A5004031719- Genetic factors in colorectal cancer
- Gastric Cancer Management and Outcomes
- Colorectal Cancer Treatments and Studies
- Helicobacter pylori-related gastroenterology studies
- Colorectal Cancer Screening and Detection
- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Arsenic contamination and mitigation
- Genomics, phytochemicals, and oxidative stress
- Carcinogens and Genotoxicity Assessment
- Hepatitis C virus research
- Pharmacogenetics and Drug Metabolism
- Retinoids in leukemia and cellular processes
- Cholangiocarcinoma and Gallbladder Cancer Studies
- RNA modifications and cancer
- Cancer Diagnosis and Treatment
- Eosinophilic Disorders and Syndromes
- Glutathione Transferases and Polymorphisms
- Heavy Metal Exposure and Toxicity
- Drug Transport and Resistance Mechanisms
- Water Treatment and Disinfection
- Birth, Development, and Health
- Eosinophilic Esophagitis
- Inflammatory mediators and NSAID effects
- Ion Transport and Channel Regulation
National Institute of Environmental Health Sciences
2022-2025
National Institutes of Health
2023-2025
Triangle
2022-2023
University of Utah
2011-2021
Huntsman Cancer Institute
2011-2019
University of Utah Health Care
2019
Huazhong University of Science and Technology
2013
Tongji Hospital
2013
Research Triangle Park Foundation
2006-2011
Environmental Protection Agency
2005-2011
Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease. Liver inflammation underlies infection-induced fibrosis, cirrhosis and cancer but the processes that promote hepatic by HCV are not defined. We provide systems biology analysis with multiple lines evidence to indicate interleukin-1β (IL-1β) production intrahepatic macrophages confers through HCV-induced inflammasome signaling. patients exhibited elevated levels serum IL-1β compared healthy controls....
Abstract Bile acid (BA) metabolism is tightly controlled by nuclear receptor signaling to coordinate regulation of BA synthetic enzymes and transporters. Here we reveal a molecular cascade consisting the antiapoptotic protein BCL2, Shp long non-coding RNA (lncRNA) H19 maintain homeostasis. Bcl2 was overexpressed in liver C57BL/6J mice using adenovirus mediated gene delivery for two weeks. Hepatic overexpression caused drastic accumulation serum bilirubin levels dysregulated reactivation...
In a previously developed mouse model, arsenic exposure in utero induces tumors at multiple sites the offspring as adults, often duplicating human targets. However, environmental inorganic occurs during entire life span, not just part of gestation. Thus, "whole-life" carcinogenesis mice was studied. CD1 were exposed to 0, 6, 12, or 24 ppm drinking water 2 weeks prior breeding, pregnancy, lactation, and after weaning through adulthood. Tumors assessed until years age. Arsenic induced...
Conazoles comprise a class of fungicides used in agriculture and as pharmaceutical products. The fungicidal properties conazoles are due to their inhibition ergosterol biosynthesis. Certain tumorigenic rodents; both propiconazole triadimefon hepatotoxic hepatotumorigenic mice, while myclobutanil is not mouse liver tumorigen. As component large-scale study aimed at determining the mode(s) action for conazoles, we report results from comparative evaluations body weights, histopathology, cell...
Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have common mode antifungal action through inhibition ergosterol biosynthesis. Some members this been shown to be hepatotoxic will induce mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. The particular toxic tumorigenic for these compounds is not known, however it has proposed that triadimefon-induced arise the specific mechanism increased TSH. present study was...
The molecular mechanisms behind human liver disease progression to cirrhosis remain elusive. Nuclear receptor small heterodimer partner (SHP/Nr0b2) is a hepatic tumor suppressor and critical regulator of function. SHP expression diminished in cirrhotic livers, suggesting regulatory role diseases. goal this study was identify novel SHP-regulated genes that are involved the development chronic disease. To achieve this, we conducted first comprehensive RNA sequencing (RNA-seq) analysis Shp(-/-)...
Background Sessile serrated adenomas/polyps (SSA/Ps) may account for 20–30% of colon cancers. Although large SSA/Ps are generally recognized phenotypically, small (<1 cm) or dysplastic difficult to differentiate from hyperplastic adenomatous polyps by endoscopy and histopathology. Our aim was define the comprehensive gene expression phenotype better this cancer precursor. Results RNA sequencing performed on 5′ capped seven collected patients with polyposis syndrome (SPS) versus eight...
