A5033341714- Neurofibromatosis and Schwannoma Cases
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Heat shock proteins research
- Chromatin Remodeling and Cancer
- Prostate Cancer Treatment and Research
- Cancer Mechanisms and Therapy
- Cancer, Lipids, and Metabolism
- Microtubule and mitosis dynamics
- Estrogen and related hormone effects
- Renin-Angiotensin System Studies
- Ear and Head Tumors
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Biomedical Text Mining and Ontologies
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- ATP Synthase and ATPases Research
- Hormonal and reproductive studies
- Computational Drug Discovery Methods
- Surface Treatment and Residual Stress
- Adrenal and Paraganglionic Tumors
Weatherford College
2023
Laboratoire d’immunologie intégrative du cancer
2023
LabCorp (United States)
2019-2022
Cincinnati Children's Hospital Medical Center
2007-2019
University of Cincinnati
2007-2019
Covance (United States)
2011-2015
Peter MacCallum Cancer Centre
2013
University of Southern California
2013
University of California, Los Angeles
2013
Inserm
2013
Abstract Background The expression of carcino-embryonic antigen by colorectal cancer is an example oncogenic activation embryonic gene expression. Hypothesizing that oncogenesis-recapitulating-ontogenesis may represent a broad programmatic commitment, we compared patterns human cancers (CRCs) and mouse colon tumor models to those development days 13.5-18.5. Results We report here 39 tumors from four independent 100 CRCs encompassing all clinical stages shared striking recapitulation Compared...
Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated controls numerous downstream effectors, but specific pathways mediating the effects in are unknown. We performed cross-species transcriptome analyses mouse human MPNSTs identified global negative feedback genes that regulate Ras/Raf/MEK/ERK signaling both...
Abstract To identify biomarkers that discriminate the aggressive forms of prostate cancer, we performed gene expression profiling tumors using a genetically engineered mouse model recapitulates stages human namely Nkx3.1; Pten mutant mice. We observed significant deregulation epidermal growth factor and mitogen-activated protein kinase (MAPK) signaling pathways, as well their major downstream effectors—the activator protein-1 transcription factors c-Fos c-Jun. Forced c-Jun in cancer cells...
Research Article10 July 2009Open Access Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene Shyra J. Miller Divisions Experimental Hematology Cancer Biology, Cincinnati Children's Hospital, University College Medicine, Cincinnati, OH, USA Contributed equally to this work. Search for more papers by author Walter Jessen Biomedical Informatics, Hospital Foundation, Tapan Mehta Department Biostatistics, Section on Statistical Genetics, Alabama...
Abstract The genetic evolution from a benign neurofibroma to malignant sarcoma in patients with neurofibromatosis type 1 (NF1) syndrome remains unclear. Schwann cells and/or their precursor are believed be the primary pathogenic cell neurofibromas because they harbor biallelic neurofibromin gene mutations. However, phosphatase and tensin homolog (Pten) (Nf1) genes recently were found comutated high-grade peripheral nerve sheath tumors (PNST) mice. In this study, we created transgenic mice...
Abstract In this report, we have investigated the relationship between androgen levels and prostate tumorigenesis in Nkx3.1; Pten mutant mice, a genetically engineered mouse model of human cancer. By experimentally manipulating serum testosterone these mice for an extended period (i.e., 7 months), found that prolonged exposure to are 10-fold lower than normal (the “Low-T” group) resulted marked acceleration compared with those exposed within reference range “Normal-T” group). We tumors from...
Abstract Factors that drive prostate cancer progression remain poorly defined, thus hindering the development of new therapeutic strategies. Disseminated tumors are treated through regimens ablate androgen signaling, as cells require for growth and survival. However, recurrent, incurable have bypassed requirement ultimately arise. This study reveals Brm ATPase, a component selected SWI/SNF complexes, has significant antiproliferative functions in protect against these transitions. First, we...
Patients with neurofibromatosis type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNST), which are often inoperable and do not respond well to current chemotherapies or radiation. The goal of this study was use comprehensive gene expression analysis identify novel therapeutic targets.Nerve Schwann cells and/or their precursors the tumorigenic cell types in MPNST because loss NF1 gene, encodes RasGAP protein neurofibromin. Therefore, we created a transgenic mouse model,...
To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, molecular analyses. We mapped an Nf1-Stat3-Arid1b/β-catenin pathway becomes active in the context of Nf1 loss. Genetic deletion Stat3 Schwann cell progenitors (SCPs) cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal β-catenin activity. expression rescues effects loss SCPs. Importantly, P-STAT3 correlate...
