A5049918075- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- TGF-β signaling in diseases
- Wnt/β-catenin signaling in development and cancer
- Microtubule and mitosis dynamics
- Trace Elements in Health
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Telomeres, Telomerase, and Senescence
- Cancer, Hypoxia, and Metabolism
- Retinoids in leukemia and cellular processes
- Cellular Mechanics and Interactions
- Biological Research and Disease Studies
- Signaling Pathways in Disease
- Autoimmune and Inflammatory Disorders
- Clusterin in disease pathology
- RNA regulation and disease
- Systemic Lupus Erythematosus Research
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- Heterotopic Ossification and Related Conditions
- Mechanisms of cancer metastasis
Parks Victoria
2025
CSL (Australia)
2023
Peter MacCallum Cancer Centre
2013-2022
The University of Melbourne
2013-2022
St Vincents Institute of Medical Research
2013-2014
Universitat de Barcelona
2008-2011
Institut d'Investigació Biomédica de Bellvitge
2008-2011
Bellvitge University Hospital
2011
Cellular senescence is characterised by the irreversible arrest of proliferation, a pro-inflammatory secretory phenotype and evasion programmed cell death mechanisms. We report that alters cellular iron acquisition storage also impedes iron-mediated pathways. Senescent cells, regardless stimuli (irradiation, replicative or oncogenic), accumulate vast amounts intracellular (up to 30-fold) with concomitant changes in levels homeostasis proteins. For instance, ferritin (iron storage) provided...
Bone morphogenetic proteins (BMPs) are potent regulators of several cellular events. We report that exposure C2C12 cells to BMP2 leads an increase in cell migration and a rapid rearrangement the actin filaments into cortical protrusions. These effects required independent parallel activation Cdc42 small GTPase alpha-isoform phosphoinositide 3-kinase (PI3Kalpha), because ectopic expression dominant-negative form or distinct pharmacological PI3K inhibitors abrogated these responses....
Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) metabolic diabetes). We identified copper accumulation as being a universal...
Abstract The function of the tumor suppressor p53 is universally compromised in cancers. It most frequently mutated gene human cancers (reviewed). In cases where not mutated, alternative regulatory pathways inactivate its suppressive functions. This primarily achieved through elevation expression key inhibitors p53: Mdm2 or Mdmx (also called Mdm4) breast cancer (BrCa), frequency mutations varies markedly between different subtypes, with basal-like BrCas bearing a high mutations, whereas...
Background Bone morphogenetic proteins (BMPs) have been shown to participate in the patterning and specification of several tissues organs during development regulate cell growth, differentiation migration different types. BMP-mediated requires activation small GTPase Cdc42 LIMK1 activities. In our earlier report we showed that also PAKs through PI3K. However, requirement additional signaling is not clearly known. Methodology/Principal Findings Activation p38 MAPK has be relevant for a...
Mutation of the key tumour suppressor p53 defines a transition in progression towards aggressive and metastatic breast cancer (BC) with poorest outcome. Specifically, mutation frequency exceeds 50% triple-negative BC. Key regulators mutant that facilitate its oncogenic functions are potential therapeutic targets. We report here MDM4 protein is frequently abundant context basal-like BC samples. Importantly, we show plays critical role proliferation these cells. demonstrate conditional...
Abstract Background Neutrophils have been shown to contribute the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful and debilitating inflammatory skin disease, yet their exact role remains be fully defined. Granulocyte colony-stimulating factor (G-CSF), major regulator neutrophil development survival, can blocked by novel, human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. Objectives We investigated activation migration neutrophils in HS impact blocking G-CSFR...
Background Chronic Obstructive Pulmonary Disease (COPD) is a heterogenous disease where chronic inflammation implicated in airway remodeling and emphysema. The CD131 receptor indispensable for signaling by the beta common (βc) family of cytokines encompassing GM-CSF, IL-5 IL-3, which instigate both Type-2 non-Type-2 inflammatory responses. This study aims to determine whether antagonising can prevent pulmonary inflammation, alveolar cell death emphysema development. Methods We performed...
