A5052817116- RNA modifications and cancer
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Head and Neck Cancer Studies
- Genomics and Chromatin Dynamics
- Lung Cancer Treatments and Mutations
- Histone Deacetylase Inhibitors Research
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- RNA and protein synthesis mechanisms
- Click Chemistry and Applications
- Bioinformatics and Genomic Networks
- Radiomics and Machine Learning in Medical Imaging
- Plant Disease Resistance and Genetics
- Pancreatic and Hepatic Oncology Research
- Hedgehog Signaling Pathway Studies
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Congenital heart defects research
University of Maryland Medical Center
2021-2025
Johns Hopkins University
2016-2025
University of Maryland, Baltimore
2021-2025
Sidney Kimmel Comprehensive Cancer Center
2020-2025
University of Baltimore
2010-2024
University of Maryland Medical System
2023-2024
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
2022-2024
Kosin University Gospel Hospital
2024
Thomas Jefferson University
2024
Human Genome Sciences (United States)
2024
Abstract NOTCH1 mutations have been reported to occur in 10% 15% of head and neck squamous cell carcinomas (HNSCC). To determine the significance these mutations, we embarked upon a comprehensive study NOTCH signaling cohort 44 HNSCC tumors 25 normal mucosal samples through set expression, copy number, methylation, mutation analyses. Copy number increases were identified pathway genes, including ligand JAG1. Gene analysis defined differential expression relative tissues. Analysis individual...
In eukaryotic genomes, nucleosomes function to compact DNA and regulate access it both by simple physical occlusion providing the substrate for numerous covalent epigenetic tags. While competition with other DNA-binding factors action of chromatin remodeling enzymes significantly affect nucleosome formation in vivo, positions vitro are determined steric exclusion sequence alone. We have developed a biophysical model, DNABEND, dependence bending energies, validated against collection free...
Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways even individual malignant cells. Epigenetic changes are critical mediators of these functional that drive and maintain the phenotype. Changes DNA methylation, histone acetylation noncoding RNAs, posttranslational modifications all epigenetic drivers cancer, independent sequence. These alterations were once thought to be crucial only for phenotype maintenance. Now, also recognized as disrupting essential...
Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine methylation, chromatin marks, and alterations to define relationship between modulation spatial structure. Using human papillomavirus-related oropharyngeal carcinoma a model, show aberrant enrichment repressive H3K9me3 at...
Abstract The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized episomal E2, E4, E5 (E2/E4/E5) expression. Half positive cervical pharyngeal cancers comprised a subtype with increase in E2/E4/E5, as well association lack genome. Models E2/E4/E5 show p53 dependent enhanced proliferation vitro, increased susceptibility to induction cancer vivo. Whole...
Therapeutic combinations to alter immunosuppressive, solid tumor microenvironments (TME), such as in breast cancer, are essential improve responses immune checkpoint inhibitors (ICI). Entinostat, an oral histone deacetylase inhibitor, has been shown ICIs various models with immunosuppressive TMEs. The precise and comprehensive alterations the TME induced by entinostat remain unknown. Here, we employed single-cell RNA sequencing on HER2-overexpressing tumors from mice treated fully...
Development of head and neck squamous cell carcinoma (HNSCC) is characterized by accumulation mutations in several oncogenes tumor suppressor genes. We have formerly described the mutation pattern HNSCC NOTCH signaling pathway alterations. Given complexity HNSCC, here we extend previous study to understand overall context discover additional genetic performed high depth targeted exon sequencing 51 highly actionable cancer-related genes with a frequency across many cancer types, including...
Thousands of human and Drosophila genes are regulated at the level transcript elongation nucleosomes likely targets for this regulation. However, molecular mechanisms formation nucleosomal barrier to transcribing RNA polymerase II (Pol II) nucleosome survival during/after transcription remain unknown. Here we show that both DNA-histone interactions Pol backtracking contribute during occurs through allosterically stabilized histone-histone interactions. Structural analysis indicates after...
