A5051615423- Sirtuins and Resveratrol in Medicine
- Extracellular vesicles in disease
- FOXO transcription factor regulation
- PARP inhibition in cancer therapy
- Nanoplatforms for cancer theranostics
- Cancer, Lipids, and Metabolism
- Genomics, phytochemicals, and oxidative stress
- Adipose Tissue and Metabolism
- interferon and immune responses
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Genetic factors in colorectal cancer
- MicroRNA in disease regulation
- Cell death mechanisms and regulation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Redox biology and oxidative stress
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Circular RNAs in diseases
- Mast cells and histamine
- Genetics, Aging, and Longevity in Model Organisms
- Antioxidant Activity and Oxidative Stress
- Ubiquitin and proteasome pathways
- Aldose Reductase and Taurine
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
The University of Sydney
2022-2024
University School
2023
Zhongshan Hospital
2023
Fudan University
2023
Harry Perkins Institute of Medical Research
2023
Hammersmith Hospital
2018-2021
Imperial College London
2018-2021
Medical Research Council
2019
MRC Laboratory for Molecular Cell Biology
2019
University College London
2019
Forkhead Box O3 (FOXO3) is a tumor suppressor whose activity fine-tuned by post-translational modifications (PTMs). In this study, using the BT474 breast cancer cells and recently established lapatinib resistant (BT474-LapR) cell line, we observed that higher FOXO3 acetylated (Ac)-FOXO3 levels correlate with sensitivity. Subsequent ectopic expression of EP300 led to an increase in acetylated-FOXO3 sensitive but not cells. Drug sensitivity assays revealed show increased cytotoxicity upon...
A recently-discovered protein post-translational modification, lysine polyphosphorylation (K-PPn), consists of the covalent attachment inorganic polyphosphate (polyP) to residues. The nonenzymatic nature K-PPn means that degree this modification depends on both polyP abundance and amino acids surrounding modified lysine. was originally discovered in budding yeast (
The major impediment to effective cancer therapy has been the development of drug resistance. tumour suppressive transcription factor FOXO3 promotes cell cycle arrest, senescence and death, mediates cytotoxic cytostatic functions therapeutics. In consequence, is often downregulated as an adaptive response in particularly chemotherapeutic drug-resistant cells. Consistently, we find that expression attenuated MCF-7-EpiR MCF-7-TaxR compared parental MCF-7 breast Using ChIP, short-interfering...
The cellular response to hypoxia is regulated through enzymatic oxygen sensors, including the prolyl hydroxylases, which control degradation of well-known inducible factors (HIFs). Other sensors have been recently identified, members KDM histone demethylase family. Little known about how different oxygen-sensing pathways interact and if this varies depending on form hypoxia, such as chronic or intermittent. In study, we investigated two proposed systems, HIF-1 KDM4A, KDM4B, KDM4C, respond in...
Abstract Estrogen-related receptor beta (ERRβ) is downregulated in breast cancer cells and its overexpression patients positively correlated with an improved prognosis prolonged relapse-free survival. Here, we unravelled a molecular mechanism for ERRβ downregulation cancer. We found that key substrate of the SCF complex NEDDylation can activate Cullin subunits to target degradation Consistently, using vitro vivo models, demonstrated MLN4924, specific small molecule inhibitor NEDDylation,...
Abstract Fluorouracil (5-FU) is the first-line chemotherapeutic drug for cholangiocarcinoma (CCA), but its efficacy has been compromised by development of resistance. Development 5-FU resistance associated with elevated expression cellular target, thymidylate synthase (TYMS). E2F1 transcription factor previously shown to modulate FOXM1 and TYMS. Immunohistochemical (IHC) analysis revealed a strong correlated upregulation (78%) TYMS (48%) at protein levels in CCA tissues. In agreement,...
A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many these compounds feature electrophilic functionalities that potentially undergo covalent addition the sulfhydryl side chain cysteine residues within proteins. However, impact such modifications on platelet activity function remains unclear. This study explores irreversible engagement 23 with platelets, unveiling unique antiplatelet selectivity sulforaphane (SFN). SFN...
