A5076293102- Epigenetics and DNA Methylation
- Bladder and Urothelial Cancer Treatments
- RNA modifications and cancer
- Cancer-related gene regulation
- Urinary and Genital Oncology Studies
- Genomics and Chromatin Dynamics
- Renal and related cancers
- Renal cell carcinoma treatment
- MicroRNA in disease regulation
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Genetic Syndromes and Imprinting
- Ferroptosis and cancer prognosis
- Genetics and Neurodevelopmental Disorders
- Prostate Cancer Treatment and Research
- Urological Disorders and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Colorectal Cancer Treatments and Studies
- Prostate Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- melanin and skin pigmentation
- Immunotherapy and Immune Responses
University of Southern California
2016-2025
Southern California University for Professional Studies
1999-2024
Keck Hospital of USC
2024
USC Norris Comprehensive Cancer Center
2009-2023
Van Andel Institute
2022
Zhejiang Hospital
2019
Hangzhou Normal University
2014
Sidney Kimmel Comprehensive Cancer Center
2013
LAC+USC Medical Center
2010-2011
Tochigi Cancer Center
2010
DNA methylation in mammals is required for embryonic development, X chromosome inactivation and imprinting. Previous studies have shown that patterns become abnormal malignant cells may contribute to tumorigenesis by improper de novo silencing of the promoters growth-regulatory genes. RNA protein levels methyltransferase DNMT1 been be elevated tumors, however murine stem lacking Dnmt1 are still able methylate viral DNA. The recent cloning a new family methyltransferases (Dnmt3a Dnmt3b) mouse...
Abstract DNA methylation, histone modifications, and nucleosomal occupancy collaborate to cause silencing of tumor-related genes in cancer. The development drugs that target these processes is therefore important for cancer therapy. Inhibitors methylation deacetylation have been approved by the Food Drug Administration treatment hematologic malignancies. However, other mechanisms still need be developed. Recently, 3-deazaneplanocin A (DZNep) was reported selectively inhibit trimethylation...
We used mouse embryonic stem (ES) cells with systematic gene knockouts for DNA methyltransferases to delineate the roles of methyltransferase 1 (Dnmt1) and Dnmt3a -3b in maintaining methylation patterns genome. Dnmt1 alone was able maintain most CpG-poor regions analyzed. In contrast, both and/or Dnmt3b were required a select class sequences which included abundant murine LINE-1 promoters. novel hemimethylation assay show that even wild-type these contain high levels hemimethylated DNA,...
Almost 1-2% of the human genome is located within 500 bp either side a transcription initiation site, whereas far larger proportion (≈25%) potentially transcribable by elongating RNA polymerases. This observation raises question how packaged into chromatin to allow start sites be recognized regulatory machinery at same time as initiation, but not elongation, blocked in 25% intragenic DNA. We developed scanning technique called ChAP, coupling immunoprecipitation assay with arbitrarily primed...
DNA methylation and nucleosome positioning work together to generate chromatin structures that regulate gene expression. Nucleosomes are typically mapped using nuclease digestion requiring significant amounts of material varying enzyme concentrations. We have developed a method (NOMe-seq) uses GpC methyltransferase (M.CviPI) next generation sequencing high resolution footprint genome-wide less than 1 million cells while retaining endogenous information from the same strand. Using novel...
The Polycomb Repressive Complex 2 (PRC2) mediates epigenetic gene silencing by trimethylating histone H3 lysine 27 (H3K27me3) and is known to aberrantly silence tumor suppressor genes in cancer. EZH2, the catalytic subunit of PRC2, enhances tumorigenesis commonly overexpressed several types Our microRNA profiling bladder transitional cell carcinoma (TCC) patient samples revealed that microRNA-101 (miR-101) down-regulated TCC, we showed miR-101 inhibits proliferation colony formation TCC...
Epigenetic reprogramming is commonly observed in cancer, and hypothesized to involve multiple mechanisms, including DNA methylation Polycomb repressive complexes (PRCs). Here we devise a new experimental analytical strategy using customized high-density tiling arrays investigate coordinated patterns of gene expression, methylation, marks which differentiate prostate cancer cells from their normal counterparts. Three major changes the epigenomic landscape distinguish two cell types....
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...
Significance Our work shows a remarkable synergy between physiological levels of vitamin C and 5-aza-CdR. The combination enhances the viral mimicry response to DNA methyltransferase inhibitors, including upregulation endogenous retroviruses in dsRNA form induction defense pathways. Because patients with hematological other cancers are often markedly deficient, addition treatment protocols may be straightforward way increase clinical efficacy such drugs myelodysplastic syndrome leukemia.
Significance We examined recent whole-genome data of 53 organisms and found that the substantial differences in their genome sizes can be largely explained by proportion transposable elements (TEs) within them. TEs coexist with host because CpG methylation suppresses transcription. Genome expansion is therefore dependent to a large extent on action DNA methyltransferases, which evolved at roughly same time as TEs. A long-term outcome an increase C-to-T transition mutations both DNA, leads...
During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Recently, we reported that zebularine [1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one] acts as an inhibitor of exhibits chemical stability minimal cytotoxicity both vitro vivo. Here show continuous application to T24 cells induces maintains p16 gene expression sustains demethylation the 5' region for over 40 days, preventing remethylation. In...
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 The major goal of epigenetic therapy is to reverse aberrant promoter hypermethylation and restore normal function tumor suppressor genes by the use chromatin-modifying drugs. Decitabine, or 5-aza-2′-deoxycytidine (5-aza-CdR), a well-characterized drug that now Food Drug Administration approved for treatment myelodysplastic syndrome. Although 5-aza-CdR an extremely potent inhibitor DNA methylation, it subject degradation hydrolytic cleavage deamination cytidine deaminase. We show...