Project description:Here, we present the first study showing race and side-specific differences in the trajectories of epigenetic aging in normal colonic mucosa. The cohort conisted of matched biopsies of left/right colon from healthy individuals (n=129). The majority of individuals were African American (n=89). Methylation arrays (Illumina EPIC) were performed on DNA extracted from fresh frozen biopsies taken at the time of colonoscopy. Our results provide novel insight of epigenetic aging underlying racial disparities in CRC. Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC burden.
Project description:Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.
Project description:Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.
Project description:Left and Right phrenic nerves, which innervate the left and right diaphragm muscles, exhibit different innervation patterns. This left/right (L/R) asymmetry is established at the onset of innervation by a developmental program that requires Nodal. Phenotype analysis suggests that the cervical motoneurons, which innervate the diaphragm, have a L/R imprint that contributes to set the L/R asymmetries of innervation. We used microarray to analyze the expression profile of left and right cervical motoneurons before diaphragm innervation
Project description:The right and left atria have different susceptibilities towards developing arrhythmias, with left atrial arrhythmias more commonly observed. To study potential underlying causes of this difference between the two upper chambers of the heart, four human left-right atrial pairs were subjected to whole-genome expression analyses via next generation sequencing of small RNAs, including microRNAs (miRNAs), and polyA enriched mRNAs. Using a paired sample design, significant differences in gene expression were found between the left and right atria in both the poly-A and small RNA fractions. Hsa-miR-143 was the most highly expressed miRNA in the atria as quantified by RNA-seq. Gene expression differences established during development are retained into adulthood including that of PITX2 and BMP10. In addition ten novel non-coding RNAs were found to be differentially expressed between the left and right atrias .
Project description:Analysis of miRNA expression in colon biopsies from Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) control subjects.
Project description:Colon gene expression in human IBD. The three major clinical subsets of Inflammatory Bowel Disease (IBD) include colon-only Crohn's Disease (CD), ileo-colonic CD, and Ulcerative Colitis (UC). These experiments tested differential colon gene expression in these three types of IBD, relative to healthy control samples, and the local degree of mucosal inflammation as measured by the CD Histological Index of Severity (CDHIS). Colon biopsy samples were obtained from IBD patients at diagnosis and during therapy, and healthy controls. The global pattern of gene expression was determined using GeneSpring software, with a focus upon candidate genes identified in a recent genome wide association study in pediatric onset IBD. Data suggested that two of these candidate genes are up regulated in pediatric IBD, partially influenced by local mucosal inflammation. These experiments tested differential colon gene expression in healthy, CD, and UC samples for candidate genes identified in a recent pediatric onset IBD genome wide association study. Keywords: Single time point in CD and UC and healthy controls.
Project description:Left and right heart ventricles of adult male mice were profiled to determine the differences in gene expression, control, coordination and signaling fabrics Two-sides (L= left, R = right) gene expression profiling experiment in adult mouse male (M) ventricles (V). 4 biological replicates: MVL1-4, MVR1-4.