A5001199681- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Pancreatic function and diabetes
- Cancer Mechanisms and Therapy
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Immune Cell Function and Interaction
- Skin Protection and Aging
- Peptidase Inhibition and Analysis
- Erythrocyte Function and Pathophysiology
- Cancer-related Molecular Pathways
- T-cell and B-cell Immunology
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Acne and Rosacea Treatments and Effects
- Wound Healing and Treatments
- Skin and Cellular Biology Research
- Dermatologic Treatments and Research
- Protein Structure and Dynamics
- Genomics and Rare Diseases
- Autoimmune Bullous Skin Diseases
- Immunotherapy and Immune Responses
- Dermatology and Skin Diseases
The University of Melbourne
2016-2025
La Trobe University
2016-2025
Peter MacCallum Cancer Centre
2012-2023
Cancer Genetics (United States)
2010-2018
Université de franche-comté
2009-2018
Centre Hospitalier Universitaire de Besançon
2007-2018
Melbourne Clinic
2018
Inserm
1986-2017
Université Bourgogne Franche-Comté
2017
Goethe University Frankfurt
2015
E2F is a family of transcription factors that regulate both cellular proliferation and differentiation. To establish the role E2F3 in vivo, we generated an E2f3 mutant mouse strain. E2F3-deficient mice arise at one-quarter expected frequency, demonstrating important for normal development. determine molecular consequences deficiency, analyzed properties embryonic fibroblasts derived from mice. Mutation dramatically impairs mitogen-induced, transcriptional activation numerous E2F-responsive...
Loss of cellular polarity is a hallmark epithelial cancers, raising the possibility that regulators have role in suppressing tumorigenesis. The Scribble complex one at least three interacting protein complexes critical establishing and maintaining polarity. In human colorectal, breast, endometrial expression member SCRIB often mislocalized deregulated. Here, we report Scrib indispensable for prostate homeostasis mice. heterozygosity initiated hyperplasia, while targeted biallelic loss...
The therapeutic efficacy of two bis(thiosemicarbazonato) copper complexes, glyoxalbis[N4-methylthiosemicarbazonato]CuII [CuII(gtsm)] and diacetylbis[N4-methylthiosemicarbazonato]CuII [CuII(atsm)], for the treatment prostate cancer was assessed in cell culture animal models. Distinctively, dissociates intracellularly from CuII(gtsm) but is retained by CuII(atsm). We further demonstrated that intracellular H2gtsm [reduced CuII(gtsm)] continues to redistribute into a bioavailable (exchangeable)...
Anti-cancer drug development involves enormous expenditure and risk. For rapid economical identification of novel, bioavailable anti-tumour chemicals, the use appropriate in vivo tumour models suitable for large-scale screening is key. Using a Drosophila Ras-driven model, we demonstrate that overgrowth can be curtailed by feeding larvae with chemicals have pharmacokinetics essential known efficacy against human cells. We then develop an 96-well plate chemical platform to carry out model. In...
Abstract Genetic alterations that potentiate PI3K signaling are frequent in prostate cancer, yet how different genetic drivers of the cascade contribute to cancer is unclear. Here, we report PIK3CA mutation/amplification correlates with poor survival patients cancer. To interrogate requirement employed a approach mutate Pik3ca mouse epithelium. We show Pik3caH1047R mutation causes p110α-dependent invasive carcinoma vivo. Furthermore, and PTEN loss coexist can cooperate vivo accelerate...
Asymmetric cell division is a potential means by which fate choices during an immune response are orchestrated. Defining the molecular mechanisms that underlie asymmetric of T cells paramount for determining role this process in generation effector and memory subsets. In other types, regulated conserved polarity protein complexes control localization determinants spindle orientation division. We have developed tractable, vitro model naive CD8(+) undergoing initial while attached to dendritic...
The crucial role the Crumbs and Par polarity complexes play in tight junction integrity has long been established, however very few studies have investigated of Scribble module. Here we use MCF10A cells, which fail to form junctions express little endogenous Crumbs3, show that inducing expression protein is sufficient promote formation. We this occurs through an epithelial mesenchymal (EMT) pathway involves suppressing ERK phosphorylation, leading down regulation EMT inducer ZEB. Inhibition...
We have shown previously that mutations in the apico-basal cell polarity regulators cooperate with oncogenic Ras (Ras(ACT)) to promote tumorigenesis Drosophila melanogaster and mammalian cells. To identify novel genes Ras(ACT) tumorigenesis, we carried out a genome-wide screen for when overexpressed throughout developing eye enhance Ras(ACT)-driven hyperplasia. Ras(ACT)-cooperating identified were Rac1 Rho1, RhoGEF2, pbl, rib, east, which encode morphology regulators. In clonal setting,...
In metazoans, Bcl-2 family proteins are major regulators of mitochondrially mediated apoptosis; however, their evolution remains poorly understood. Here, we describe the molecular characterization four members in most primitive metazoan, Trichoplax adhaerens All trBcl-2 homologs multimotif group, with trBcl-2L1 and trBcl-2L2 being highly divergent antiapoptotic members, whereas trBcl-2L3 trBcl-2L4 proapoptotic Bax Bak, respectively. trBax expression permeabilizes mitochondrial outer...
Abstract SARS-CoV-2 infection leads to coronavirus disease 2019 (COVID-19), which is associated with severe and life-threatening pneumonia respiratory failure. However, the molecular basis of these symptoms remains unclear. SARS-CoV-1 E protein interferes control cell polarity cell-cell junction integrity in human epithelial cells by binding PALS1 PDZ domain, a key component Crumbs complex. We show that C-terminal motifs proteins bind domain 29.6 22.8 μM affinity, whereas related sequence...
The tumor-suppressor PTPN2 is diminished in a subset of triple-negative breast cancers (TNBCs). Paradoxically, PTPN2-deficiency tumors or T cells mice can facilitate cell recruitment and/or activation to promote antitumor immunity. Here, we explored the therapeutic potential targeting tumor and cells. TNBC associated with infiltrates PD-L1 expression, whereas low improved survival. deletion murine mammary epithelial models, did not tumorigenicity but increased STAT-1–dependent expression...