A5045827195- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Cancer-related molecular mechanisms research
- Mycobacterium research and diagnosis
- Helicobacter pylori-related gastroenterology studies
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Eosinophilic Esophagitis
- RNA Research and Splicing
- Cancer Immunotherapy and Biomarkers
- RNA and protein synthesis mechanisms
- Digestive system and related health
- Cancer-related gene regulation
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Gastric Cancer Management and Outcomes
- Whipple's Disease and Interleukins
- Crystallization and Solubility Studies
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
- Ferrocene Chemistry and Applications
- Circular RNAs in diseases
Olivia Newton-John Cancer Wellness & Research Centre
2016-2025
La Trobe University
2015-2025
Paul Ehrlich Institut
2023-2024
Hospital for Special Surgery
2024
University of Illinois Urbana-Champaign
2024
Cornell University
2024
New York Hospital Queens
2024
NewYork–Presbyterian Hospital
2024
Hokkaido University
2024
Walter and Eliza Hall Institute of Medical Research
2014-2015
Abstract The long noncoding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), also known as MALAT-1 or NEAT2 (nuclear-enriched abundant 2), is a highly conserved nuclear (ncRNA) and predictive marker for metastasis development in cancer. To uncover its functional importance, we developed knockout model human tumor cells by genomically integrating destabilizing elements using zinc finger nucleases. achieved 1,000-fold silencing provides unique loss-of-function model....
The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as marker for cancer metastasis. It highly abundant, its expression strongly regulated in many tumor entities including and hepatocellular carcinoma well physiological processes, it associated with binding proteins conserved throughout evolution. nuclear MALAT-1 functionally gene regulation alternative splicing shown to impact proliferation, apoptosis, migration...
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...
Partial suppression of the inflammatory gp130-Jak-Stat pathway inhibits intestinal tumor growth.
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...
As a contribution to bioorganometallic chemistry, an enantioselective synthesis of novel carbocyclic nucleoside analogues with ferroceno-cyclopentene backbone was developed. Diastereoselective cuprate 1,4-addition or Mukaiyama−Michael addition planar-chiral enoate (ethyl (E)-2-[2-methoxycarbonyl-ferrocenyl]-acrylate) allowed for the introduction different side chains (RCH2). Other important steps include Dieckmann cyclization and attachment nucleobase (NB) in iron-assisted SN1 reaction. Some...
Abstract IL11 is a member of the IL6 family cytokines and signals through its cognate receptor subunits, IL11RA glycoprotein 130 (GP130), to elicit biological responses via JAK/STAT signaling pathway. contributes cancer progression by promoting survival proliferation cells, but potential immunomodulatory properties during tumor development have thus far remained unexplored. Here, we characterized role for in regulating CD4+ T cell–mediated antitumor responses. Absence impaired growth...
Abstract About 5% to 10% of human gastric tumors harbor oncogenic mutations in the KRAS pathway, but their presence alone is often insufficient for inducing tumorigenesis, suggesting a requirement additional mutagenic events or microenvironmental stimuli, including inflammation. Assessing contribution such preclinical mouse models requires Cre recombinase–mediated conditional gene expression stem progenitor cells normal and transformed epithelium. We therefore constructed bacterial...
Abstract Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts IL33 its receptor St2. therefore continuously homeostatic turnover intestinal mucosa. Although can prevent colon cancer associated with colitis, contribution signaling to sporadic remains unknown. Here, we utilized a mouse model investigate tumorigenesis in absence preexisting inflammation. We demonstrated that genetic ablation St2...
Abstract Persistent activation of the latent transcription factor STAT3 is observed in gastric tumor epithelial and immune cells associated with a poor patient prognosis. Although targeting STAT3-activating upstream kinases offers therapeutically viable targets limited specificity, direct inhibition remains challenging. Here we provide functional evidence that myeloid-specific hematopoietic cell kinase (HCK) activity can drive STAT3-dependent growth mice alternative macrophage alongside...