D-type cyclins regulate cellular outcomes in part through cyclin-dependent, kinase-independent mechanisms that modify transcription factor action, and recent vivo studies showed cyclin D1 associates with a large number of transcriptional regulators cells the retina breast. Given frequency alterations cancer, it is imperative to delineate molecular by which controls key networks human disease. Prostate cancer was used as paradigm because this tumor type reliant at all stages disease on...
Abstract Purpose: The growth and survival of neurofibromatosis type 2 (NF2)–deficient cells are enhanced by the activation multiple signaling pathways including ErbBs/IGF-1R/Met, PI3K/Akt, Ras/Raf/Mek/Erk1/2. chaperone protein HSP90 is essential for stabilization these molecules. aim study was to characterize effect inhibition in various NF2-deficient models. Experimental Design: We tested efficacy small-molecule NXD30001, which has been shown be a potent inhibitor. antiproliferative...
Plexiform neurofibroma is a major contributor to morbidity in patients with neurofibromatosis type I (NF1). Macrophages and mast cells infiltrate neurofibroma, data from mouse models implicate these leukocytes development. Antiinflammatory therapy targeting cell populations has been suggested as means prevent Here, we compare gene expression Nf1-mutant nerves, which invariably form show disruption of neuron–glial interactions immune infiltration models, rarely progresses or without...
Abstract Purpose: Plexiform neurofibromas (pNF) are Schwann cell tumors found in a third of individuals with neurofibromatosis type 1 (NF1). pNF can undergo transformation to malignant peripheral nerve sheath (MPNST). There no identified serum biomarkers tumor burden or MPNST. Serum would be useful verify NF1 diagnosis, monitor burden, and/or detect transformation. Experimental Design: We used microarray gene expression analysis define 92 genes that encode putative secreted proteins...
Abstract Background Transcriptional modules (TM) consist of groups co-regulated genes and transcription factors (TF) regulating their expression. Two high-throughput (HT) experimental technologies, gene expression microarrays Chromatin Immuno-Precipitation on Chip (ChIP-chip), are capable producing data informative about regulatory mechanism a genome scale. The optimal approach to joint modeling generated by these two complementary biological assays, with the goal identifying characterizing...
We report a technique, named targeted gene methylation (TAGM), for identifying in vivo protein-binding sites chromatin. M. Cvi PI, cytosine-5 DNA methyltransferase recognizing GC sites, is fused to DNA-binding factor enabling simultaneous detection of methylation, footprints, and chromatin structural changes by bisulfite genomic sequencing. Using TAGM with the yeast transactivator Pho4, enrichments up 34- fold occur proximal native Pho4-binding sites. Additionally, significant selective...
Purpose: Alternations in gene methylation and other epigenetic changes regulate normal development as well drive disease progression. The aim of this study is to investigate global the buccal cells smokers smokeless tobacco users.Materials methods: Generally healthy adult male subjects were recruited into smoker (SMK), moist snuff consumer (MSC) non-tobacco (NTC) cohorts (40 subjects/cohort) (ClinicalTrials.gov Identifier: NCT01923402). Global profiling was performed on Illumina 450 K arrays...
Abstract Biomedical knowledge is growing exponentially; however, meta-knowledge around the data often lacking. PubMed a database comprising more than 21 million citations for biomedical literature from MEDLINE and additional life science journals dating back to 1950s. To explore use frequency of biomarkers across human disease, we mined biomarker-disease associations. We then ranked top 100 linked diseases by relevance mapped them medical subject headings (MeSH) and, subsequently, Disease...
Biomedical knowledge is growing exponentially; however, meta-knowledge around the data often lacking. PubMed a database comprising more than 21 million citations for biomedical literature from MEDLINE and additional life science journals dating back to 1950s. To explore use frequency of biomarkers across human disease, we mined biomarker-disease associations. We then ranked top 100 linked diseases by relevance mapped them medical subject headings (MeSH) and, subsequently, Disease Ontology....
Biomedical knowledge is growing exponentially; however, meta-knowledge around the data often lacking. PubMed a database comprising more than 21 million citations for biomedical literature from MEDLINE and additional life science journals dating back to 1950s. To explore use frequency of biomarkers across human disease, we mined biomarker-disease associations. We then ranked top 100 linked diseases by relevance mapped them medical subject headings (MeSH) and, subsequently, Disease Ontology....