A5087237202- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Helicobacter pylori-related gastroenterology studies
- DNA Repair Mechanisms
- Digestive system and related health
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Cancer Cells and Metastasis
- Fungal and yeast genetics research
- RNA modifications and cancer
- Nutrition, Genetics, and Disease
- RNA Research and Splicing
- 14-3-3 protein interactions
- Acute Myeloid Leukemia Research
- Cancer Research and Treatments
- PARP inhibition in cancer therapy
- Blood disorders and treatments
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Virology and Viral Diseases
- Photosynthetic Processes and Mechanisms
- BRCA gene mutations in cancer
- Rabies epidemiology and control
The Ohio State University
2006-2018
The Ohio State University Wexner Medical Center
2010-2014
Thomas Jefferson University
2004-2011
Cancer Genetics (United States)
2007-2011
National Cancer Institute
2011
Brigham and Women's Hospital
2011
Albert Einstein College of Medicine
2011
Sidney Kimmel Cancer Center
2004
Queen's University Belfast
1994-2003
Belfast City Hospital
2003
Inactivation of mismatch repair (MMR) is the cause common cancer predisposition disorder Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal (HNPCC), well 10–40% sporadic colorectal, endometrial, ovarian, gastric, and urothelial cancers. Elevated mutation rates (mutator phenotype), including simple repeat instability [microsatellite (MSI)] are a signature MMR defects. MicroRNAs (miRs) have been implicated in control critical cellular pathways involved development cancer....
Abstract Oxidative DNA damage is unavoidably and continuously generated by oxidant byproducts of normal cellular metabolism. The repair genes, mutY mutM, prevent G to T mutations caused reactive oxygen species in Escherichia coli, but it has remained debatable whether deficiencies their mammalian counterparts, Myh Ogg1, are directly involved tumorigenesis. Here, we demonstrate that Ogg1 predispose 65.7% mice tumors, predominantly lung ovarian lymphomas. Remarkably, subsequent analyses...
DNA damage response (DDR) activates a complex signaling network that triggers repair, cell cycle arrest, and/or death. Depending on the type and severity of lesion, DDR is controlled by "master" regulators including ATM ATR protein kinases. Cisplatin, major chemotherapy drug cross-links DNA, induces ATR-dependent DDR, resulting in apoptosis. However, it unclear how activated. To identify key ATR, we analyzed proteins associate with after cisplatin treatment blue native-PAGE...
Abstract The septin family of genes has been implicated in a variety cellular processes including cytokinesis, membrane transport and fusion, exocytosis, apoptosis. One member the maps to chromosome 17q25.3, region commonly deleted sporadic ovarian breast tumours, also identified as fusion partner MLL acute myeloid leukaemias. present study demonstrates that pattern expression multiple splice variants this gene is altered tumours cell lines. In particular, zeta transcript detectable majority...
Reverse transcription of retroviral RNA genomes produce a double-stranded linear cDNA molecule. A host degradation system prevents majority the molecules from completing obligatory genomic integration necessary for pathogenesis. We demonstrate that human TFIIH complex proteins XPB (ERCC3) and XPD (ERCC2) play principal role in cDNA. DNA repair-deficient mutant cell lines exhibited an increase transduction efficiency by both HIV- Moloney murine leukemia virus-based vectors. Replicating virus...
Abstract Nonsteroidal anti–inflammatory drugs (NSAID) appear to be effective cancer chemopreventives. Previous cellular studies showed that aspirin (acetylsalicylic acid: ASA) and nitric oxide–donating ASA (NO-ASA) suppressed microsatellite instability (MSI) in mismatch repair (MMR)-deficient cells linked the common predisposition syndrome hereditary nonpolyposis colorectal or Lynch (LS/HNPCC), at doses 300- 3,000-fold less than ASA. Using a mouse model develops MMR-deficient intestinal...
Abstract Nitric oxide–donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as cancer chemopreventive agents. Aspirin and sulindac have been shown to be effective in selecting for cells reduced microsatellite instability (MSI) that is inherent mismatch repair (MMR)–deficient hereditary nonpolyposis colorectal (HNPCC) cells. The effect NO-NSAIDs on MSI MMR-deficient HNPCC unknown. Here, we examined genetically...
This paper corrects the previously published sequence of L gene canine distemper virus (CDV). Errors in (M. S. Sidhu et al., 1993, Virology 193, 50-65) led to frame shifts between residues 1021-1032, 1190-1219 and 1645-1650; a deletion 21 amino acids 1684-1705, single residue at 1478. Residue 237 is now found be glycine rather than tryptophan 1626 proline instead threonine. The phocine (PDV) was also determined. Alignment morbillivirus proteins showed that PDV CDV are more closely related...
