A5069976362- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- Wnt/β-catenin signaling in development and cancer
- Genetics and Neurodevelopmental Disorders
- Extracellular vesicles in disease
- Genetic Syndromes and Imprinting
- MicroRNA in disease regulation
- Kruppel-like factors research
- Estrogen and related hormone effects
- Circular RNAs in diseases
- Medical Imaging Techniques and Applications
- Peroxisome Proliferator-Activated Receptors
- Inflammatory mediators and NSAID effects
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer Genomics and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
- Renal and related cancers
- Cardiovascular Disease and Adiposity
- Cancer Cells and Metastasis
- Biofuel production and bioconversion
- Nutrition, Genetics, and Disease
- Diet and metabolism studies
- Tannin, Tannase and Anticancer Activities
Foundation for the National Institutes of Health
2025
National Cancer Institute
2024
Center for Cancer Research
2024
University of Missouri–St. Louis
2017-2020
National Institute of Nursing Research
2020
National Institutes of Health
2020
University of Utah
2004-2012
Huntsman Cancer Institute
2004-2010
The roles of DNA methyltransferase-2 (DNMT2) enzymes are controversial; whether DNMT2 functions primarily as a nuclear methyltransferase or cytoplasmic tRNA methyltransferase, and activity impacts development, dnmt2 mutant mice Drosophila lack phenotypes. Here we show that morpholino knockdown Dnmt2 protein in zebrafish embryos confers differentiation defects particular organs, including the retina, liver, brain. Importantly, proper organ required cytoplasm, not nucleus. Furthermore,...
DNA methylation and histone are two key epigenetic modifications that help govern heterochromatin dynamics. The roles for these chromatin-modifying activities in directing tissue-specific development remain largely unknown. To address this issue, we examined the of methyltransferase 1 (Dnmt1) H3K9 Suv39h1 zebra fish development. Knockdown Dnmt1 embryos caused defects terminal differentiation intestine, exocrine pancreas, retina. Interestingly, not all tissues required Dnmt1, as liver...
Although DNA methylation is critical for proper embryonic and tissue-specific development, how different methyltransferases affect development their targets remains unknown. We address this issue in zebrafish through antisense-based morpholino knockdown of Dnmt3 Dnmt1. Our data reveal that required neurogenesis, its absence results profound defects brain retina. Interestingly, other organs such as intestine remain unaffected suggesting requirements Dnmt3. Further, comparison Dnmt1 phenotypes...
Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a factor implicated in stress responses, metabolic control, poised states, regulates normal pathologic function. Oct1HI cells colon small intestine co-express known markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with frequency of CD24LOCD44HI cancer-initiating cells. Reducing expression via RNAi...
Mutations in the adenomatous polyposis coli (APC) gene result uncontrolled proliferation of intestinal epithelial cells and are associated with earliest stages colorectal carcinogenesis. Cyclooxygenase-2 (COX-2) is elevated human cancers plays an important role tumorigenesis; however, mechanisms by which APC mutations increased COX-2 expression remain unclear. We utilized mutant zebrafish cancer to investigate how modulates expression. report that up-regulated because a deficiency retinoic...
Mutations in the APC (adenomatous polyposis coli) tumor suppressor gene cause uncontrolled proliferation and impaired differentiation of intestinal epithelial cells. Recent studies indicate that human colon adenomas carcinomas lack retinol dehydrogenases (RDHs) regulates expression RDHL. These data suggest a model wherein controls enterocyte by controlling retinoic acid production. However, importance mediating control normal development remains unclear. To examine relationship between...
Mutations in the human adenomatous polyposis coli (APC) gene are thought to initiate colorectal tumorigenesis. The tumor suppressor function of APC is attributed primarily its ability regulate WNT pathway by targeting destruction β-catenin. We report here a novel role for regulating degradation transcriptional co-repressor C-terminal-binding protein-1 (CtBP1) through proteasome-dependent process. Further, CtBP1 suppresses expression intestinal retinol dehydrogenases, which required retinoic...
Abstract Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene seem to underlie initiation of many colorectal carcinomas. Loss APC function results accumulation β-catenin and activation β-catenin/TCF–dependent transcription. Recent studies have implicated controlling retinoic acid biosynthesis during normal intestinal development through a WNT-independent mechanism. Paradoxically, however, previous found that dietary supplementation ApcMIN mice with failed abrogate adenoma...
Abstract Background: Although radiation is known to modulate immune responses, it remains challenging identify effective combinations of and immune-based therapies. Because tumor, immune, other cells release extracellular vesicles (EVs) continuously because those are composed lipid membrane-bound complexes proteins nucleic acids, we have developed a suite tools enable systematic subset characterization tumor EV subsets. Broadly speaking, these provide new, informative approach for...
Retinoic acid (RA) is a potent signaling molecule that plays important roles in multiple and diverse developmental processes. The contribution of retinoic to promoting the development differentiation vertebrate intestine factors regulate RA production gut remain poorly defined. Herein, we report novel retinol dehydrogenase, rdh1l, required for proper differentiation. rdh1l expressed ubiquitously during early but becomes restricted by 3 days postfertilization. Knockdown results robust...
Congenital hypertrophy/hyperplasia of the retinal pigmented epithelium is an ocular lesion found in patients harboring mutations adenomatous polyposis coli (APC) tumor suppressor gene. We report that Apc-deficient zebrafish display developmental abnormalities both lens and retina. Injection dominant-negative Lef reduced Wnt signaling but did not rescue differentiation defects. In contrast, treatment apc mutants with all-trans retinoic acid rescued defects had no apparent effect on lens....
Abstract Circulating RNAs have been investigated systematically for over 20 years, both as constituents of circulating extracellular vesicles (EVs) or, more recently, non‐EV RNA carriers, such exomeres and supermeres. The high level variability low reproducibility rate EV/extracellular (exRNA) results generated even on the same biofluids promoted several efforts to limit pre‐analytical by standardizing sample collection preparation, along with instrument validation, setup calibration....