A5013040974- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- Genomics, phytochemicals, and oxidative stress
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- RNA modifications and cancer
- TGF-β signaling in diseases
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Molecular Biology Techniques and Applications
- Cervical Cancer and HPV Research
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Cancer, Lipids, and Metabolism
- Colorectal Cancer Treatments and Studies
- Bioactive Compounds and Antitumor Agents
- Diet and metabolism studies
- Bioinformatics and Genomic Networks
- Ferroptosis and cancer prognosis
- Ion channel regulation and function
- Microtubule and mitosis dynamics
University of South Carolina
2016-2025
The University of Texas Health Science Center at San Antonio
2018
University of Alabama at Birmingham
2014-2015
Immunovaccine (Canada)
2014
Augusta University Health
2012-2013
Augusta University
2007-2012
Johns Hopkins University
1998-2007
Vavilov Institute of General Genetics
2007
University Hospitals of Cleveland
2006-2007
Case Western Reserve University
2006-2007
The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers unprecedented detail. To begin a systematic analysis such alterations, we determined well-annotated protein-coding genes two common tumor types. Analysis 13,023 11 breast and colorectal revealed that individual tumors accumulate an average approximately 90 mutant but only subset these contribute neoplastic process. Using stringent criteria delineate this subset, identified 189...
Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast colorectal tumors determined sequences genes Reference Sequence database these samples. Based on analysis exons representing 20,857 transcripts 18,191 genes, conclude genomic landscapes cancers are composed a handful commonly mutated gene "mountains" much larger number "hills" at low frequency. We describe...
Mounting evidence indicates that Smad proteins are required for TGFβ signaling, but the way(s) in which propagate this signal is unclear. We found two human (Smad3 and Smad4) could specifically recognize an identical 8 bp palindromic sequence (GTCTAGAC). Tandem repeats of palindrome conferred striking responsiveness to a minimal promoter. This was abrogated by targeted deletion cellular Smad4 gene. These results define novel biochemical property likely play direct role biologic responses...
To gain insights into the molecular basis for metastasis, we compared global gene expression profile of metastatic colorectal cancer with that primary cancers, benign tumors, and normal epithelium. Among genes identified, PRL-3 protein tyrosine phosphatase was particular interest. It expressed at high levels in each 18 metastases studied but lower nonmetastatic tumors In 3 12 examined, multiple copies were found within a small amplicon located chromosome 8q24.3. These data suggest is...
Abstract Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as key inducer of chemoresistance by developing chemoresistant TNBC tumors vivo and characterizing their transcriptomes RNA-sequencing. Inhibiting LOX reduces collagen cross-linking fibronectin assembly, increases drug penetration, downregulates ITGA5/FN1 expression, resulting inhibition FAK/Src signaling,...
Abstract Purpose: Patients with pancreatic ductal adenocarcinoma usually present advanced-stage disease and a dismal prognosis. One effective strategy likely to improve the morbidity mortality from cancer would be identification of accurate, noninvasive diagnostic markers that enable earlier diagnosis symptomatic patients detection in asymptomatic individuals at high risk for developing cancer. In this study, we evaluated serum macrophage inhibitory cytokine-1 (MIC-1) as marker Experimental...
Summary Microphthalmia‐associated transcription factor (MITF) is involved in melanocyte cell development, pigmentation and neoplasia. To determine whether MITF somatically mutated melanoma, we compared the sequence of from primary metastatic lesions to patient‐matched normal DNA. In 50 melanoma tumor lines analysed, discovered four samples that had genomic amplifications mutations regions encoding transactivation, DNA binding or basic, helix‐loop‐helix domains. Sequence analysis for SOX10 ,...
Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 E7 is thought to be necessary maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, most experimental specifically E6/E7. We investigated the presence in correlate oncogene with clinical molecular features these tumors that may relevant new targeted therapies.While virtually all cancers contained DNA, expressed E6/E7 (HPV-active), a subset (8%)...
Identifying genetic dependencies in human colon cancer could help identify effective treatment strategies. Genome-wide CRISPR-Cas9 dropout screens have the potential to reveal dependencies, some of which be exploited as therapeutic targets using existing drugs. In this study, we comprehensively characterized present a organoid avatar, and validated tumor-specific selectivity select pharmacologic agents. We conducted genome-wide CRISPR screen elucidate that interacted with driver somatic...
Smad4 (DPC4) is a candidate tumor suppressor gene that has been hypothesized to be critical for transmitting signals from transforming growth factor (TGF) beta and related ligands. To directly test this hypothesis, the was deleted through homologous recombination in human colorectal cancer cells. This deletion abrogated signaling TGF-beta, as well TGF-beta family member activin. These results provide unequivocal evidence mutational inactivation of causes unresponsiveness basis understanding...
