A5031778162- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Fibroblast Growth Factor Research
- Kruppel-like factors research
- bioluminescence and chemiluminescence research
- Radiopharmaceutical Chemistry and Applications
- Microtubule and mitosis dynamics
- Protein Kinase Regulation and GTPase Signaling
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Genomics and Chromatin Dynamics
- Medical Imaging Techniques and Applications
- Melanoma and MAPK Pathways
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Alkaline Phosphatase Research Studies
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
Monash University
2021-2025
Australian Regenerative Medicine Institute
2021-2025
Walter and Eliza Hall Institute of Medical Research
2015-2023
Ludwig Cancer Research
2009-2023
Weatherford College
2023
Olivia Newton-John Cancer Wellness & Research Centre
2014-2022
The University of Melbourne
2005-2021
Austin Hospital
2009-2021
Austin Health
2014-2017
The Royal Melbourne Hospital
2015
We have previously identified and characterized the phenomenon of ectopic human centromeres, known as neocentromeres. Human neocentromeres form epigenetically at euchromatic chromosomal sites are structurally functionally similar to normal centromeres. Recent studies indicated that neocentromere formation provides a major mechanism for centromere repositioning, karyotype evolution, speciation. Using marker chromosome mardel(10) containing formed 10q25 region, we mapped 330-kb CENP-A-binding...
KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate H3K23 exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of to achieve therapeutic benefit has been a challenge. Here we describe identification highly potent, selective, orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from benzisoxazole series, which demonstrates anti-tumor...
Abstract Histone deacetylase inhibitors (HDACi) induce growth arrest and apoptosis in colon cancer cells are being considered for therapy. The underlying mechanism of action these effects is poorly defined with both transcription-dependent -independent mechanisms implicated. We screened a panel 30 cell lines sensitivity to HDACi-induced correlated the differences gene expression patterns induced by HDACi five most sensitive resistant lines. A robust reproducible transcriptional response...
Inhibitors of the bromodomain and extraterminal domain (BET) protein family attenuate proliferation several tumor cell lines. These effects are mediated, at least in part, through repression c-MYC. In colorectal cancer, overexpression c-MYC due to hyperactive WNT/β-catenin/TCF signaling is a key driver progression; however, effective strategies target this oncogene remain elusive. Here, we investigated effect BET inhibitors (BETi) on cancer expression. Treatment 20 lines with BETi JQ1...
Abstract Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in acute myelogenous leukemia, non–small cell lung cancer, estrogen receptor–positive breast trials underway assessing their combination regimens including immunotherapy. However, there is currently no clear strategy to reliably predict HDACi sensitivity. In colon cancer...
Human neocentromeres are fully functional centromeres that arise epigenetically from non-centromeric precursor sequences devoid of α-satellite DNA. Using chromatin immunoprecipitation (ChIP) and BAC-array analysis, we have previously described a 330 kb binding domain for CENP-A (a histone H3 variant confers centromere-specific nucleosomal property) at the 10q25 neocentromere found on chromosome 10-derived marker mardel(10). For further detailed analysis CENP-A-associated chromatin, generated...
// BeeShin Tan 1 , Matthew Anaka Siddhartha Deb 2 Claudia Freyer Lisa M. Ebert 3 Anderly C. Chueh Sheren Al-Obaidi Andreas Behren Aparna Jayachandran Jonathan Cebon Weisan Chen 4 and John Mariadason Ludwig Institute for Cancer Research Ltd. Melbourne-Austin Branch, Heidelberg, Victoria, Australia. Department of Pathology, Peter MacCallum Centre, Melbourne, Centre Biology, SA Frome Road, Adelaide, School Molecular Science, LaTrobe University, Bundoora, Correspondence: Mariadason, email: Chen,...
Abstract Background Point mutations in histone variant H3.3 (H3.3K27M, H3.3G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events pediatric gliomas. These point affect many chromatin modifications but exact oncogenic mechanisms currently unclear. Histone is known to localize nuclear compartments as promyelocytic leukemia (PML) bodies, which frequently mutated confirmed drivers acute leukemia. Results We find that glioma-associated disrupt formation of PML bodies this...
