A5023411724- Epigenetics and DNA Methylation
- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Genetic Associations and Epidemiology
- Renal cell carcinoma treatment
- Neonatal Respiratory Health Research
- Gene expression and cancer classification
- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Genetic Mapping and Diversity in Plants and Animals
- Estrogen and related hormone effects
- Renal and related cancers
- Nutrition, Genetics, and Disease
- Colorectal Cancer Screening and Detection
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Testicular diseases and treatments
- Cancer-related molecular mechanisms research
- Sexual Differentiation and Disorders
- Genetic and phenotypic traits in livestock
- Prostate Cancer Treatment and Research
- Health, Environment, Cognitive Aging
Keck Hospital of USC
2010-2025
University of Southern California
2015-2024
General Department of Preventive Medicine
2004-2016
USC Norris Comprehensive Cancer Center
1999-2016
Southern California University for Professional Studies
2002-2013
Tochigi Cancer Center
2010
University of North Carolina at Chapel Hill
1998-2010
Arizona Oncology
2010
Denver VA Medical Center
2010
University of Hawaiʻi at Mānoa
2009-2010
We propose a novel approach to background correction for Infinium HumanMethylation data account technical variation in fluorescence signal. Our capitalizes on new use the I design bead types measure non-specific colour channel opposite of their (Cy3/Cy5). This provides tens thousands features measuring instead much smaller number negative control probes platforms (n = 32 HumanMethylation27 and n 614 HumanMethylation450, respectively). compare performance our methods with existing approaches,...
Lung cancer is the leading cause of death worldwide, and adenocarcinoma its most common histological subtype. Clinical molecular evidence indicates that lung a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using Illumina Infinium HumanMethylation27 platform on 59 matched adenocarcinoma/non-tumor pairs, with verification an independent set tissues. We identified 766 genes showing altered between tumors non-tumor...
The role of DNA cytosine methylation, an epigenetic regulator chromatin structure and function, during normal pathological brain development aging remains unclear. Here, we examined by MethyLight PCR the methylation status at 50 loci, encompassing primarily 5' CpG islands genes related to CNS growth development, in temporal neocortex 125 subjects ranging age from 17 weeks gestation 104 years old. Two psychiatric disease cohorts--defined chronic neurodegeneration (Alzheimer's) or lack thereof...
It was recently shown that a large portion of the human transcriptome can originate from within repetitive elements, leading to ectopic expression protein-coding genes. However mechanism transcriptional activation elements has not been definitively elucidated. For first time, we directly demonstrate hypomethylation retrotransposons cause altered gene in humans. We also reveal active LINE-1s switch tetranucleosome dinucleosome structure, acquiring H2A.Z- and nucleosome-free regions upstream...
Bisulfite treatment of DNA followed by high-throughput sequencing (Bisulfite-seq) is an important method for studying methylation and epigenetic gene regulation, yet current software tools do not adequately address single nucleotide polymorphisms (SNPs). Identifying SNPs accurate quantification levels identification allele-specific events such as imprinting. We have developed a model-based bisulfite SNP caller, Bis-SNP, that results in substantially better calls than existing methods,...
Abstract We have generated DNA methylation profiles of 148 human breast tumors and found significant differences in hormone receptor (HR) status between clusters profiles. Of 35 markers analyzed, the ESR1 gene, encoding estrogen α, proved to be best predictor progesterone status, whereas PGR receptor, was status. outperformed HR as a clinical response patients treated with antiestrogen tamoxifen, promoter CYP1B1 tamoxifen- estradiol-metabolizing cytochrome P450, predicted differentially...
Male-factor infertility is a common condition, and etiology unknown for high proportion of cases. Abnormal epigenetic programming the germline proposed as possible mechanism compromising spermatogenesis some men currently diagnosed with idiopathic infertility. During germ cell maturation gametogenesis, cells line undergo extensive reprogramming. This process involves widespread erasure somatic-like patterns DNA methylation followed by establishment sex-specific de novo methylation....
