Zhongwu Lai
A5012973903- Lung Cancer Research Studies
- Neuroendocrine Tumor Research Advances
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Lung Cancer Treatments and Mutations
- CRISPR and Genetic Engineering
- BRCA gene mutations in cancer
- DNA Repair Mechanisms
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Genomics and Rare Diseases
- Science, Research, and Medicine
- Genetic factors in colorectal cancer
- Ovarian cancer diagnosis and treatment
- Lymphoma Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- Advanced Biosensing Techniques and Applications
- Cancer Treatment and Pharmacology
- Prostate Cancer Treatment and Research
AstraZeneca (United Kingdom)
2020-2025
AstraZeneca (United States)
2016-2025
Southern Medical University
2024
Nanfang Hospital
2024
AstraZeneca (Brazil)
2016-2023
Columbia University Irving Medical Center
2018
Centre Antoine Lacassagne
2018
Institut Curie
2018
Leiden University Medical Center
2018
Memorial Sloan Kettering Cancer Center
2018
A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion human genome was generated by whole-genome shotgun sequencing method. The 14.8-billion bp DNA over 9 months from 27,271,853 high-quality reads (5.11-fold coverage genome) both ends plasmid clones made five individuals. Two assembly strategies—a and a regional chromosome assembly—were used, each combining data Celera publicly funded effort. public were shredded into 550-bp segments to create 2.9-fold those regions...
Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes 1 deaths each year. Tenfold shotgun sequence coverage was obtained from PEST strain A. assembled into scaffolds span 278 base pairs. A total 91% genome organized in 303 scaffolds; largest scaffold 23.1 There substantial genetic variation within this strain, apparent existence two haplotypes approximately equal frequency ("dual haplotypes") fraction likely reflects outbred...
We report on the quality of a whole-genome assembly Drosophila melanogaster and nature computer algorithms that accomplished it. Three independent external data sources essentially agree with support assembly's sequence ordering contigs across euchromatic portion genome. In addition, there are isolated we believe represent nonrepetitive pockets within heterochromatin centromeres. Comparison previously sequenced 2.9- megabase region indicates sequencing accuracy segments is greater than 99....
Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile caller for both DNA- RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on fly more accurate allele frequency estimation. performance scales linearly depth, enabling ultra-deep used explore tumor...
Comparison of the genomes and proteomes two diptera Anopheles gambiae Drosophila melanogaster, which diverged about 250 million years ago, reveals considerable similarities. However, numerous differences are also observed; some these must reflect selection subsequent adaptation associated with different ecologies life strategies. Almost half genes in both interpreted as orthologs show an average sequence identity 56%, is slightly lower than that observed between pufferfish human (diverged...
Chromosome 2 of Plasmodium falciparum was sequenced; this sequence contains 947,103 base pairs and encodes 210 predicted genes. In comparison with the Saccharomyces cerevisiae genome, chromosome has a lower gene density, introns are more frequent, proteins markedly enriched in nonglobular domains. A family surface proteins, rifins, that may play role antigenic variation identified. The complete sequencing shown A+T-rich P. genome is technically feasible.
Abstract Genome-wide association studies have uncovered thousands of common variants associated with human disease, but the contribution rare to disease remains relatively unexplored. The UK Biobank contains detailed phenotypic data linked medical records for approximately 500,000 participants, offering an unprecedented opportunity evaluate effect variation on a broad collection traits 1,2 . Here we study relationships between protein-coding and 17,361 binary 1,419 quantitative phenotypes...
BackgroundBRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) enhanced sensitivity to DNA damaging agents or poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed clinical trials. Numerous mechanisms of PARPi resistance have described, whose relevance gBRCA-mutated cancer is unknown. This highlights the need identify functional biomarkers...
Abstract Resistance to targeted EGFR inhibitors is likely develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms these agents essential direct development future therapies. We describe the detection heterogeneous within populations cells (PC9 and/or NCI-H1975) with current and newly developed tyrosine kinase inhibitors, including AZD9291. report NRAS mutations, a novel E63K mutation, gain copy number WT KRAS cell resistant gefitinib, afatinib,...
Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option metastatic setting. Selumetinib (AZD6244, ARRY-142886) an oral, potent, and selective MEK1/2 inhibitor a short half-life, which demonstrated single-agent activity patients uveal randomized phase II trial. Methods The (AZD6244: (Hyd-Sulfate) Metastatic Melanoma (SUMIT) study was III, double-blind trial ( ClinicalTrial.gov identifier: NCT01974752) prior therapy were...
Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers sensitivity olaparib BRCA wild-type (BRCAwt) tumours. Tumour samples from an maintenance monotherapy trial (Study 19, D0810C00019; NCT00753545) were analysed. Analyses included classification...
Integrating human genomics and proteomics can help elucidate disease mechanisms, identify clinical biomarkers discover drug targets1-4. Because previous proteogenomic studies have focused on common variation via genome-wide association studies, the contribution of rare variants to plasma proteome remains largely unknown. Here we associations between protein-coding 2,923 protein abundances measured in 49,736 UK Biobank individuals. Our variant-level exome-wide study identified 5,433...
The high degree of similarity between the mouse and human genomes is demonstrated through analysis sequence chromosome 16 (Mmu 16), which was obtained as part a whole-genome shotgun assembly genome. genome about 10% smaller than genome, owing to lower repetitive DNA content. Comparison structure protein-coding potential Mmu with that homologous segments identifies regions conserved synteny chromosomes (Hsa) 3, 8, 12, 16, 21, 22. Gene content order are highly syntenic blocks Of 731 predicted...
DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, segmental duplications were integrated at level with medical genetic data, including 440 rearrangement breakpoints associated disease. This approach enabled discovery candidate genes for developmental diseases autism.
Abstract Purpose: Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity tumor tissue identify drug targets and patient-relevant models interrogate novel therapies. Following our development circulating patient–derived explants (CDX) as that faithfully mirror patient disease, here we exploit CDX examine new therapeutic options SCLC. Experimental Design: We...
Transforming growth factor-β activated kinase-1 (TAK1) is a member of the mitogen-activated protein kinase (MAP3K) family that regulates several signaling pathways including NF-κB signal transduction and p38 activation. TAK1 deregulation has been implicated in human diseases cancer inflammation. Here, we show that, addition to its activity, intrinsic ATPase (5Z)-7-Oxozeaenol irreversibly inhibits TAK1, sensitivity inhibition hematological cell lines NRAS mutation status pathway dependent....
Abstract Purpose: Maintenance therapy with olaparib has improved progression-free survival in women high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders olaparib. Experimental Design: A comparative molecular analysis Study 19 (NCT00753545), a randomized phase II trial assessing maintenance after response platinum-based chemotherapy HGSOC, conducted. LT defined...
Centrosome amplification is observed in many human cancers and has been proposed to be a driver of both genetic instability tumorigenesis. Cancer cells have evolved mechanisms bundle multiple centrosomes into two spindle poles avoid multipolar mitosis that can lead chromosomal segregation defects eventually cell death. KIFC1, kinesin-14 family protein, plays an essential role centrosomal bundling cancer cells, but its function not required for normal diploid division, suggesting KIFC1...
// Brian A. Dougherty 1 , Zhongwu Lai Darren R. Hodgson 2 Maria C.M. Orr 3 Matthew Hawryluk 4 James Sun Roman Yelensky Stuart K. Spencer 5 Jane D. Robertson Tony W. Ho 6 Anitra Fielding 7 Jonathan Ledermann 8 and J. Carl Barrett Innovative Medicines Early Development, Oncology, AstraZeneca, Waltham, MA, USA Cambridge, UK Personalized Healthcare Biomarkers, Foundation Medicine, Inc., Oncology Global Gaithersburg, MD, Macclesfield, UCL Cancer Institute, London, Correspondence to: Dougherty,...
Abstract Purpose: Not all patients with metastatic castration-resistant prostate cancer (mCRPC) have sufficient tumor tissue available for multigene molecular testing. Furthermore, samples may fail because of difficulties within the testing procedure. Optimization screening techniques reduce failure rates; however, a need remains additional methods to detect cancers alterations in homologous recombination repair genes. We evaluated utility plasma-derived circulating DNA (ctDNA) identifying...
Olaparib improved PFS and OS across subgroups of BRCA1/2mut #prostatecancer patients in the PROFOUND phase III trial.