A5067720195- Pancreatic function and diabetes
- Immune cells in cancer
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Immune Response and Inflammation
- Nanoplatforms for cancer theranostics
- Diabetes Management and Research
- Endoplasmic Reticulum Stress and Disease
- S100 Proteins and Annexins
- interferon and immune responses
- Cannabis and Cannabinoid Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genetics and Neurodevelopmental Disorders
- Metabolism, Diabetes, and Cancer
- Mesenchymal stem cell research
- Immunotherapy and Immune Responses
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Blood Coagulation and Thrombosis Mechanisms
- Cell death mechanisms and regulation
Garvan Institute of Medical Research
2016-2025
UNSW Sydney
2013-2025
University of Florida
2024
St Vincent's Clinic
2011-2023
Royal Adelaide Hospital
2018-2023
The Kinghorn Cancer Centre
2015-2023
The University of Adelaide
2016-2023
RELX Group (United States)
2023
University of Wisconsin–Madison
2018
University of Toronto
2018
Via a transcription factor, Foxp3, immunoregulatory CD4+CD25+ T cells (T reg cells) play an important role in suppressing the function of other cells. Adoptively transferring high numbers can reduce intensity immune response, thereby providing attractive prospect for inducing tolerance. Extending our previous findings, we describe vivo approach rapid expansion by injecting mice with interleukin (IL)-2 mixed particular IL-2 monoclonal antibody (mAb). Injection these IL-2–IL-2 mAb complexes...
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, underlying cause appears to relate defects in T cell tolerance or help B cells. Transgenic (Tg) mice overexpressing cytokine cell–activating factor tumor necrosis family (BAFF) develop an disorder similar SLE and show impaired altered differentiation. We generated BAFF Tg that were completely deficient cells, and, surprisingly, these developed SLE-like...
Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy impairs metastatic spread in pancreatic cancer.
Abstract Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote restrain disease progression. Here, we interrogate how cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence a p53-driven hierarchy, where with gain-of-function (GOF) mutant educate dominant population CAFs that establish pro-metastatic environment for GOF null alike. also demonstrate educated by may be reprogrammed either or...
Failure to secrete adequate amounts of insulin in response increasing concentrations glucose is an important feature type 2 diabetes. The mechanism for loss responsiveness unknown. Uncoupling protein (UCP2), by virtue its mitochondrial proton leak activity and consequent negative effect on ATP production, impairs glucose-stimulated secretion. Of interest, it has recently been shown that superoxide, when added isolated mitochondria, activates UCP2-mediated leak. Since obesity chronic...
AbstractActivating transcription factor 3 (ATF3) is a stress-inducible gene and encodes member of the ATF/CREB family factors. However, physiological significance ATF3 induction by stress signals not clear. In this report, we describe several lines evidence supporting role in stress-induced β-cell apoptosis. First, induced β cells relevant to destruction: proinflammatory cytokines, nitric oxide, high concentrations glucose palmitate. Second, mediated part NF-κB Jun N-terminal...
Failure to secrete adequate amounts of insulin in response increasing concentrations glucose is an important feature type 2 diabetes. The mechanism for loss responsiveness unknown. Uncoupling protein (UCP2), by virtue its mitochondrial proton leak activity and consequent negative effect on ATP production, impairs glucose-stimulated secretion. Of interest, it has recently been shown that superoxide, when added isolated mitochondria, activates UCP2-mediated leak. Since obesity chronic...
Recent studies have shown that infusion of the anticoagulant protein, activated protein C (APC), can ameliorate many systemic effects endotoxemia in experimental animals, although mechanisms this action are unknown. We investigated APC on responses blood monocytes, alveolar macrophages, and cells monocyte line, THP-1, to stimulation vitro by LPS, IFN-gamma, or PMA. Mononuclear phagocyte (MO) activation was associated with rapid production TNF-alpha, down-regulation...
Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that regulates cellular stress responses. While the levels of HIF-1alpha protein are tightly regulated, recent studies suggest it can be active under normoxic conditions. We hypothesized required for normal beta cell function and reserve dysregulation may contribute to pathogenesis type 2 diabetes (T2D). Here we show present at low in mouse human cells islets. Decreased impaired glucose-stimulated ATP generation function....
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease resulting from apoptotic destruction of β cells in the islets Langerhans. Low expression antioxidants and a predilection to produce nitric oxide (NO) have been shown underscore cell apoptosis. With this perspective mind, we questioned whether could mount induced protective response inflammation. Here show that human rat can be rapidly express antiapoptotic gene A20 after interleukin (IL)-1β activation. Overexpression by...