Abstract Sessile serrated colon adenoma/polyps (SSA/P) are found during routine screening colonoscopy and may account for 20% to 30% of cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk cancer is challenging complementary molecular markers needed. In addition, the mechanisms development poorly understood. RNA sequencing (RNA-Seq) was performed on 21 SSA/Ps, 10 HPs, adenomas, uninvolved colon, 20 control specimens. Differential expression leave-one-out...
The receptor for advanced glycation end products (RAGE), a cell membrane receptor, recognizes ligands produced by cigarette smoke (CS) and has been implicated in the pathogenesis of COPD. We demonstrate that deletion or pharmacologic inhibition RAGE prevents development CS-induced emphysema. To identify molecular pathways which mediates smoking related lung injury we performed unbiased gene expression profiling alveolar macrophages (AM) obtained from null C57BL/6 WT mice exposed to CS one...
Conazoles are environmental and pharmaceutical fungicides. The present study relates the toxicological effects of conazoles to alterations gene pathway transcription identifies potential modes tumorigenic action. In a companion employing conventional bioassays (Allen et al., 2006), male CD-1 mice were fed triadimefon, propiconazole, or myclobutanil in continuous oral-dose regimen for 4, 30, 90 days. These found induce hepatomegaly, high levels hepatic pentoxyresorufin-O-dealkylase activity,...
We describe the first report of RNA sequencing 5' capped (Pol II) RNAs isolated from acutely hepatitis C virus (HCV) infected Huh 7.5 cells that provides a general approach to identifying differentially expressed annotated and unannotated genes participate in viral-host interactions. identified 100, 684, 1,844 significantly proliferative at 6, 48, 72 hours, respectively (fold change ≥ 1.5 Bonferroni adjusted p-values < 0.05). Most (>80%) biological pathways (such as adipocytokine,...
Gene expression-based profiling of colorectal cancer (CRC) can be used to identify four molecularly homogeneous consensus molecular subtype (CMS) groups with unique biologic features. However, its applicability premalignant lesions remains unknown.We assembled the largest transcriptomic premalignancy dataset by integrating different public and proprietary cohorts adenomatous serrated polyps from sporadic (N = 311) hereditary 78) patient populations carried out a comprehensive analysis...
The use of assisted reproductive technologies (ART) has enabled the birth over 9 million babies; but it is associated with increased risks negative metabolic outcomes in offspring. Yet, underlying mechanism remains unknown. Calcium (Ca2+) signals, which initiate embryo development at fertilization, are frequently disrupted human ART. In mice, abnormal Ca2+ signals fertilization impair and adult offspring metabolism. Changes intracellular drive mitochondrial activity production metabolites...
Abstract Background The information content within nucleic acids extends beyond the primary sequence to include secondary structures with functional roles in transcription regulation. Guanine-rich sequences form called guanine quadruplexes that result from non-canonical base pairing between residues. These stable quadruplex are prevalent gene promoters nuclear DNA and known be associated promoter proximal pausing of some genes. However, transcriptional impact nascent RNA is poorly...
Background Differences in responses to environmental chemicals and drugs between life stages are likely due part differences the expression of xenobiotic metabolizing enzymes transporters (XMETs). No comprehensive analysis mRNA XMETs has been carried out through any species. Results Using full-genome arrays, all their regulatory proteins was examined during fetal (gestation day (GD) 19), neonatal (postnatal (PND) 7), prepubescent (PND32), middle age (12 months), old (18 24 months) C57BL/6J...
Alcohol-associated liver disease (ALD) represents a spectrum of histopathological changes, including alcoholic steatosis, steatohepatitis, and cirrhosis. One the early responses to excessive alcohol consumption is lipid accumulation in hepatocytes. Lipid ω-hydroxylation medium- long-chain fatty acid metabolized by cytochrome P450 4A (CYP4A) family an alternative pathway for metabolism. The molecular mechanisms CYP4A ALD pathogenesis have not been elucidated. In this study, WT Shp−/− mice...
To identify gene expression biomarkers and pathways targeted by sulindac erlotinib given in a chemoprevention trial with significant decrease duodenal polyp burden at 6 months (
Serrated polyposis syndrome (SPS) presents with multiple sessile serrated lesions (SSL) in the large intestine and confers increased colorectal cancer (CRC) risk. However, etiology of SPS is not known. SSL-derived organoids have been previously studied but may help provide insights into pathogenesis identify novel biomarkers chemopreventive strategies. This study examined effects EGFR COX pathway inhibition organoid cultures derived from uninvolved colon polyps patients. We also compared...