Transformation of baby hamster kidney fibroblasts by the Rous sarcoma virus causes a significant increase in GlcNAcβ(1,6)Man-branched oligosaccharides elevating activity and mRNA transcript levels encoding<i>N</i>-acetylglucosaminyltransferase V (GlcNAc-T V). Elevated could be inhibited blocking cell proliferation with herbimycin A, demonstrating that Src kinase can regulate GlcNAc-T expression. 5′ RACE analysis was used to identify 3-kilobase 5′-untranslated region from locate...
A cDNA clone for the complete coding sequence alpha-1,3(6)-mannosylglycoprotein beta-1,6-N-acetylglucosaminyltransferase V (GlcNAc-T V, EC 2.4.1.155) was isolated and expressed in COS-7 cells. Degenerate oligonucleotide primers polymerase chain reaction were synthesized based on amino acid of three tryptic peptides from affinity-purified GlcNAc-T V. Polymerase amplimers rat mouse mRNA. cDNA-encoding full-length enzyme a 1 cell (EJ-ras-transformed) library sequenced. Transient expression this...
ErbB2/Neu oncogene is overexpressed in 25% of invasive/metastatic breast cancers. We have found that deletion heat shock factor Hsf1 mice overexpressing significantly reduces mammary tumorigenesis and metastasis. Hsf1(+/-)ErbB2/Neu(+) tumors exhibit reduced cellular proliferative invasive properties associated with activated ERK1/2 epithelial-mesenchymal transition (EMT). Hsf1(+/+)Neu(+) epithelial cells exposed to TGFβ show high levels activity EMT; this expression E-cadherin increased Slug...
Background BRAFV600 inhibitors have offered a new gateway for better treatment of metastatic melanoma. However, the overall efficacy has been lower than expected in clinical trials, and many patients shown resistance to drug's effect. We hypothesized that somatic mutations Phosphoinositide 3-Kinase (PI3K) pathway, which promotes proliferation survival, may coincide with contribute chemotherapeutic resistance. Methods performed mutation profiling study using 454 FLX pyrosequencing platform...
IL-10 functions as a suppressor of colitis and colitis-associated colon cancer, but it is also risk locus associated with ulcerative colitis. The mechanism underlying the contrasting roles in inflammation cancer unknown. We report here that induces accumulation CD11b+Gr1+ myeloid-derived cells (MDSCs) express high levels tissue. activation STAT3 directly binds to Dnmt1 Dnmt3b promoters activate their expression, resulting DNA hypermethylation at Irf8 promoter silence IRF8 expression...
Elevation of L-2-hydroxylgutarate (L-2-HG) in renal cell carcinoma (RCC) is due part to reduced expression L-2-HG dehydrogenase (L2HGDH). However, the contribution carcinogenesis and insight into biochemistry targets this small molecule remains be elucidated.Genetic pharmacologic approaches modulate levels were assessed for effects on vitro vivo phenotypes. Metabolomics was used dissect biochemical mechanisms that promote accumulation RCC cells. Transcriptomic analysis utilized identify...
Abstract Breast cancer is the most common and second leading cause of cancer-related death among women. An important risk factor for breast individual genetic background, which initially generated early in human life, example, during processes embryogenesis fetal development utero. Bioactive dietary components such as sulforaphane (SFN), an isothiocyanate from cruciferous vegetables including broccoli sprouts (BSp), cabbage, kale, has been shown to reduce developing many cancers through...
Metastatic dissemination of primary tumors is responsible for 90% colorectal cancer (CRC) deaths. The presence positive lymph nodes, which separates stage I/II from III CRC, a particularly key factor in patient management. Here, we describe results quantitative proteomic survey to identify molecular correlates node status. Laser capture microdissection and two-dimensional difference gel electrophoresis were used establish expression profiles 980 discrete protein features 24 human CRC...
Abstract Exome sequencing of human breast cancers has revealed a substantial number candidate cancer genes with recurring but infrequent somatic mutations. To determine more accurately their mutation prevalence, we performed analysis 36 novel in 96 cancers. Somatic mutations potential impact on protein function were observed the ADAM12 , CENTB1 CENTG1 DIP2C GLI1 GRIN2D HDLBP IKBKB KPNA5 NFKB1 NOTCH1, and OTOF . These findings strengthen evidence for involvement Notch, Hedgehog, NF‐KB, PIK3CA...
PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated PRDM1β p53-response gene human colorectal cancer cells. However, the function of cells colon organoids not clear. Here we show low expression predicts poor survival patients. We engineered knockouts overexpression clones RKO characterized PRDM1-dependent transcript landscapes, revealing both α β isoforms repress MYC-response genes stem cell-related genes. Finally, forced...