion localizes to microtubules cells, as well nonendothelial an association confirmed biochemically. In some puncta also colocalized Weibel-Palade bodies on microtubules....
// Jinbiao Chen 1, 7 , Yanfei Qi 2 Yang Zhao Dominik Kaczorowski 1 Timothy A. Couttas 3 Paul R. Coleman Anthony S. Don Patrick Bertolino 4 Jennifer Gamble 2, * Mathew Vadas Pu Xia 5, and Geoffrey W. McCaughan 6, 7, Liver Injury Cancer, Camperdown, NSW 2050, Australia Vascular Biology, ACRF Centenary Cancer Research, Immunology in Institute, 5 Department of Endocrinology Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China 6 A.W. Morrow Gastroenterology Center, Australian...
Abstract Background Vascular endothelial cell alignment in the direction of flow is an adaptive response that protects against aortic diseases such as atherosclerosis. The RhoGTPases are known to regulate this alignment. We have shown previously ARHGAP18 cells a negative regulator RhoC and its expression essential flow-mediated Depletion inhibits results induction pro-inflammatory phenotype. In embryogenesis, was identified downstream effector Yes-associated protein, YAP, which regulates...
Vascular normalisation, the process that reverses structural and functional abnormalities seen in tumour-associated vessels, is also accompanied by changes leucocyte trafficking. Our previous studies have shown normalisation effects of agent CD5-2 which acts to stabilise VE-Cadherin leading increased penetration CD8+ T cells but decreased infiltration neutrophils (CD11b+Gr1hi) into tumour parenchyma. In present study, we demonstrate stabilisation through treatment purified endothelial (ECs)...
Microfluidic devices have an established role in the study of platelets and coagulation factors thrombosis, with potential diagnostic applications. However, few microfluidic assessed contribution neutrophils to thrombus formation, despite increasing knowledge neutrophils’ importance cardiovascular thrombosis. We describe a thromboinflammation model which uses straight channels, lined fixed human umbilical vein endothelial cells, after treatment tumour necrosis factor-alpha. Re-calcified...
Background Vascular endothelial cell (EC) alignment in the direction of flow is an adaptive response that protects against aortic diseases, such as atherosclerosis. The Rho GTP ases are known to regulate this alignment. Herein, we analyze effect ARHGAP 18 on regulation EC and examine deficiency development atherosclerosis mice. Methods Results We used vitro analysis ECs under conditions together with apolipoprotein E −/− Arhgap double‐mutant mice study function a high‐fat diet–induced model...
Abstract COVID-19 causes a clinical spectrum of acute and chronic illness host / virus interactions are not completely understood 1,2 . To identify factors that can influence SARS-CoV-2 infection, we screened the human genome for genes that, when upregulated, alter outcome authentic infection. From this, 34 new course including innate immune receptor P-selectin, which show is novel spike receptor. At cellular level expression P-selectin does confer tropism SARS-CoV-2, instead it acts to...