A5044359653- Neuroblastoma Research and Treatments
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Viral Infections and Immunology Research
- RNA modifications and cancer
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Cancer-related gene regulation
- Lung Cancer Research Studies
- Cancer-related molecular mechanisms research
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Ubiquitin and proteasome pathways
- Nanoparticle-Based Drug Delivery
- Protein Kinase Regulation and GTPase Signaling
- Signaling Pathways in Disease
- Retinoids in leukemia and cellular processes
- Nanoplatforms for cancer theranostics
- Neuroendocrine Tumor Research Advances
- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Estrogen and related hormone effects
Children's Cancer Institute Australia
2011-2024
UNSW Sydney
2012-2024
Novant Health
2024
Martin Luther University Halle-Wittenberg
2012-2023
Luther University
2023
Australian National University
2014-2021
Cancer Institute of New South Wales
2021
AID Atlanta
2020
Office of Science
2020
Center for Surveillance, Epidemiology, and Laboratory Services
2020
Background Patients with neuroblastoma due to the amplification of a 130-kb genomic DNA region containing MYCN oncogene have poor prognoses.
MYCN gene amplification in neuroblastoma drives a expression program that correlates strongly with aggressive disease. Mechanistically, trimethylation of histone H3 lysine 4 (H3K4) at target promoters is strict prerequisite for this transcriptional to be enacted. WDR5 H3K4 presenter has been found have an essential role trimethylation. For reason, study, we investigated the relationship between WDR5-mediated and N-Myc programs cells. upregulated Gene analysis revealed genes included those...
Abstract Chromosome 17q21-ter is commonly gained in neuroblastoma, but it unclear which gene the region important for tumorigenesis. The JMJD6 at activates transcription. Here we show that forms protein complexes with N-Myc and BRD4, E2F2, c-Myc Knocking down reduces neuroblastoma cell proliferation survival vitro tumor progression mice, high levels of expression human tissues independently predict poor patient prognosis. In addition, associated transcriptional super-enhancers. Combination...
Abstract Background Neuroblastoma is the most common solid tumor in infants accounting for approximately 15% of all cancer-related deaths. Over 50% high-risk neuroblastoma relapse, emphasizing need novel drug targets and therapeutic strategies. In neuroblastoma, chromosomal gains at chromosome 17q, including IGF2BP1 , MYCN amplification 2p are associated with adverse outcome. Recent, pre-clinical evidence indicates feasibility direct indirect targeting cancer treatment. Methods Candidate...
The TRIM family of proteins is distinguished by its tripartite motif (TRIM). Typically, contain a RING finger domain, one or two B-box domains, coiled-coil domain and the more variable C-terminal domains. TRIM16 does not have but harbour Here we showed that homodimerized through heterodimerized with other members; TRIM24, Promyelocytic leukaemia (PML) protein Midline-1 (MID1). Although, has no classic three-dimensional modelling suggested domains adopts RING-like folds leading to hypothesis...
Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L the only known histone methyltransferase that catalyzes H3K79 methylation. Here, we show N-Myc upregulates mRNA protein binding to promoter. shRNA-mediated depletion reduced genes ODC1 E2F2 bound Box II domain protein, knockdown neuroblastoma...
Chromosomal 17q21-ter gain in neuroblastoma is both a common and prognostically significant event. The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) gene located near the proximal edge of this region. Here, its prognostic value evaluated neuroblastoma.The mRNA expression IGF2BP family members was first by microarray data sets. In addition, separate cohort 69 tumors, IGF2BP1 copy number, mRNA, abundance were determined compared with clinical parameters.In two independent sets,...
Pneumoconioses are preventable occupational lung diseases caused by inhaling dust particles such as coal or different types of mineral dusts (1). To assess recent trends in deaths associated with pneumoconiosis, CDC analyzed multiple cause-of-death data*,† for decedents aged ≥15 years the 1999-2018, and industry occupation data collected from 26 states§ 1999, 2003, 2004, 2007-2013. During pneumoconiosis decreased 40.4%, exception attributed to other inorganic (e.g., aluminum, bauxite,...
Metastatic cancer cells exploit Epithelial-mesenchymal-transition (EMT) to enhance their migration, invasion, and resistance treatments. Recent studies highlight that elevated levels of copper are implicated in progression metastasis. Clinical trials using chelators associated with improved patient survival; however, the molecular mechanisms by which depletion inhibits tumor metastasis poorly understood. This remains a major hurdle clinical translation chelators. Here, we propose chelation...
The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but often characterized by critical protein–protein interactions necessary for their function. TRIM16 is induced different cancer types, when the cell forced to proceed down a differentiation pathway. We have identified as DNA-binding protein with histone acetylase activity, which required retinoic acid receptor β2 transcriptional response retinoid-treated cells. In this study, we show that...
Neuroblastoma is the most common solid tumor in childhood and represents 15% of all children's cancer deaths. We have previously demonstrated that tripartite motif 16 (TRIM16), a member RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has significant effects on neuroblastoma proliferation migration vitro tumorigenicity vivo. However, mechanism by which this putative suppressor influences cell was undetermined. Here we show, for first time, TRIM16's striking pattern...
Melanoma is the most dangerous form of skin cancer with majority deaths arising from metastatic disease. Evidence implicates Rho-activated gene transcription in melanoma metastasis mediated by nuclear localization transcriptional coactivator, myocardin-related factor (MRTF). Here, we highlight a role for Rho and MRTF signaling its reversal pharmacologic inhibition using vitro vivo models human growth metastasis. Using two cellular melanoma, clearly show that one cell type, SK-Mel-147, highly...
Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of thyroid. Selective molecular markers and drivers distinguishing ATC from other follicular origin remain largely unknown, limiting advances in diagnosis treatment. In a retrospective study, we analyzed gene expression 36 ATC, 18 poorly differentiated, 132 papillary, 55 carcinoma, as well 124 paired unpaired normal tissues three independent cohorts by RNA-sequencing immunohistochemistry. data test cohort...
Abstract Retinoid therapy is used for chemo‐prevention in immuno‐suppressed patients at high risk of developing skin cancer. The retinoid signalling molecule, tripartite motif protein 16 (TRIM16), a regulator keratinocyte differentiation and tumour suppressor retinoid‐sensitive neuroblastoma. We sought to determine the role TRIM16 squamous cell carcinoma (SCC) pathogenesis. have shown that expression was markedly reduced during histological progression from normal actinic keratosis SCC. SCC...
MYCN is a major driver for the childhood cancer, neuroblastoma, however, there are no inhibitors of this target. Enhanced protein stability key component oncogenesis and maintained by multiple feedforward expression loops involving transactivation target genes. Here, we reveal oncogenic role novel binding protein, proliferation-associated 2AG4 (PA2G4). Chromatin immunoprecipitation studies demonstrated that occupies PA2G4 gene promoter, stimulating transcription. Direct to blocked...
MYCN gene amplification and upregulated expression are major hallmarks in the progression of high-risk neuroblastoma. function modulating synthesis neuroblastoma is controlled at virtually every level, including poorly understood regulation post-transcriptional level. modulates various microRNAs miR-17-92 cluster. mRNA itself subjected to control by miRNAs, most prominently cluster that balances feed-back regulation. This homeostasis seems disturbed where upregulation coincides with severely...
Neuroblastoma is a common childhood cancer with almost third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development patient outcome, the role RBPs relatively unstudied. In order elucidate novel involved MYCN-amplified high-risk subtypes, we performed...