A5084979512- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Colorectal Cancer Treatments and Studies
- Acute Myeloid Leukemia Research
- Lung Cancer Treatments and Mutations
- Molecular Biology Techniques and Applications
- Genetic factors in colorectal cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Genetic Associations and Epidemiology
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Genomic variations and chromosomal abnormalities
- Cutaneous Melanoma Detection and Management
- Bacteriophages and microbial interactions
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Carcinogens and Genotoxicity Assessment
- DNA Repair Mechanisms
- Advanced biosensing and bioanalysis techniques
- Epigenetics and DNA Methylation
Broad Institute
2024-2025
Novartis (United States)
2016-2023
Boston Biomedical Research Institute
2016-2022
Cardiff University
2019
Aarhus University
2019
Bayer (Germany)
2019
Peterborough City Hospital
2019
Skåne University Hospital
2019
University of Washington
2011-2016
Harvard University
2005-2009
Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation genotyping validation algorithm that enables robust setting.We developed implemented an optimized platform ("OncoMap") to interrogate approximately 400 33 known oncogenes suppressors, many which are response or resistance targeted therapies....
Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations development with shared neuropathologic features. These disorders are associated significant childhood morbidity mortality.To identify the underlying molecular cause FCD, diffuse megalencephaly.Patients or (mean age, 11.7 years; range, 2-32 years) were recruited from Pediatric Hospital A. Meyer, University Hong Kong, Seattle Children's Research Institute June 2012 to 2014....
<h3>Importance</h3> Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk atherosclerotic cardiovascular disease, and mouse experiments suggest that CHIP related to<i>Tet2</i>loss function in myeloid cells accelerates atherosclerosis via augmented interleukin (IL) 1β signaling. <h3>Objective</h3> To assess whether individuals have greater event reduction response to IL-1β neutralization the Canankinumab Anti-inflammatory Thrombosis Outcomes Trial (CANTOS)....
Abstract While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in V600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 trial of combined PD-1, sparatlizumab (PDR001), dabrafenib trametinib 37 patients CRC. The primary end point was overall rate, secondary points were...
Abstract Cancer genome alterations often lead to vulnerabilities that can be used selectively target cancer cells. Various inhibitors of such synthetic lethal targets have been approved by the FDA or are in clinical trials, highlighting potential this approach 1–3 . Here we analysed large-scale CRISPR knockout screening data from Dependency Map and identified a new target, PELO , for two independent molecular subtypes cancer: biallelic deletion chromosomal region 9p21.3 microsatellite...
Matched sequencing of both tumor and normal tissue is routinely used to classify variants uncertain significance (VUS) into somatic vs. germline. However, assays in molecular diagnostics focus on known alterations cancer genes often only sequence tumors. Therefore, an algorithm that reliably classifies would be helpful for retrospective exploratory analyses. Contamination samples with cells results differences expected allelic fractions germline variants, which can exploited accurately infer...
ALK rearrangements predict for sensitivity to tyrosine kinase inhibitors (TKIs). However, responses TKIs are generally short-lived. Serial molecular analysis is an informative strategy identifying genetic mediators of resistance. Although multiple studies support the clinical benefits repeat tissue sampling, utility longitudinal circulating tumor DNA has not been established in ALK-positive lung cancer.Using a 566-gene hybrid-capture next-generation sequencing (NGS) assay, we performed...
No approved targeted therapy for the treatment of patients with neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS)-mutant melanoma is currently available.In this phase Ib escalation/expansion study (ClinicalTrials.gov identifier: NCT02974725), safety, tolerability, and preliminary antitumor activity naporafenib (LXH254), a BRAF/CRAF protein kinases inhibitor, were explored in combination trametinib advanced/metastatic KRAS- or BRAF-mutant non-small-cell lung cancer (escalation arm)...
Abstract In patients with metastatic cancer, spatial heterogeneity of somatic alterations may lead to incomplete assessment a cancer’s mutational profile when analyzing single tumor biopsy. this study, we perform sequencing cell-free DNA (cfDNA) and distinct tissue samples from ten rapid autopsy cases pre-treated cancer. We show that levels in genetic biomarkers vary between but gene expression signatures representative the microenvironment are more consistent. Across nine plasma available,...
Abstract Purpose: The influence of the transcriptional and immunologic context mutations on therapeutic outcomes with targeted therapy in cancer has not been well defined. BRAF V600E–mutant (BM) colorectal comprises two main subtypes, BM1 BM2. We sought to determine impact BM subtype, as distinct biological features those response BRAF/MEK/EGFR inhibition patients cancer. Patients Methods: Paired fresh tumor biopsies were acquired at baseline day 15 treatment from all consenting enrolled a...
In the context of cancer, clonal hematopoiesis indeterminate potential (CHIP) is associated with development therapy-related myeloid neoplasms and shorter overall survival. Cell-free DNA (cfDNA) sequencing becoming widely adopted for genomic screening patients cancer but has not been used extensively to determine CHIP status because a requirement matched blood tumor sequencing. We present an accurate classification approach CH from cfDNA alone, applying our model 4324 oncology clinical...
Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential clinical diagnostics prognostics for guiding therapeutic development. Most currently available methods transcript compatible with Illumina RNA-seq involving highly accurate short-read sequences. Recent advances long-read isoform sequencing enable the at unprecedented resolution bulk single-cell samples. Here, we developed a new computational tool,...
Overrepresentation analysis (ORA) is used to identify the biological relationships in a list of genes by testing gene sets for enrichment query. However, inconsistent definition and highly overlapping nature set databases can make interpreting ORA results difficult. Here, we introduce GeneTEA, model that takes free-text descriptions incorporates several natural language processing methods learn sparse gene-by-term embedding, which be treated as de novo database. We benchmark performance...
Recurrent rearrangements of Chromosome 8p23.1 are associated with congenital heart defects and developmental delay. The complexity this region has led to inconsistencies in the current reference assembly, confounding studies genetic variation. Using comparative sequence-based approaches, we generated a high-quality 6.3-Mbp alternate assembly an inverted haplotype. Comparison nonhuman primates reveals 746-kbp duplicative transposition two separate inversion events that arose last million...
Asthma is a complex genetic disease caused by combination of and environmental risk factors. We sought to test classes variants largely missed genome-wide association studies (GWAS), including copy number (CNVs) low-frequency variants, performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched asthma-depleted families. The samples were obtained an extended 13-generation Hutterite pedigree with reduced heterogeneity due small founding gene pool as result communal...
The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity its complications, including type 2 diabetes. We genotyped a set 71 single nucleotide polymorphisms (SNPs) that capture the most common NPY, PPY, PYY, NPY1R, NPY2R, NPY5R 2,800 individuals recent European ancestry drawn from near extremes BMI distribution. Five SNPs located upstream NPY2R were nominally associated with men (P values =...
Due to the large size (150 kb) of ataxia-telangiectasia mutated (ATM) gene and existence over 400 mutations, identifying mutations in patients with (A-T) is labor intensive. We compared SNP STR haplotypes A-T from varying ethnicities who were carrying common ATM mutations. used SSCP determine haplotypes. To our surprise, all most multiethnic cohort associated specific haplotypes, whereas varied, suggesting that predated but not conclude these frequently observed are hot spots, have occurred...