A5024242252- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Multiple Myeloma Research and Treatments
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Circular RNAs in diseases
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- RNA Research and Splicing
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Childhood Cancer Survivors' Quality of Life
- Renal and related cancers
- Cancer survivorship and care
- Prostate Cancer Treatment and Research
- Wnt/β-catenin signaling in development and cancer
- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
University of Rochester
2019-2025
University of Rochester Medical Center
2019-2024
Emory University
2014-2023
Molecular Oncology (United States)
2008-2016
Radiation Oncology Associates
2015
Piedmont Cancer Institute
2008-2014
Winship Cancer Institute
2002-2014
Johns Hopkins University
1993-2014
Sidney Kimmel Comprehensive Cancer Center
2014
Atlanta VA Medical Center
2014
CRISPR/Cas9 systems are a versatile tool for genome editing due to the highly efficient targeting of DNA sequences complementary their RNA guide strands. However, it has been shown that RNA-guided Cas9 nuclease cleaves genomic containing mismatches strand. A better understanding specificity is needed minimize off-target cleavage in large mammalian genomes. Here we show sites could be cleaved by when contain insertions (‘DNA bulge’) or deletions (‘RNA compared strand, and nickases used paired...
Cytosine residues in mammalian DNA occur at least three forms, cytosine (C), 5-methylcytosine (M; 5mC) and 5-hydroxymethylcytosine (H; 5hmC). During semi-conservative replication, hemi-methylated (M/C) hemi-hydroxymethylated (H/C) CpG dinucleotides are transiently generated, where only the parental strand is modified daughter contains native cytosine. Here, we explore role of methyltransferases (DNMT) ten eleven translocation (Tet) proteins perpetuating these states after molecular basis...
Abstract Withaferin A (WFA) is purified from the plant Withania somnifera and inhibits vimentin cytoskeleton. Vimentin overexpression in cancer correlates with metastatic disease, induction of epithelial to mesenchymal transition reduced patient survival. As functions cell motility, we wanted test hypothesis that WFA metastasis by disrupting function. These data showed had weak cytotoxic apoptotic activity at concentrations less than or equal 500 nM, but retained potent anti‐invasive these...
Although human LINE-1 (L1) elements are actively mobilized in many cancers, a role for somatic L1 retrotransposition tumor initiation has not been conclusively demonstrated. Here, we identify novel insertion the APC suppressor gene that provided us with unique opportunity to determine whether such insertions can actually initiate colorectal cancer (CRC), and if so, how this might occur. Our data support model whereby hot source element on Chromosome 17 of patient's genome evaded repression...
Abstract Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms poorly understood. We report that bone-borne TGF-β induces acetylation of transcription factor KLF5 in PCa metastases, acetylated (Ac-KLF5) causes osteoclastogenesis metastatic lesions by activating CXCR4, leads to IL-11 secretion, stimulating SHH/IL-6 paracrine signaling. While essential maintaining mesenchymal phenotype tumorigenicity, Ac-KLF5 also...
Molecular changes during progressive stages of colon cancer and other human tumors commonly involve altered regulation DNA methylation. These include overall genomic hypomethylation, regional hypermethylation, increased levels messenger RNA (mRNA) for cytosine DNA-methyltransferase (DNA-MTase), the enzyme that catalyzes methylation at CpG (cytosine-phospho-guanine) sites. This increase in DNA-MTase transcripts (mRNA), if accompanied by activity, could play a role abnormal patterns appear...
Recent studies showing a correlation between the levels of DNA (cytosine-5-)-methyltransferase (DNA MTase) enzyme activity and tumorigenicity have implicated this in carcinogenic process. Moreover, hypermethylation CpG island-containing promoters is associated with inactivation genes important to tumor initiation progression. One proposed role for MTase tumorigenesis therefore direct de novo methylation these otherwise unmethylated islands. In study, we sought determine whether increased...
