A5061871732- DNA Repair Mechanisms
- Cancer-related gene regulation
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Wnt/β-catenin signaling in development and cancer
- Nuclear Structure and Function
- Liver Disease Diagnosis and Treatment
- Immune Cell Function and Interaction
- Cancer, Lipids, and Metabolism
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- Cancer Immunotherapy and Biomarkers
- Liver physiology and pathology
- Microtubule and mitosis dynamics
- Immunotherapy and Immune Responses
- Parasitic Infections and Diagnostics
- Immune cells in cancer
- Carbohydrate Chemistry and Synthesis
- TGF-β signaling in diseases
- Glycosylation and Glycoproteins Research
- Skin and Cellular Biology Research
University of Malaya
2024
Chinese University of Hong Kong
2012-2022
University of Hong Kong
2019
The University of Sydney
2007-2016
Westmead Institute for Medical Research
2015-2016
Chinese University of Hong Kong, Shenzhen
2014-2016
Westmead Hospital
2007-2013
Westmead Institute
2007-2013
UNSW Sydney
2005-2008
Howard Hughes Medical Institute
1993
Hepatocellular carcinoma (HCC), mostly developed in fibrotic/cirrhotic liver, exhibits relatively low responsiveness to immune checkpoint blockade (ICB) therapy. As myeloid-derived suppressor cell (MDSC) is pivotal for immunosuppression, we investigated its role and regulation the fibrotic microenvironment with an aim of developing mechanism-based combination immunotherapy.Functional significance MDSCs was evaluated by flow cytometry using two orthotopic HCC models liver setting via carbon...
Hepatocellular carcinomas (HCC) exhibit distinct promoter hypermethylation patterns, but the epigenetic regulation and function of transcriptional enhancers remain unclear. Here, our affinity- bisulfite-based whole-genome sequencing analyses reveal global enhancer hypomethylation in human HCCs. Integrative epigenomic characterization further pinpoints a recurrent hypomethylated CCAAT/enhancer-binding protein-beta (C/EBPβ) which correlates with C/EBPβ over-expression poorer prognosis...
P Li, X He, M R Gerrero, Mok, A Aggarwal, and G Rosenfeld Howard Hughes Medical Institute, University of California, School Medicine, San Diego.
Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men, but molecular mechanism remains obscure. Here, we show that an androgen receptor (AR)-driven oncogene, cell cycle-related kinase (CCRK), collaborates with obesity-induced pro-inflammatory signaling to promote non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Lentivirus-mediated Ccrk ablation liver male mice fed high-fat high-carbohydrate diet abrogates not only obesity-associated lipid...
Many of the DNA sequence variants identified in breast cancer susceptibility gene BRCA1 remain unclassified terms their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance such variants, but comparative value these methods for classifying all has limited.We compared results from with those several analyses four A1708E, G1738R, R1699Q, A1708V.Our show that analysis, which...
Genomic sequencing of hepatocellular carcinoma (HCC) uncovers a paucity actionable mutations, underscoring the necessity to exploit epigenetic vulnerabilities for therapeutics. In HCC, EZH2-mediated H3K27me3 represents major oncogenic chromatin modification, but how it modulates therapeutic vulnerability signaling pathways remains unknown. Here, we show EZH2 acts antagonistically AKT in maintaining H3K27 methylome through silencing IGFBP4. ChIP-seq revealed enrichment Ezh2/H3K27me3 at...
Smad7 is a principal inhibitor of the TGFβ-Smad signalling pathway. We have investigated functional significance in hepatocellular carcinoma (HCC). knockout (KO) and wild-type (WT) mice were injected with diethylnitrosamine (DEN) to induce HCC. The effects on cellular features examined HCC cells, using over-expression or deletion approach. Signalling pathway components modulated by evaluated luciferase reporter assay co-immunoprecipitation. was down-regulated human HCCs compared adjacent...
BackgroundAndrogen receptor (AR) plays a crucial role as transcription factor in promoting the development of hepatocellular carcinoma (HCC) which is prone to aberrant chromatin modifications. However, regulatory effects AR on epigenetic mediators HCC remain ill-defined. Enhancer zeste homolog 2 (EZH2), an oncogene responsible for tri-methylation histone H3 at lysine 27 (H3K27me3), was identified be overexpressed approximate 70–90% cases, prompted us investigate whether or how regulates EZH2...
Hepatocellular carcinoma (HCC) is a worldwide threat to public health, especially in China, where chronic hepatitis B virus (HBV) infection found 80-90% of all HCCs. The HBV-encoded X antigen (HBx) trans-regulatory protein involved virus-induced hepatocarcinogenesis. Although the carboxyl-terminus-truncated HBx, rather than full-length counterpart, frequently overexpressed human HCCs, its functional mechanisms are not fully defined. We investigated molecular function naturally occurring HBx...
The adenomatous polyposis coli (APC) protein tumor suppressor is mutated in the majority of colon cancers. Most APC gene mutations cause deletion C terminus and disrupt regulation β-catenin turnover, microtubule dynamics, chromosome segregation. Truncated mutant peptides may also gain unique properties, not exhibited by wild-type APC, which contribute to cell survival proliferation. Here we report a differential subcellular localization pattern for APC. A pool truncation mutants was detected...
Abstract Mouse mammary tumor virus (MMTV) has long been known as a causal agent of breast cancer in mice. To date, varied MMTV‐like envelope gene ( env ) sequences have identified up to 74% human cancers. However, the role and origin these remain uncertain. Our study was initiated integration cancer. PCR screening 28 (56%) Australian specimens 7 (87.5%) cell lines be positive for sequence. In MCF‐7 genome, fragment containing an sequence ∼1.9 kb plus downstream rodent‐like ∼200 bp found...
The breast cancer associated gene 1 (BRCA1)-A protein complex assembles at DNA damage-induced nuclear foci to facilitate repair of double-stranded breaks. Here, we describe the first systematic comparison dynamics, copy number and organization its core components foci. We show that pools individual generally comprise a small immobile fraction (∼20%) larger mobile (∼80%), which together occupy same focal space but exist different densities. In fraction, Abraxas (CCDC98) heterodimer...