The metabolism of cancer cells is often reprogrammed by dysregulation metabolic enzymes. Transketolase-like 1 (TKTL1) a homodimeric transketolase linking the pentose-phosphate pathway with glycolytic pathway. It generally silenced at transcriptional level in somatic tissues. However, human cancers its expression associated acquisition phenotype (the Warburg effect) that contributes to progression malignant tumors. In melanoma, defective promoter methylation results genes and their products...
Abstract The phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort examine whether single nucleotide polymorphisms (SNPs) VEGF-A , VEGFR1 and VEGFR2 are predictive of efficacy outcomes development hypertension. Genomic DNA extracted from archival FFPE tissue for 325 (69% population) was used genotype 16...
Oncogenic FGFR4 signaling represents a potential therapeutic target in various cancer types, including triple-negative breast and hepatocellular carcinoma. However, resistance to single-agent therapy remains major challenge, emphasizing the need for effective combinatorial treatments. Our study sought develop comprehensive computational model of provide network-level insights into mechanisms driven by dynamics. An integrated approach, combining network modeling with experimental validation,...
Reciprocal interactions between prostate cancer cells and carcinoma-associated fibroblasts (CAFs) mediate development progression; however, our understanding of the signalling pathways mediating these cellular remains incomplete. To address this, we defined secretome changes upon co-culture epithelial or with that mimic bi-directional communication in tumours. Using antibody arrays, profiled conditioned media from mono- co-cultures fibroblasts, cells, identifying secreted proteins are...
We have previously identified and characterized the phenomenon of ectopic human centromeres, known as neocentromeres.Human neocentromeres form epigenetically at euchromatic chromosomal sites are structurally functionally similar to normal centromeres.Recent studies indicated that neocentromere formation provides a major mechanism for centromere repositioning, karyotype evolution, speciation.Using marker chromosome mardel(10) containing formed 10q25 region, we mapped 330-kb CENP-A-binding...
CS-1008 (tigatuzumab; phase I/II), an antihuman death receptor 5 (DR5) agonist, induces apoptosis and has cytotoxic activity against human cancer cell lines. This study reports on the preclinical validation of (111)In-labeled anti-DR5 humanized antibody as a diagnostic tool to DR5 occupancy in patients with establish dose ranges for saturation kinetics vivo.CS-1008 was radiolabeled characterized binding labeling efficiency TRAIL-sensitive DR5-positive colorectal cells (COLO 205 WiDr)....
The introduction of molecular techniques in conjunction with classical cytogenetic methods has recent years greatly improved the diagnostic potential for chromosomal abnormalities. In particular, microarray–comparative genomic hybridization (CGH) based on use BAC clones promises a sensitive strategy detection DNA copy-number changes genomewide scale, offering resolution as high >30,000 “bands” (as defined by number BACs within currently highest-density array) [Ishkanian et al., 2004]. We...
Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but aberrant in up 30% of non-small cell lung cancers (NSCLCs). Regulation CTA is mediated part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms NSCLC. Given its immunogenicity and ability be re-expressed demethylation, NY-ESO-1 methylation, protein association programmed death receptor ligand-1 (PD-L1) clinicopathological features were...
C-terminal Src kinase (Csk) and Csk-homologous (Chk) are the major endogenous inhibitors of Src-family kinases (SFKs). They employ two mechanisms to inhibit SFKs. First, they phosphorylate tail tyrosine which stabilizes SFKs in a closed inactive conformation by engaging SH2 domain cis. Second, non-catalytic inhibitory mechanism involving direct binding Csk Chk active forms that is independent phosphorylation their tail. co-expressed many cell types. Contributions towards activity not fully...
The ERK signalling pathway regulates key cell fate decisions in the intestinal epithelium and is frequently dysregulated colorectal cancers (CRCs). Variations dynamics of activation can induce different biological outcomes are regulated by multiple mechanisms, including negative feedback loops involving transcriptional induction dual-specificity phosphatases (DUSPs). We have found that nuclear ERK-selective phosphatase DUSP5 downregulated tumours lines, as previously observed gastric...