Epigenetic silencing associated with aberrant methylation of promoter region CpG islands is one mechanism leading to loss tumor suppressor function in human cancer. Profiling island indicates that some genes are more frequently methylated than others, and each type a unique set genes. However, little known about why certain succumb this event. To address question, we used Restriction Landmark Genome Scanning analyze the susceptibility 1,749 unselected de novo driven by overexpression DNA...
We have previously linked aging, carcinogenesis, and de novo methylation within the promoter of estrogen receptor (ER) gene in human colon. now examine dynamics this process for imprinted insulin-like growth factor II (IGF2). In young individuals, P2-4 promoters IGF2 are methylated exclusively on silenced maternal allele. During becomes more extensive involves originally unmethylated Most adult tumors, including colon, breast, lung, leukemias, exhibit increased at promoters, suggesting...
DNA methylation plays a crucial role in the regulation of gene expression and chromatin organization within normal eukaryotic cells. In cancer, however, global patterns are altered with hypomethylation repeat-rich intergenic regions hypermethylation subset CpG-dense gene-associated (CpG islands). Extensive research has revealed cellular machinery that catalyzes methylation, as well several large protein complexes mediate transcriptional repression hypermethylated genes. However, is only just...
Journal Article Isolation and characterization of the cDNA encoding human DNA methyltransferase Get access Ray-Whay Chiu Yen, Yen 1Oncology CenterLivermore, CA 94551, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Paula M. Vertino, Vertino Barry D. Nelkin, Nelkin Jane J. Yu, Yu Wafik El-Deiry, El-Deiry Arunthathi Cumaraswamy, Cumaraswamy Gregory G. Lennon, Lennon 3Human Genome Center, Biomedical Sciences Division, The Lawrence Livermore National...
Numerous epidemiological studies documented that obesity is a risk factor for breast cancer development in postmenopausal women. Leptin, the key player regulation of energy balance and body weight control also acts as growth on certain organs both normal disease state. In this study, we analyzed role leptin molecular mechanism(s) underlying its action cells express short long isoforms receptor. Leptin increased MCF7 cell population S-phase cycle along with robust increase CYCLIN D1...
Abstract Breast tumors expressing estrogen receptor-α (ER) respond well to therapeutic strategies using selective ER modulators, such as tamoxifen. However, ∼30% of invasive breast cancers are hormone independent because they lack expression due hypermethylation promoter. Treatment ER-negative cancer cells with demethylating agents [5-aza-2′-deoxycytidine (5-aza-dC)] and histone deacetylase (HDAC) inhibitors (trichostatin A) leads mRNA functional protein. Here, we examined whether...
Monoallelic point mutations of the NADP + -dependent isocitrate dehydrogenases IDH1 and IDH2 occur frequently in gliomas, acute myeloid leukemias, chondromas, display robust association with specific DNA hypermethylation signatures. Here we show that heterozygous expression R132H allele is sufficient to induce genome-wide alterations methylation characteristic these tumors. Using a gene-targeting approach, knocked-in single copy most observed mutation, R132H, into human cancer cell line...
An increase in the risk of cancer is one consequences obesity. The predominant cancers associated with obesity have a hormonal basis and include breast, prostate, endometrium, colon gall-bladder cancers. Leptin, key player regulation energy balance body weight control also acts as growth factor on certain organs both normal disease states. Therefore, it plausible that leptin to promote by acting mitogenic agent. However, direct role for endometrial has not been demonstrated. In this study,...
Abstract Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% relapse or die within two years and are deemed high risk. Here we analyze structural variants 795 newly-diagnosed as part the CoMMpass study. We report translocations involving immunoglobulin lambda (IgL) locus present in 10% patients, indicative poor prognosis. This particularly true for IgL-MYC translocations, which coincide with focal amplifications...
Abstract Phenotypic heterogeneity is widely observed in cancer cell populations. Here, to probe this heterogeneity, we developed an image-guided genomics technique termed spatiotemporal genomic and cellular analysis (SaGA) that allows for precise selection amplification of living rare cells. SaGA was used on collectively invading 3D packs create purified leader follower lines. The cultures are phenotypically stable highly invasive contrast cultures, which show phenotypic plasticity over time...