DNA methylation is known to be associated with cell differentiation, aging, disease and cancer. There exists an expanding base of knowledge regarding tissue-specific methylation, but we have little information about person-specific methylation. Here, analyze the patterns multiple tissues from individuals using a high-throughput quantitative assay genome-wide namely Illumina GoldenGate BeadArray. were largely conserved across 11 different (r = 0.852) six 0.829), found that was highly...
There is increasing evidence for a fundamental role epigenetic silencing of apoptotic pathways in cancer. Changes DNA methylation can be detected with high degree sensitivity, so we used the MethyLight assay to determine how patterns apoptosis-associated genes change during bladder carcinogenesis and whether could urine sediments.We analyzed status 5' regions 12 (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, EDNRB) 18 cancer cell lines, 127 samples, 37 samples...
Abstract Microsatellite instability (MSI) occurs in 10% to 20% of colorectal cancers (CRC) and has been attributed both MLH1 promoter hypermethylation germline mutation the mismatch repair (MMR) genes. We present results from a large population- clinic-based study methylation, immunohistochemistry, MMR mutations that enabled us (a) estimate prevalence methylation among MSI-H cases help understand if all CRC is explained by these mechanisms (b) associations between sex, age, tumor location...
Abstract Urothelial cancer (UC) develops along two different genetic pathways, resulting in noninvasive or invasive tumors. However, it is unknown whether there are also epigenetic pathways UC. UC characterized by a high rate of recurrence, and the presence field defect has been postulated. In this study, we compared DNA methylation patterns between normal-appearing urothelium from bladders with cancer-free bladders. We used Illumina GoldenGate assay at 1,370 loci 49 urothelial tumors, 38...
Cancers are clonal expansions, but how a single, transformed human cell grows into billion-cell tumor is uncertain because serial observations impractical. Potentially, this history surreptitiously recorded within genomes that become increasingly numerous, polymorphic, and physically separated after transformation. To correlate physical with epigenetic pairwise distances, small 2,000- to 10,000-cell gland fragments were sampled from left right sides of 12 primary colorectal cancers,...
Histone H3 lysine-9 methyltransferase G9a/EHMT2/KMT1C is a key corepressor of gene expression. However, activation limited number genes by G9a (independent its catalytic activity) has also been observed, although the precise molecular mechanisms are unknown. By using RNAi in combination with expression microarray analysis, we found that functions as positive and negative transcriptional coregulator for discrete subsets regulated hormone-activated Glucocorticoid Receptor (GR). was recruited...
Background Smoking while pregnant is associated with a myriad of negative health outcomes in the child. Some detrimental effects may be due to epigenetic modifications, although few studies have investigated this hypothesis detail. Objectives To characterize site-specific modifications conferred by prenatal smoking exposure within asthmatic children. Methods Using Illumina HumanMethylation27 microarrays, we estimated degree methylation at 27,578 distinct DNA sequences located primarily gene...
A fundamental task in neuroscience is to characterize the brain's developmental course. While replicable group-level models of structural brain development from childhood adulthood have recently been identified, we yet quantify and understand individual differences development. The present study examined inter-individual variability sex changes structure, as assessed by anatomical MRI, across ages 8.0-26.0 years 269 participants (149 females) with three time points data (807 scans), drawn...
Background:Although exposure to ambient air pollutants increases cardiovascular disease risk in adults little is known about the effects of prenatal exposure. Genetic variation and epigenetic alterations are two mechanisms that may influence early-life exposures on phenotypes.Objectives:We investigated whether genetic modify associations between pollution markers childhood.Methods:We used linear regression analysis investigate (PM2.5, PM10, NO2, O3), long interspersed nuclear elements...
We have investigated the regulation of genes and associated molecular pathways, genome-wide, in oral cells electronic cigarette (e-cigs) users smokers as compared to non-smokers. Interrogation transcriptome by RNA-sequencing (RNA-seq) analysis showed significant number aberrantly expressed transcripts both e-cig (vapers) relative non-smokers; however, had ~50% more differentially than vapers (1726 versus 1152). Whereas deregulated were predominately from protein-coding (79% 53% vapers),...