A5069185084- Cancer Genomics and Diagnostics
- Bladder and Urothelial Cancer Treatments
- Single-cell and spatial transcriptomics
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Computational Drug Discovery Methods
- Molecular Biology Techniques and Applications
- Urinary and Genital Oncology Studies
- Ovarian cancer diagnosis and treatment
- Gene expression and cancer classification
- Genetic factors in colorectal cancer
- Metastasis and carcinoma case studies
- Bioinformatics and Genomic Networks
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Genetic and phenotypic traits in livestock
- Genomics and Phylogenetic Studies
- Lung Cancer Treatments and Mutations
- Esophageal Cancer Research and Treatment
- Innovative Microfluidic and Catalytic Techniques Innovation
- CRISPR and Genetic Engineering
- Lung Cancer Research Studies
- Genetics, Bioinformatics, and Biomedical Research
- Genetic diversity and population structure
Novartis (United States)
2014-2024
Dana-Farber Cancer Institute
2012-2023
Harvard University
2012-2023
Lagos State University Teaching Hospital
2016-2017
University of Ibadan
2016-2017
University of Chicago
2016-2017
Center for Global Health
2017
Lagos State University
2016-2017
Center for Cancer Research
2013-2016
Massachusetts General Hospital
2013-2016
Plant microRNAs (miRNAs) affect only a small number of targets with high sequence complementarity, while animal miRNAs usually have hundreds limited complementarity. We used artificial (amiRNAs) to determine whether the narrow action spectrum natural plant reflects intrinsic properties miRNA machinery or it is also due past selection against broader specificity. amiRNAs were designed target individual genes groups endogenous genes. Like miRNAs, they had varying numbers mismatches. Previously...
Abstract The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) has led to the clinical development JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms myelofibrosis improves overall survival; however, mechanism by which inhibitors achieve efficacy not been delineated. Patients MPN present increased levels circulating proinflammatory cytokines, are mitigated inhibitor therapy. We sought elucidate...
Abstract Despite the increasing interest in targeting stromal elements of tumor microenvironment, we still face tremendous challenges developing adequate therapeutics to modify landscape. A major obstacle this is our poor understanding phenotypic and functional heterogeneity cells tumors. Herein, perform an unbiased interrogation mesenchymal cells, delineating co-existence distinct subsets cancer-associated fibroblasts (CAFs) microenvironment murine carcinomas, each endowed with unique...
Abstract Purpose: We aimed to validate and improve prognostic signatures for high-risk urothelial carcinoma of the bladder. Experimental Design: evaluated microarray data from 93 patients with bladder cancer managed by radical cystectomy determine gene expression patterns associated clinical variables. compared our results published sets comprising 578 additional 49 multiple types. Hierarchical clustering was utilized identify subtypes differences in survival. then investigated whether...
This article introduces a manually curated data collection for gene expression meta-analysis of patients with ovarian cancer and software reproducible preparation similar databases. resource provides uniformly prepared microarray 2970 from 23 studies documented clinical metadata. It allows users to efficiently identify patient subgroups interest analysis perform immediately without the challenges posed by harmonizing heterogeneous technologies, study designs, processing methods formats. We...
Two recent phase III trials, BOLERO-1 and BOLERO-3 (Breast Cancer Trials of Oral Everolimus), evaluated the addition everolimus to trastuzumab chemotherapy in human epidermal growth factor receptor 2-overexpressing advanced breast cancer. The current analysis aimed identify biomarkers predict clinical efficacy treatment.Archival tumor samples from patients were analyzed using next-generation sequencing, immunohistochemistry, Sanger sequencing.Biomarker data available for 549 patients. PIK3CA...
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...
Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology, their contributions to the malignant phenotype remain poorly understood. Here we studied genome-wide DNA methylation normal B-cell populations and subtypes of non-Hodgkin lymphoma: follicular lymphoma diffuse large lymphomas. These lymphomas display striking progressive intra-tumor heterogeneity also inter-patient cytosine patterns. Epigenetic is initiated germinal center B-cells, increases markedly...
Abstract Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of cancers using 194 patients from Nigeria 1037 The Cancer Genome Atlas (TCGA). Relative Black White cohorts TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, greater structural...
Abstract Motivation: Numerous competing algorithms for prediction in high-dimensional settings have been developed the statistical and machine-learning literature. Learning models they generate are typically evaluated on basis of cross-validation error estimates a few exemplary datasets. However, most applications, ultimate goal modeling is to provide accurate predictions independent samples obtained different settings. Cross-validation within datasets may not adequately reflect performance...
Abstract Multiomics experiments are increasingly commonplace in biomedical research and add layers of complexity to experimental design, data integration, analysis. R Bioconductor provide a generic framework for statistical analysis visualization, as well specialized classes variety high-throughput types, but methods lacking integrative multiomics experiments. The MultiAssayExperiment software package, implemented leveraging design principles, provides the coordinated representation of,...
Abstract Multiple studies have identified transcriptome subtypes of high-grade serous ovarian carcinoma (HGSOC), but their interpretation and translation are complicated by tumor evolution polyclonality accompanied extensive accumulation somatic aberrations, varying cell type admixtures, different tissues origin. In this study, we examined the chronology HGSOC subtype in context these factors using a novel integrative analysis absolute copy-number gene expression The Cancer Genome Atlas...
Abstract Background Deregulation of FGF19-FGFR4 signaling is found in several cancers, including hepatocellular carcinoma (HCC), nominating it for therapeutic targeting. FGF401 a potent, selective FGFR4 inhibitor with antitumor activity preclinical models. This study was designed to determine the recommended phase 2 dose (RP2D), characterize PK/PD, and evaluate safety efficacy alone combined anti-PD-1 antibody, spartalizumab. Methods Patients HCC or other FGFR4/KLB expressing tumors were...
Abstract Summary: We present a software package for pedigree reconstruction in natural populations using co-dominant genomic markers such as microsatellites and single nucleotide polymorphisms (SNPs). If available, the algorithm makes use of prior information known relationships (sub-pedigrees) or age sex individuals. Statistical confidence is estimated by Markov Chain Monte Carlo (MCMC) sampling. The accuracy demonstrated simulated data well an empirical dataset with pedigree. parentage...
While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown muscle-invasive disease. mRNA expression, mutational status, copy number variation were retrospectively analyzed 231 patients with formalin-fixed paraffin-embedded primary UCs, 33 metastases, 14 paired metastatic tumors using following methods: immunohistochemistry, NanoString...
Metastatic urothelial carcinoma of the bladder is associated with multiple somatic copy-number alterations (SCNAs). We evaluated SCNAs to identify predictors poor survival in patients metastatic treated platinum-based chemotherapy.We obtained overall (OS) and array DNA data from two cohorts. Associations between recurrent OS were determined by a Cox proportional hazard model adjusting for performance status visceral disease. mRNA expression was potential candidate genes NanoString nCounter...
Abstract We evaluated primary tumors from two cohorts, Spain ( N = 111) and Greece 102), for patients who were treated with platinum‐based chemotherapy. Patients tested HER2 status IHC score of 3+ or FISH ratio ≥2.2) by immunohistochemistry ), fluorescence in situ hybridization DNA copy number, mRNA expression, mutation metastatic urothelial carcinoma UC its impact on survival. ERBB2 was determined hotspot sequencing. expression assessed using NanoString counting. Association overall...