A5061301662- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- Ubiquitin and proteasome pathways
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
- RNA Research and Splicing
- Cancer-related gene regulation
- Glioma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Telomeres, Telomerase, and Senescence
- Genomics and Chromatin Dynamics
- ATP Synthase and ATPases Research
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
Agency for Science, Technology and Research
2017-2024
Genome Institute of Singapore
2017-2022
Chemo-resistance is one of the major causes cancer-related deaths. Here we used single-cell transcriptomics to investigate divergent modes chemo-resistance in tumor cells. We observed that higher degree phenotypic intra-tumor heterogeneity (ITH) favors selection pre-existing drug-resistant cells, whereas phenotypically homogeneous cells engage covert epigenetic mechanisms trans-differentiate under drug-selection. This adaptation was driven by selection-induced gain H3K27ac marks on...
Genomics-driven cancer therapeutics has gained prominence in personalized treatment. However, its utility indications lacking biomarker-driven treatment strategies remains limited. Here we present a "phenotype-driven precision-oncology" approach, based on the notion that biological response to perturbations, chemical or genetic, ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic clinic. We generated library of "screenable" patient-derived primary...
Abstract Gain of function (GOF) DNA binding domain (DBD) mutations TP53 upregulate chromatin regulatory genes that promote genome-wide histone methylation and acetylation. Here, we therapeutically exploit the oncogenic GOF mechanisms p53 codon 158 (Arg ) mutation, a DBD mutant found to be prevalent in lung carcinomas. Using high throughput compound screening combination analyses, uncover acetylating mutp53 R158G could render cancers susceptible cisplatin-induced stress. Acetylation alters...
Significance Mutations in hTERT promoter are seen over 19% of human cancers, irrespective the cancer type. Understanding molecular players that regulate Mut- promoters may help design effective targeting strategies to inhibit telomerase reactivation specifically cells. Our work uses genome-wide functional screens identify 30 specific regulators promoters. These candidates identified from screening serve as an excellent resource understand how is reactivated and targets for making inhibitors...
Overexpression of epidermal growth factor receptor (EGFR), and downstream pathway activation appears to be a common oncogenic driver in the majority head neck squamous cell cancers (HNSCCs); yet targeting EGFR for treatment HNSCC has met with limited success. Apart from anti-EGFR antibody cetuximab, no small molecule EGFR/tyrosine kinase inhibitors (TKIs) have progressed routine clinical use. The aim this study was determine factors contributing lack response TKIs identify alternative...
Neuroblastoma is the commonest extracranial pediatric malignancy. With few recurrent single nucleotide variations (SNVs), mutation-based precision oncology approaches have limited utility, but its frequent and heterogenous copy number (CNVs) could represent genomic dependencies that may be exploited for personalized therapy. Patient-derived cell culture (PDC) models can facilitate rapid testing of multiple agents to determine such individualized drug-responses. Thus, study relationship...
Drug resistance and distant metastases are major contributors to mortality in colorectal cancer (CRC). Here we investigate mechanisms underlying acquired oxaliplatin, a first-line, standard-of-care CRC treatment. We generated oxaliplatin-resistant tumor cells with clinically relevant dosing regimen, which displayed enhanced metastatic potential. Transcriptomic phenotypic analyses revealed critical function for cholesterol biogenesis modulating TGFb signaling activity, turn regulates SERPINE1...
Abstract Transcription factors are important drivers of cancer but the development therapeutics against these has had limited success. We developed a stringent high-throughput chemical genetic screening platform to identify compounds that target oncogenic transcription factor SALL4 dependency in liver cancer. The comprises low- and high-expressing endogenous engineered isogenic cell lines. Unexpectedly, from 21,575 natural product extracts, top hits were four oxidative phosphorylation...