A5055936733- Helicobacter pylori-related gastroenterology studies
- Fibroblast Growth Factor Research
- Metastasis and carcinoma case studies
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
- Barrier Structure and Function Studies
- Cancer Mechanisms and Therapy
- Wnt/β-catenin signaling in development and cancer
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Gastric Cancer Management and Outcomes
- Cancer-related gene regulation
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Digestive system and related health
- IL-33, ST2, and ILC Pathways
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Kruppel-like factors research
- Neurological Disease Mechanisms and Treatments
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
La Trobe University
2016-2025
Olivia Newton-John Cancer Wellness & Research Centre
2016-2025
Acandis (Germany)
2021
Heidelberg University
2019
Walter and Eliza Hall Institute of Medical Research
2013-2015
Ludwig Cancer Research
2008-2015
The University of Melbourne
2005-2015
AstraZeneca (United States)
2014
The Royal Melbourne Hospital
2000-2011
Institut de Génomique Fonctionnelle
2006-2010
Deregulated activation of STAT3 is frequently associated with many human hematological and epithelial malignancies, including gastric cancer. While exaggerated signaling facilitates an antiapoptotic, proangiogenic, proproliferative environment for neoplastic cells, the molecular mechanisms leading to hyperactivation remain poorly understood. Using gp130Y757F/Y757F mouse model cancer, which carries a mutated gp130 cytokine receptor subunit that cannot bind negative regulator SOCS3...
Abstract The contribution of mast cells in the microenvironment solid malignancies remains controversial. Here we functionally assess impact tumor-adjacent, submucosal cell accumulation murine and human intestinal-type gastric cancer. We find that genetic ablation or therapeutic inactivation suppresses tumor-associated macrophages, reduces tumor proliferation angiogenesis, diminishes burden. Mast are activated by interleukin (IL)-33, an alarmin produced epithelium response to inflammatory...
The AF-6/afadin protein, which contains a single PDZ domain, forms peripheral component of cell membranes at specialized sites cell-cell junctions. To identify potential receptor-binding targets AF-6 we screened the domain against range COOH-terminal peptides selected from receptors having domain-binding termini. interacts with subset members Eph subfamily RTKs via its COOH terminus both in vitro and vivo. Cotransfection green fluorescent protein-tagged fusion protein full-length into...
Gastrointestinal cancers are frequently associated with chronic inflammation and excessive secretion of IL-6 family cytokines, which promote tumorigenesis through persistent activation the GP130/JAK/STAT3 pathway. Although tumor progression can be prevented by genetic ablation Stat3 in mice, this transcription factor remains a challenging therapeutic target paucity clinically approved inhibitors. Here, we uncovered parallel mTOR complex 1 (mTORC1) alongside STAT3 human intestinal-type...
Abstract Tight junctions have recently emerged as essential signaling regulators of proliferation and differentiation in epithelial tissues. Here, we aimed to identify the factors regulating claudin-7 expression colon, analyzed consequences overexpression colorectal carcinoma (CRC). In healthy human colonic crypts, was found be low stem/progenitor cell compartment, where Tcf-4 activity is high, but strong differentiated postmitotic cells, inactive. contrast, overexpressed areas with high...
Contributions of null and hypomorphic alleles Apc in mice produce both developmental pathophysiological phenotypes. To ascribe the resulting genotype-to-phenotype relationship unambiguously to Wnt/β-catenin pathway, we challenged allele combinations by genetically restricting intracellular β-catenin expression corresponding compound mutant mice. Subsequent evaluation extent Tcf4-reporter activity mouse embryo fibroblasts enabled genetic measurement signaling form an allelic series mutants....
Partial suppression of the inflammatory gp130-Jak-Stat pathway inhibits intestinal tumor growth.
Autophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show epithelium-specific deletion in adult mice leads to rapid fatal enteritis compromised gut barrier integrity, highlighting its intrinsic critical role maintenance. BECLIN1-deficient epithelial cells exhibit extensive apoptosis, impaired autophagy, stressed...
Symplekin is a ubiquitously expressed protein involved in cytoplasmic RNA polyadenylation and transcriptional regulation localized at tight junctions (TJs) epithelial cells. Nuclear symplekin cooperates with the Y-box transcription factor zonula occludens 1-associated nucleic acid-binding (ZONAB) to increase of cell cycle-related genes also inhibits differentiation intestinal We detected high levels nuclear 8 12 human colorectal cancer (CRC) samples. shRNA-mediated reduction expression was...
ADP-ribosylation is an important posttranslational protein modification that regulates diverse biological processes, controlled by dedicated transferases and hydrolases. Here, we show frequent deletions (∼30%) of the
The novel coronavirus disease 2019 (COVID-19) is considered to be a significant health challenge worldwide because of its rapid human-to-human transmission, leading rise in the number infected people and deaths. detection COVID-19 at earliest stage therefore paramount importance for controlling pandemic spread reducing mortality rate. real-time reverse transcription-polymerase chain reaction, primary method diagnosis infection, has relatively high false negative rate while detecting early...
MicroRNA-21 (miR-21) is a small, non-coding RNA overexpressed in gastric cancer and many other solid malignancies, where it exhibits both pro-and anti-tumourigenic properties. However, the pathways regulating miR-21 consequences of its inhibition remain incompletely understood. By exploiting spontaneous Stat3-dependent formation inflammation-associated tumors Gp130F/F mice, we functionally established as Stat3-controlled driver tumor growth progression. We reconciled our discoveries by...
Abstract Although gastric cancer is a leading cause of cancer-related deaths, systemic treatment strategies remain scarce. Here, we report the pro-tumorigenic properties crosstalk between intestinal tuft cells and type 2 innate lymphoid (ILC2) that evolutionarily optimized for epithelial remodeling in response to helminth infection. We demonstrate cell-derived interleukin 25 (IL25) drives ILC2 activation, inducing release IL13 promoting cell hyperplasia. While resulting - feed-forward...
The expression pattern of tight junction (TJ) proteins is frequently disrupted in epithelial tumors. In particular, isoform- and organ-specific alterations claudins have been detected human cancers, highlighting them as interesting tools for the prognosis or treatment various carcinomas. However, molecular mechanisms responsible these are seldom identified. Here, we analyzed localization 1, 4, 7 bladder carcinoma. Claudin-4 was significantly altered 26/39 tumors, contrasting with rare...
Epithelial tight junctions participate in the regulation of gene expression by controlling activity transcription factors that can interact with junctional components. One such protein is Y-box factor ZONAB/DbpA binds to ZO-1, a component plaque. Symplekin, another nuclear associate junctions, functions polyadenylation and thereby promotes expression. Here, we addressed question whether these two proteins this functional relevance. We demonstrate symplekin form complex kidney intestinal...
Research Article18 March 2019Open Access Source DataTransparent process Repurposing the selective estrogen receptor modulator bazedoxifene to suppress gastrointestinal cancer growth Pathum Thilakasiri Olivia Newton-John Cancer Institute, School of Medicine, La Trobe University, Heidelberg, Vic., Australia Search for more papers by this author Jennifer Huynh Ashleigh R Poh Chin Wee Tan The Walter and Eliza Hall Melbourne, Tracy L Nero ACRF Rational Drug Discovery Centre, St Vincent's...