Prostate cancer (PC) is the most common in men. Elevated levels of E3 ligase, E6-Associated Protein (E6AP) were previously linked to PC, consistent with increased protein expression a subset PC patients. In cancers, irregular ligase activity drives proteasomal degradation tumor suppressor proteins. Accordingly, inhibitors define rational therapy restore suppression. The relevant suppressors targeted by E6AP are yet be fully identified. this study we show that p27, key cell cycle regulator,...
Introduction The development of radioresistance in prostate cancer (PCa) is an important clinical issue and still largely uninformed by personalized molecular characteristics. aim this study was to establish a platform that describes the early oncoproteomic response human tissue radiation therapy (RT) using prospective cohort. Methods Fresh fixed transperineal biopsies from eight men with clinically localized tumors were taken prior 14 days following single fraction high‐dose‐rate...
E6AP exhibits tumor suppressor activity that may help stratify NSCLC patients.
Abstract Activation of p38 MAPK has been shown to be relevant for a number bone morphogenetic protein (BMP) physiological effects. We report here the involvement noncanonical phosphorylated mothers against decapentaplegic (Smad) signaling in transcriptional induction Cox2 (Ptgs2) by BMP-2 mesenchymal cells and organotypic calvarial cultures. demonstrate that different regulatory elements are required regulation expression BMP-2: Runt-related transcription factor-2 cAMP response element sites...
Drug resistance is a major obstacle for the successful treatment of many malignancies, including neuroblastoma, most common extracranial solid tumor in childhood. Therefore, current attempts to improve survival neuroblastoma patients, as well those with other cancers, largely depend on strategies counter cancer cell drug resistance; hence, it critical understand molecular mechanisms that mediate chemotherapeutics. The levels LIM-kinase 2 (LIMK2) are increased cells selected their...
Recently, we showed that the ubiquitin ligase E6AP stabilizes β-catenin and activates its transcriptional activity. These activities were enhanced by human papillomavirus (HPV) E6 protein. In present study, explored function of E6AP, which increases stabilization activation. Here, report interacts with mediates nonproteolytic ubiquitylation, as evidenced in transiently transfected cell-based vitro reconstitution ubiquitylation assays. Overexpression increased polyubiquitylation and,...
Systemic lupus erythematosus (SLE) is an autoimmune disease with significant morbidity and mortality. Type I interferon (IFN) drives SLE pathology plasmacytoid dendritic cells (pDCs) are potent producers of IFN; however, the specific effects pDC depletion have not been demonstrated. We show CD123 was highly expressed on pDCs anti-CD123 antibody CSL362 potently depleted
Abstract Objectives Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS associated with significant morbidity and mortality, but its pathogenesis remains incompletely understood, as result, biomarkers are lacking treatment expectant supportive. This study aimed to understand the pathophysiological mechanisms driving induced by CPB identify novel therapeutic targets that might reduce systemic inflammation improve patient outcomes....
Prostate cancer is a common cause of cancer-related death in men. E6AP (E6-Associated Protein), an E3 ubiquitin ligase and transcription cofactor, elevated subset prostate patients. Genetic manipulations cells expose role promoting growth survival vitro vivo However, the effect on broad it cannot be explained fully by previously identified tumor suppressor targets E6AP, promyelocytic leukemia protein p27. To explore additional players that are regulated downstream we combined transcriptomic...
Although primary prostate cancer is largely curable, progression to metastatic disease associated with very poor prognosis. E6AP an E3 ubiquitin ligase and a transcriptional co-factor involved in normal development. drives when overexpressed. Our study exposed role for the promotion of phenotype cells. We revealed that elevated levels correlate regional metastasis demonstrated promotes acquisition mesenchymal features, migration potential, ability anchorage-independent growth. identified...