Hypertrophy is one mechanism of pancreatic β-cell growth and seen as an important compensatory response to insulin resistance. We hypothesized that the induction protective genes contributes survival enlarged (hypertrophied) β-cells. Here, we evaluated changes in stress gene expression accompany hypertrophy islets from hyperglycemic rats 4 weeks after partial pancreatectomy (Px). A variety were upregulated, with markedly increased antioxidant heme oxygenase-1 glutathione peroxidase...
Hyperglycemia in critical illness is a common complication and strong independent risk factor for morbidity death. Intensive insulin therapy decreases this by up to 50%. It unclear what extent benefit due reversal of glucotoxicity or direct effect insulin, because antiinflammatory effects have already been described, but the underlying mechanisms are still poorly understood. The receptor expressed on resting neutrophils, monocytes, B cells, not detectable T cells. However, significant...
Interferon-γ (IFN-γ)-preactivated mesenchymal stem cells (MSC-γ) are highly immunosuppressive but immunogenic in vivo due to their inherent expression of major histocompatibility (MHC) molecules. Here, we present an improved approach where modified human bone marrow-derived MSC with interleukin-17A (MSC-17) enhance T cell immunosuppression not immunogenicity. MSC-17, unlike MSC-γ, showed no induction or upregulation MHC class I, II, and costimulatory molecule CD40, maintained normal...
Objective Extensive molecular heterogeneity of pancreatic ductal adenocarcinoma (PDA), few effective therapies and high mortality make this disease a prime model for advancing development tailored therapies. The p16-cyclin D-cyclin-dependent kinase 4/6-retinoblastoma (RB) protein (CDK4) pathway, regulator cell proliferation, is deregulated in PDA. Our aim was to develop novel personalised treatment strategy PDA based on targeting CDK4. Design Sensitivity potent CDK4/6 inhibitor PD-0332991...
Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim this single-arm, multicenter study was to evaluate an immunosuppressive protocol antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching sirolimus MMF. Islets were cultured for 24 h prior transplantation. primary end-point HbA1c <7% cessation severe hypoglycemia. Seventeen recipients ≥ 12...
Influenza A virus (IAV) infections lead to severe inflammation in the airways. Patients with chronic obstructive pulmonary disease (COPD) characteristically have exaggerated airway and are more susceptible symptoms increased mortality. The mechanisms that control during IAV infection of immune dysregulation COPD unclear. We found inflammatory antiviral responses primary bronchial epithelial cells (pBECs) from healthy nonsmoking smoking subjects. In pBECs patients, resulted but deficient...
Highlights•Live quantification of RhoA activity during development and disease progression•Real-time visualization signaling in normal skin, osteocytes, neutrophils•Monitoring deregulation invasive mammary pancreatic cancers•Longitudinal vivo imaging inhibition using optical windowsSummaryThe small GTPase is involved a variety fundamental processes tissue. Spatiotemporal control thought to govern mechanosensing, growth, motility cells, while its associated with development. Here, we describe...
Journal Article Does Size Matter? Critical Mass and New Zealand's Women MPs Get access Sandra Grey Search for other works by this author on: Oxford Academic Google Scholar Parliamentary Affairs, Volume 55, Issue 1, 1 January 2002, Pages 19–29, https://doi.org/10.1093/parlij/55.1.19 Published: 01 2002
Apoptosis of hepatocytes is a seminal feature fulminant hepatic failure. We show that the anti-apoptotic protein A20 upregulated in by pro-inflammatory stimuli and functions to protect from apoptosis limit inflammation inhibiting NF-κB. Adenoviral mediated expression BALB/c mice yields an 85% survival rate D-galactosamine (D-gal)/lipolysaccharide (LPS) model acute toxic hepatitis compared with 15% 20 % control mice. Expression preserves normal liver function as assessed prothrombin time. The...
B cell-activating factor belonging to the TNF family (BAFF; BLyS) is a critical regulator of cell maturation and survival, its overexpression in BAFF transgenic (Tg) mice results development autoimmune disorders. also affects T function through binding one receptors, BAFF-R. Using Tg mice, we examined typical Th1-mediated response, cutaneous delayed-type hypersensitivity reaction, found much greater degree paw swelling inflammation than control mice. Importantly, scores correlated directly...