Chromatin alterations mediate mutations and gene expression changes in cancer. immunoprecipitation followed by sequencing (ChIP-Seq) has been utilized to study genome-wide chromatin structure human cancer cell lines, yet numerous technical challenges limit comparable analyses primary tumors. Here we have developed a new whole-genome analytic pipeline optimize ChIP-Seq protocols on patient-derived xenografts from papillomavirus-related (HPV+) head neck squamous carcinoma (HNSCC) samples. We...
Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head neck squamous cell carcinoma (HNSCC) subgroups by inferential analysis target gene expression, correcting for effects DNA methylation copy number. this discovery pipeline, determined that human papillomavirus-related (HPV+) HPV- HNSCC differed significantly based on activity levels key TFs including AP1, STATs, NF-κB p53. Immunohistochemical confirmed is co-activated STAT3 pathways functional...
Non-negative Matrix Factorization (NMF) algorithms associate gene expression with biological processes (e.g. time-course dynamics or disease subtypes). Compared univariate associations, the relative weights of NMF solutions can obscure biomarkers. Therefore, we developed a novel patternMarkers statistic to extract genes for validation and enhanced visualization results. Finding unbiased markers requires whole-genome data. also Genome-Wide CoGAPS Analysis in Parallel Sets (GWCoGAPS), first...
The Cancer Genome Atlas (TCGA) sequencing analysis of head and neck squamous cell carcinoma (HNSCC) recently reported on gene fusions, however, few human papillomavirus (HPV) positive samples were included, the functional relevance identified fusions was not explored. We therefore performed an independent in HPV-positive oropharyngeal SCC (OPSCC). RNA 47 OPSCC primary tumors 25 normal mucosal from cancer unaffected controls Illumina TruSeq platform. MapSplice2 used for alignment...
Identifying potential resistance mechanisms while tumour cells still respond to therapy is critical delay acquired resistance.
Abstract This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, Sparse-L1 algorithm used select functional features, which were then build Cox...
Abstract Pancreatic ductal adenocarcinoma (PDA) is characterized by low cytotoxic lymphocytes, abundant immune-suppressive cells, and resistance to immune checkpoint inhibitors (ICI). Preclinical PDA models showed the HDAC inhibitor entinostat reduced myeloid cell immunosuppression, sensitizing tumors ICI therapy. This phase II study combined with nivolumab (PD1 inhibitor) in patients advanced (NCT03250273). Patients received 5 mg orally once weekly for 14-day lead-in, followed nivolumab....
Abstract Purpose: Aim of this study was to determine whether BORIS (Brother the Regulator Imprinted Sites) is a regulator MAGEA2, MAGEA3, and MAGEA4 genes in lung cancer. Experimental Design: Changes expression MAGEA upon induction/knockdown were studied. Recruitment changes histone modifications at their promoters induction analyzed. Luciferase assays used activation by BORIS. methylation these evaluated. Results: Alteration directly correlated with genes. enriched H1299 cells, which show...
Abstract Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm HPV-positive cancer (HPV-OPC). HPV16 E6 antibody precedes diagnosis. If indeed primary diagnosis, it similarly expected to precede disease recurrence and may have a potential role as biomarker HPV-OPC. To determine whether HPV titers early markers or prognosis, retrospective pilot study was designed E6, E7, E1, E2 decrease...
The incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has increased more than 200% in the past 20 years. Recent genetic sequencing efforts have elucidated relevant genes head and neck cancer, but tumors consistently shown few DNA mutations. In this study, we sought to analyze alternative splicing events (ASE) that could alter gene function independent To identify ASE unique tumors, RNA was performed on 46 HPV-positive OPSCC 25 normal tissue samples. A novel algorithm...
Human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) exhibits a different composition of epigenetic alterations. In this study, we identified differentially methylated regions (DMRs) with potential utility in screening for HPV‐positive OPSCC. Genome wide DNA methylation was measured using methyl‐CpG binding domain protein‐enriched genome sequencing (MBD‐seq) 50 OPSCC tissues and 25 normal tissues. Fifty‐one DMRs were defined maximal specificity to cancer samples....