Abstract Background Chemoresistance is an obstacle to the successful treatment of nasopharyngeal carcinoma (NPC). Lapatinib a targeted tyrosine kinase inhibitor therapeutic drug also used treat NPC, but high doses are often required achieve result. To investigate mechanism for development resistance, we characterised number NPC cell lines determine role FOXO3 and sirtuins in regulating resistance. Methods Sulforhodamine B (SRB) assays, Clonogenic Protein extraction, quantification western...
Pharmaceutical inhibitors of the endoplasmic reticulum (ER)-stress modulator PERK (eIF2AK3) have demonstrated anticancer activities in combination therapies, but their effectiveness as a single agent is limited, suggesting existence possible compensatory cellular responses. To explore potential mechanisms involved, we performed time-course drug treatment experiments on parental MCF-7 and resistant MCF-7EpiR MCF-7TaxR breast cancer cells identified GCN2 (eIF2AK4) molecule that can potentially...
ABSTRACT Cellular senescence is a potent tumor-suppressive program that prevents neoplastic events. Paradoxically, senescent cells develop an inflammatory secretome, termed the senescence-associated secretory phenotype (SASP) and implicated in age-related pathologies including cancer. Here we report actively synthesize release small extracellular vesicles (sEVs) with distinctive size distribution. Mechanistically, SIRT1 loss supports accelerated sEV production despite enhanced proteome-wide...
A large variety of dietary phytochemicals have been shown to improve thrombosis and stroke outcomes in preclinical studies. Many these compounds feature electrophilic functionalities that potentially undergo covalent addition the sulfhydryl side chain cysteine residues within proteins. However, impact such modifications on platelet activity function remains unclear. In this study, we evaluated phenotypes associated with irreversible protein engagement twenty-three phytochemicals. This...
Abstract Background Chemoresistance is an obstacle to the successful treatment of nasopharyngeal carcinoma (NPC). Lapatinib a targeted tyrosine kinase inhibitor therapeutic drug also used treat NPC, but high doses are often required achieve result. To investigate mechanism for development resistance, we characterised number NPC cell lines determine role FOXO3 and sirtuins in regulating resistance. Methods Sulforhodamine B (SRB) assays, Clonogenic Protein extraction, quantification western...
<p>Antibody information summary.</p>
<p>Clinical, pathological, cell biology and bioinformatics-based experimental protocols.</p>
<p>Figure S1. Cellular senescence, expression profiling and the SASP development in human stromal cells upon genotoxic treatment. Figure S2. SIRT1 decline is not related with single strand breaks, proteasome degradation or autophagy deficiency cellular senescence. S3. Senescent sEVs enhance malignancy of prostate cancer cells. S4. Transcriptomic exposure to senescent establishment protein-protein interaction network involving ABCB4. S5. sEV-conferred diminished elimination ABCB4 from...
<p>Figure S1. Cellular senescence, expression profiling and the SASP development in human stromal cells upon genotoxic treatment. Figure S2. SIRT1 decline is not related with single strand breaks, proteasome degradation or autophagy deficiency cellular senescence. S3. Senescent sEVs enhance malignancy of prostate cancer cells. S4. Transcriptomic exposure to senescent establishment protein-protein interaction network involving ABCB4. S5. sEV-conferred diminished elimination ABCB4 from...
<div>Abstract<p>Cellular senescence is a potent tumor-suppressive program that prevents neoplastic events. Paradoxically, senescent cells develop an inflammatory secretome, termed the senescence-associated secretory phenotype, which implicated in age-related pathologies including cancer. Here, we report actively synthesize and release small extracellular vesicles (sEV) with distinctive size distribution. Mechanistically, SIRT1 loss supported accelerated sEV production despite...
<p>Functional enrichments in PPT network.</p>
<p>Primer information summary.</p>
<p>Functional enrichments in PPT network.</p>