A5014685459- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Cutaneous Melanoma Detection and Management
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- melanin and skin pigmentation
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Inflammasome and immune disorders
- Cardiac, Anesthesia and Surgical Outcomes
- Enhanced Recovery After Surgery
- Autophagy in Disease and Therapy
- Skin Protection and Aging
- Muscle metabolism and nutrition
- Biblical Studies and Interpretation
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
Melanoma Institute Australia
2015-2024
Centenary Institute
2015-2024
The University of Sydney
2013-2024
University of Worcester
2023
Royal Prince Alfred Hospital
2018-2021
Université Paris Sciences et Lettres
2018-2019
Inserm
2011-2019
Institut Curie
2010-2019
Université Paris-Saclay
2018-2019
Centre National de la Recherche Scientifique
2011-2019
The effect of hypercholesterolemia on vascular function was studied in humans. To eliminate the potential confounding effects atherosclerosis, reactivity measured forearm resistance vessels 11 normal subjects (serum LDL cholesterol = 111 +/- 7 mg/dl) and 13 patients with 211 19 mg/dl, P less than 0.05). Each subject received intrabrachial artery infusions methacholine, which releases endothelium-derived relaxant factor, nitroprusside directly stimulates guanylate cyclase smooth muscle....
Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose this study was to determine whether infusion L-arginine, precursor endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent hypercholesterolemic humans. Vascular reactivity measured forearm resistance vessels 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia 4.65...
Monoclonal antibodies against immune checkpoint blockade have proven to be a major success in the treatment of melanoma. The programmed death receptor-1 ligand-1 (PD-L1) expression on melanoma cells is believed an inhibitory effect T cell responses and important escape mechanism from attack. Previous studies shown that PD-L1 can expressed constitutively or induced by IFN-γ secreted infiltrating lymphocytes. In present study we investigated underlying these two modes including had acquired...
While multiple mechanisms of BRAFV600-mutant melanoma resistance to targeted MAPK signaling inhibitors (MAPKi) have been reported, the epigenetic regulation this process remains undetermined. Here, using a CRISPR-Cas9 screen targeting chromatin regulators, we discover that haploinsufficiency histone deacetylase SIRT6 allows cell persistence in presence MAPKi. Haploinsufficiency, but not complete loss promotes IGFBP2 expression via increased accessibility, H3K56 acetylation at locus, and...
Constitutive expression of the immune checkpoint, PD-L1, inhibits anti-tumor responses in cancer, although factors involved PD-L1 regulation are poorly understood. Here we show that loss global DNA methylation, particularly intergenic regions and repeat elements, is associated with constitutive (PD-L1CON), versus inducible (PD-L1IND), melanoma cell lines. We further this accompanied by transcriptomic up-regulation. De novo epigenetic regulators (e.g., DNMT3A) strongly correlated methylome...
// Jessamy C. Tiffen 1, 2, 8 , Dilini Gunatilake Stuart J. Gallagher Kavitha Gowrishankar Anja Heinemann Carleen Cullinane 3 Ken Dutton-Regester 4 Gulietta M. Pupo 5 Dario Strbenac 6 Jean Y. Yang Jason Madore 7, Graham Mann 5, 6, Nicholas K. Hayward Grant A. McArthur 3, 9 Fabian V. Filipp 10 Peter Hersey 1 Melanoma Immunology and Oncology Group, Centenary Institute, University of Sydney, NSW, Australia 2 Research Kolling Institute Medical Research, Translational Laboratory, MacCallum Cancer...
// Anja Heinemann 1, 2, 3 , Carleen Cullinane 4 Ricardo De Paoli-Iseppi 5 James S. Wilmott Dilini Gunatilake Jason Madore Dario Strbenac 6 Jean Y. Yang Kavitha Gowrishankar 2 Jessamy C. Tiffen Rab K. Prinjha 7 Nicholas Smithers Grant A. McArthur Peter Hersey Stuart J. Gallagher 1 Melanoma Research Group, Kolling Institute of Medical Research, University Sydney, St Leonards NSW, Australia Australia, North Immunology and Oncology Centenary Institute, Camperdown, Translational Laboratory,...
Summary The transcription factor NF ‐kappa B ( ‐ kB ) is a key regulator of cytokine and chemokine production in melanoma responsible for symptoms such as anorexia, fatigue, weight loss. In addition, believed to contribute progression the disease by upregulation cell cycle anti‐apoptotic genes resistance against targeted therapies immunotherapy. this study, we have examined ability bromodomain extra‐terminal BET protein inhibitor I 151 inhibit cells. We show that potent, selective number...
Cell migration is a key biological process with role in both physiological and pathological conditions. Locomotion of cells during embryonic development essential for their correct positioning the organism; immune have to migrate circulate response injury. Failure or an inappropriate acquisition migratory capacities can result severe defects such as altered pigmentation, skull limb abnormalities development, defective wound repair, immunosuppression tumor dissemination. The ability...
Although the introduction of selective v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors has been a major advance in treatment metastatic melanoma, approximately 50% patients have limited responses including stabilization disease or no response at all. This study aims to identify novel means overcoming resistance melanoma killing by BRAF inhibitors. We examined influence BH3-mimetic ABT-737 on induction apoptosis inhibitor PLX4720 cells with without V600E mutation. Included...
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy cancer is an important goal in this new era immunotherapy. Hepatitis due to immunotherapy antibodies against PD-1 uncommon and generally low severity. We present unusually severe case arising a melanoma patient after more than 6 months uncomplicated anti-PD-1 adjuvant setting. The hepatitis rapidly developed resistance high-dose steroids, requiring anti-thymocyte globulin (ATG) achieve...
Mutations in BRAF activate oncogenic MAPK signalling almost half of cutaneous melanomas. Inhibitors (BRAFi) and its target MEK are widely used to treat melanoma patients with mutations but unfortunately acquired resistance occurs the majority patients. Resistance results from or non‐genomic changes that either reactivate other pathways provide alternate survival growth signalling. Here, we show histone deacetylase inhibitor (HDACi) panobinostat overcomes BRAFi melanoma, this is dependent on...
The epigenetic modifier EZH2 is in the center of a repressive complex controlling differentiation normal cells. In cancer has been implicated silencing tumor suppressor genes. Its role melanoma as well target genes affected by are poorly understood. view this we have used an integrated systems biology approach to analyze 471 cases skin cutaneous (SKCM) Cancer Genome Atlas (TCGA) for mutations and amplifications EZH2. Identified changes were validated interrogation microarray data from cells...
Metastatic cutaneous melanoma is highly resistant to cytotoxic drugs, and this contributes poor prognosis. In vivo studies on the chemosensitivity of metastatic are rare hampered by response rates systemic chemotherapeutics. Patients who undergo isolated limb infusion (ILI) with drugs show high are, therefore, a good cohort for studying in vivo. We used tumors from patients underwent ILI study role tumor-suppressor genes oncogenes chemosensitivity. Prospectively acquired 30 subsequently...