Defects in coordinated ribosomal RNA (rRNA) transcription the nucleolus cause cellular and organismal growth deficiencies. Bloom’s syndrome, an autosomal recessive human disorder caused by mutated recQ-like helicase BLM, presents with defects suggestive of underlying rRNA transcription. Our previous studies showed that BLM facilitates interacts polymerase I topoisomerase (TOP1) nucleolus. The mechanisms regulating localization to are unknown. In this study, we identify TOP1-interaction...
APC biallelic loss-of-function mutations are the most prevalent genetic changes in colorectal tumors, but it is unknown whether these phenocopy gain-of-function CTNNB1 gene encoding β-catenin that also activate canonical WNT signaling. Here we demonstrate two mutational mechanisms not equivalent. Furthermore, show how differences expression produced by different can stratify outcomes more advanced human cancers. Gene profiling Apc-mutant and Ctnnb1-mutant mouse colon adenomas identified...
Although disruption of DNA repair capacity is unquestionably associated with cancer susceptibility in humans and model organisms, it remains unclear if the inherent tumor phenotypes deficiency syndromes can be regulated by manipulating pathways. Loss-of-function mutations BLM, a member RecQ helicase family, cause Bloom's syndrome (BS), rare, recessive genetic disorder that predisposes to many types cancer. BLM functions aspects homeostasis, including suppression homologous recombination (HR)...
Abstract The role of genomic instability in colorectal cancer susceptibility is well established by studies hereditary non-polyposis colon (HNPCC), its associated disruption DNA mismatch repair, and other repair deficiencies that predispose to cancer. deficiency results loss capacity maintain the genome leads increased mutation or chromosome turn increases tumor formation. In some recent experiments using mouse models cancer, deletion housekeeping genes promoted tumorigenesis. Blm gene...
<p>Supplementary Figure S1. qPCR discriminates between mice hemizygous and homozygous for the BLM-Tg.</p>
Supplementary Methods, Tables, and Figures from Aspirin Low-Dose Nitric Oxide–Donating Increase Life Span in a Lynch Syndrome Mouse Model
<p>Supplementary Figure S1. qPCR discriminates between mice hemizygous and homozygous for the BLM-Tg.</p>
<div>Abstract<p>Nonsteroidal anti–inflammatory drugs (NSAID) appear to be effective cancer chemopreventives. Previous cellular studies showed that aspirin (acetylsalicylic acid: ASA) and nitric oxide–donating ASA (NO-ASA) suppressed microsatellite instability (MSI) in mismatch repair (MMR)-deficient cells linked the common predisposition syndrome hereditary nonpolyposis colorectal or Lynch (LS/HNPCC), at doses 300- 3,000-fold less than ASA. Using a mouse model develops...
<div>Abstract<p>Nonsteroidal anti–inflammatory drugs (NSAID) appear to be effective cancer chemopreventives. Previous cellular studies showed that aspirin (acetylsalicylic acid: ASA) and nitric oxide–donating ASA (NO-ASA) suppressed microsatellite instability (MSI) in mismatch repair (MMR)-deficient cells linked the common predisposition syndrome hereditary nonpolyposis colorectal or Lynch (LS/HNPCC), at doses 300- 3,000-fold less than ASA. Using a mouse model develops...
<div>Abstract<p>Although disruption of DNA repair capacity is unquestionably associated with cancer susceptibility in humans and model organisms, it remains unclear if the inherent tumor phenotypes deficiency syndromes can be regulated by manipulating pathways. Loss-of-function mutations <i>BLM</i>, a member <i>RecQ</i> helicase family, cause Bloom's syndrome (BS), rare, recessive genetic disorder that predisposes to many types cancer. BLM functions...
Abstract Mutation of the APC tumor suppressor gene occurs in approximately 75% colorectal cancers (CRC) and is considered central event driving initiation large intestine. The protein controls expression indirectly through canonical WNT signaling pathway as a component cytoplasmic complex that promotes proteolysis transcriptional co-regulator β-catenin. Recent studies have shown also chromatin-associated interacts with promoter MYC proto-oncogene to downregulate its transcription. We tested...
<p>Correlations between overexpression of MAP6, MSRB3 or PXDC1 in human colorectal tumors and shorter disease-free survival do not validate the TCGA dataset.</p>