Daniel Lai
A5046137014- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Gene expression and cancer classification
- RNA and protein synthesis mechanisms
- Ovarian cancer diagnosis and treatment
- Evolution and Genetic Dynamics
- Chronic Lymphocytic Leukemia Research
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Breast Cancer Treatment Studies
- Health, Environment, Cognitive Aging
- Cancer-related gene regulation
University of Birmingham
2025
University of British Columbia
2014-2024
BC Cancer Agency
2016-2024
Hong Kong Polytechnic University
2024
Molecular Oncology (United States)
2017-2023
Terry Fox Research Institute
2022
Provincial Health Services Authority
2021
Cancer Research UK Cambridge Center
2021
Cambridge University Hospitals NHS Foundation Trust
2021
Spinal Cord Injury BC
2019-2020
Abstract G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting for cancer treatment is a very promising prospect. Here, we show that CX-5461 stabilizer, with specific toxicity against BRCA deficiencies cells polyclonal patient-derived xenograft models, including tumours resistant PARP inhibition. Exposure CX-5461, its related drug CX-3543, blocks replication forks induces ssDNA gaps or breaks. The NHEJ pathways...
Loss of heterozygosity (LOH) and copy number alteration (CNA) feature prominently in the somatic genomic landscape tumors. As such, karyotypic aberrations cancer genomes have been studied extensively to discover novel oncogenes tumor-suppressor genes. Advances sequencing technology enabled cost-effective detection tumor genome transcriptome mutation events at single-base-pair resolution; however, computational methods for predicting segmental regions LOH this context are not yet fully...
Abstract We performed a genomic, transcriptomic, and immunophenotypic study of 347 patients with diffuse large B-cell lymphoma (DLBCL) to uncover the molecular basis underlying acquired deficiency MHC expression. Low MHC-II expression defines tumors originating from centroblast-rich dark zone germinal center (GC) that was associated inferior prognosis. MHC-II–deficient were characterized by somatically gene mutations reducing lower amount tumor-infiltrating lymphocytes. In particular, we...
Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying complex biological systems, such as tumor heterogeneity and tissue microenvironments. However, the sources of technical variation in primary solid tissues patient-derived mouse xenografts scRNA-seq are not well understood.
Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, open source computational methods. Using we generated resource 51,926 matched cell images diverse types including lines, xenografts, diagnostic samples with limited...
Abstract A holistic understanding of tissue and organ structure function requires the detection molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous up to 40 antigens transcripts using metal-tagged antibodies but has so far been restricted two-dimensional imaging. Here we report development 3D IMC for multiplexed analysis at single-cell resolution demonstrate utility technology by human breast cancer samples. The resulting...
How cell-to-cell copy number alterations that underpin genomic instability
Abstract CX-5461 is a G-quadruplex stabilizer that exhibits synthetic lethality in homologous recombination-deficient models. In this multicentre phase I trial patients with solid tumors, 40 are treated across 10 dose levels (50–650 mg/m 2 ) to determine the recommended II (primary outcome), and evaluate safety, tolerability, pharmacokinetics (secondary outcomes). Defective recombination explored as predictive biomarker of response. generally well tolerated, 475 days 1, 8 15 every 4 weeks,...
Abstract Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis strongly associated with molecular subgroup, although the driver mutations that distinguish two main subgroups remain poorly defined. Through integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes non-coding loci are commonly mutated in DLBCL. Our has identified novel cis -regulatory sites, implicates recurrent 3′ UTR NFKBIZ as a mechanism...
Visually examining RNA structures can greatly aid in understanding their potential functional roles and evaluating the performance of structure prediction algorithms. As many already be studied given secondary RNA, various methods have been devised for visualizing structures. Most these depict a as planar graph consisting base-paired stems interconnected by roundish loops. In this article, we present an alternative method depicting arc diagrams. This is well suited that are difficult or...
Measuring gene expression of tumor clones at single-cell resolution links functional consequences to somatic alterations. Without scalable methods simultaneously assay DNA and RNA from the same single cell, parallel measurements independent cell populations must be mapped for genome-transcriptome association. We present clonealign, which assigns states cancer using sequencing independently sampled a heterogeneous population. apply clonealign triple-negative breast patient-derived xenografts...
Long QT syndrome (LQTS) is an autosomal dominant condition predisposing to sudden death from malignant arrhythmia. Genetic testing identifies many missense single nucleotide variants of uncertain pathogenicity. Establishing genetic pathogenicity essential prerequisite family cascade screening. Many laboratories use in silico prediction tools, either alone or combination, metaservers, order predict pathogenicity; however, their accuracy the context LQTS unknown. We evaluated five programs and...
Abstract Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis triple negative breast cancer (TNBC) not yet well understood. Here we determined the prevalence of actionable mutations detectable ctDNA using a clinically validated gene panel assay patients with TNBC, without recurrence at time study entry. Sequencing plasma validation variants from 130 TNBC collected within 7...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDistribution and metabolism of glycoproteins glycosaminoglycans in subcellular fractions brainR. K. Margolis, R. U. C. Preti, D. LaiCite this: Biochemistry 1975, 14, 22, 4797–4804Publication Date (Print):November 4, 1975Publication History Published online1 May 2002Published inissue 4 November 1975https://pubs.acs.org/doi/10.1021/bi00693a004https://doi.org/10.1021/bi00693a004research-articleACS PublicationsRequest reuse permissionsArticle...
Abstract Endometrial carcinoma, the most common gynaecological cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification unreliable there a need for prognostic tools. We used single cell sequencing to study organoid model systems derived normal endometrium discover novel markers specific or A marker cells (MPST) several (FAM92B, WDR16, DYDC2) were validated by immunohistochemistry on organoids tissue sections. performed ovarian...
The heterogeneity of breast cancer plays a major role in drug response and resistance has been extensively characterized at the genomic level. Here, single-cell mass cytometry (BCMC) panel is optimized to identify cell phenotypes their oncogenic signalling states biobank patient-derived tumour xenograft (PDTX) models representing diversity human cancer. BCMC identifies 13 cellular (11 2 murine), associated with both subtypes specific features. Pre-treatment phenotypic composition determinant...