Although aberrant activation of the KRAS and PI3K pathway alongside TP53 mutations account for frequent aberrations in human gastric cancers, neither sequence nor individual contributions these have been clarified. Here, we establish an allelic series mice to afford conditional expression glandular epithelium Kras
Revising public health policy based on new data does not happen automatically. This is acutely relevant to the now undeniable evidence that many diseases develop differently between sexes and may also be affected by gender. Current medical practices across globe generally fail cater for sex gender effects in common diseases. Inadequate frameworks guide comprehensive inclusion of research jeopardises scientific rigour ultimately they underpin. To ensure Australian fit-for-purpose, we realised...
Gene-of-interest knockout organoids present a powerful and versatile research tool to study gene's effects on many biological pathological processes. Here, we straightforward broadly applicable protocol generate gene knockouts in mouse using CRISPR-Cas9 technology. We describe the processes of transient transfecting with pre-assembled ribonucleoprotein complexes, organoid cell sorting, establishing clonal culture pairs. then detail how confirm via Western blot analysis.
Doublecortin-like kinase 1 (DCLK1) is a proposed driver of gastric cancer (GC) that phosphorylates serine and threonine residues. Here, we showed the activity DCLK1 orchestrated cell-intrinsic and-extrinsic processes led to pro-invasive pro-metastatic reprogramming GC cells. Inhibition reduced growth subcutaneous xenograft tumors formed from MKN1 human carcinoma cells in mice decreased abundance stromal markers α-Sma, vimentin, collagen. Similar effects were seen with expressing...
Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification many cell death-repressing cDNAs, including 28% are already known inhibit apoptosis, 35% upregulated at least one...
ABSTRACT Ets homologous factor (EHF) is a member of the epithelial-specific (ESE) family transcription factors. To investigate its role in development and epithelial homeostasis, we generated series novel mouse strains which DNA-binding domain Ehf was deleted all tissues (Ehf−/−) or specifically gut epithelium. Ehf−/− mice were born at expected Mendelian ratio, but showed reduced body weight gain, developed pathologies requiring most to reach an ethical endpoint before reaching 1 year age....
Activation of the Wnt/β-catenin pathway occurs in a vast majority colorectal cancers. However, outcome disease strongly varies from patient to patient, even within same tumor stage. This heterogeneity is governed large parts by genetic makeup individual tumors and combination oncogenic mutations. To express throughout intestinal epithelium degradation resistant β-catenin (Ctnnb1) which lacks first 131 amino acids, we inserted an epitope-tagged ΔN(1-131)-β-catenin encoding cDNA as knockin...
Abstract Although gastric cancer is a leading cause of cancer-related deaths, systemic treatment strategies remain scarce. Here we explore metabolite-triggered circuit between epithelial tuft cells and innate lymphoid type 2 (ILC2) that evolutionarily optimized for intestinal remodeling in response to helminth infection. We demonstrate cell-derived interleukin 25 (IL25) acts as an alarmin on ILC2s induce the release IL13 growth factor cells, propose this model drives early metaplastic tumor...
Abstract Signal transducer and activator of transcription 3 (Stat3) is a factor that has many essential roles during inflammation, development cancer. Stat3 therefore an attractive therapeutic target in diseases. While current knockout mouse models led to better understanding the role Stat3, irreversible nature ablation does not model effects transient inhibition, inform on potential dosage Stat3. Using RNAi technology, we have generated new allowing inducible reversible silencing vivo ,...
Temporal and spatial regulation of genes mediated by tissue-specific promoters conditional gene expression systems provide a powerful tool to study function in health, disease, during development. Although transgenic mice expressing the Cre recombinase gastric epithelium have been reported, there is lack models that allow inducible reversible modification stomach. Here, we exploited gastrointestinal epithelium-specific pattern three trefoil factor (Tff) bacterial artificial chromosome...