A5068452445- RNA modifications and cancer
- Multiple Myeloma Research and Treatments
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- FOXO transcription factor regulation
- Viral-associated cancers and disorders
- Lymphoma Diagnosis and Treatment
- DNA Repair Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- Cell death mechanisms and regulation
- Cancer Treatment and Pharmacology
- Chronic Lymphocytic Leukemia Research
- Chemokine receptors and signaling
- Microtubule and mitosis dynamics
- Cancer Mechanisms and Therapy
- Parvovirus B19 Infection Studies
- Cytomegalovirus and herpesvirus research
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
Iowa State University
2017-2024
University of Iowa
2006-2016
Carver Bible College
2014
Purdue University West Lafayette
2008
The ARF tumor suppressor is a nucleolar protein that activates p53-dependent checkpoints by binding Mdm2, p53 antagonist.Despite persuasive evidence can bind and inactivate Mdm2 in the nucleoplasm, prevailing view exerts its growth-inhibitory activities from within nucleolus.We suggest primarily functions outside nucleolus provide it sequestered held inactive compartment phosphoprotein, nucleophosmin (NPM).Most cellular bound to NPM regardless of whether cells are proliferating or growth...
Abstract SARS-CoV-2 has exploded throughout the human population. To facilitate efforts to gain insights into biology and target virus therapeutically, it is essential have a roadmap of likely functional regions embedded in its RNA genome. In this report, we used bioinformatics approach, ScanFold, deduce local structural landscape genome with highest likelihood being functional. We recapitulate previously-known elements structure provide model for folding an frameshift signal. Our results...
Abstract Background Myc is a well known driver of lymphomagenesis, and Myc-activating chromosomal translocation the recognized hallmark Burkitt lymphoma, an aggressive form non-Hodgkin's lymphoma. We developed model that mimics this event by inserting mouse cDNA gene into immunoglobulin heavy chain locus, just upstream intronic Eμ enhancer. These mice, designated iMyc , readily develop B-cell To study mechanism Myc-induced we analyzed signaling pathways in lymphoblastic lymphomas (LBLs) from...
The MYC proto-oncogene is a transcription factor implicated in broad range of cancers. regulated by several post-translational modifications including SUMOylation, but the functional impact this modification still unclear. Here, we report that SUMO E3 ligase PIAS1 SUMOylates MYC. We demonstrate promotes, SUMOylation-dependent manner, phosphorylation at serine 62 and dephosphorylation threonine 58. These events reduce turnover, leading to increased transcriptional activity. Furthermore, find...
(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed (CT) are useful imaging modalities for evaluating tumor progression treatment responses in genetically engineered mouse models of solid human cancers, but the potential integrated FDG-PET/CT assessing development new interventions transgenic blood cancers such as multiple myeloma (MM) has not been demonstrated. Here we use BALB/c mice that contain newly developed iMyc(ΔEμ) gene insertion widely expressed H2-L(d)-IL6...
The ARF tumor suppressor protects us against cancer through protein-protein interactions in partially defined p53-dependent and p53-independent pathways. We performed a two-hybrid screen using as bait present the identification of several new partners that may regulate its growth inhibitory signaling. potential physiological roles these novel binding proteins regulating signaling are discussed.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by early recurrence following pancreatectomy, rapid progression, and chemoresistance. Novel prognostic predictive biomarkers are urgently needed to both stratify patients for clinical trials select adjuvant therapy regimens. This study sought determine the biological significance of RABL6A (RAB, member RAS oncogene family-like protein 6 isoform A), a novel pancreatic protein, in PDAC. Analyses expression PDAC specimens from 73 who...
The ARF tumor suppressor signals through p53 and other poorly defined anti-proliferative pathways to block carcinogenesis. In a search for new regulators of signaling, we discovered novel nuclear protein that named NIAM (nuclear interactor MDM2) its ability bind both the antagonist MDM2. is normally expressed at low undetectable levels in cells because of, least part, MDM2-mediated ubiquitination proteasomal degradation. When reintroduced into cells, activated p53, caused G1 phase cell cycle...
Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated efficacy with which PL suppresses malignant B derived newly developed, double-transgenic mouse model human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMyc(Eμ). inhibited cell proliferation in concentration-dependent manner and induced apoptosis neoplastic but not cells. Treatment...
The p53 tumor suppressor is controlled by an interactive network of factors that stimulate or inhibit its transcriptional activity. Within network, Mdm2 functions as the major antagonist promoting ubiquitylation and degradation. Conversely, Tip60 activates through direct association on target promoters well acetylation at lysine 120 (K120). This study examines functional relationship between with a novel regulator, NIAM (nuclear interactor ARF Mdm2). Previous work showed can suppress...
Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as gene discovery tool in liver, breast, lung, prostate and other cancers, but been largely neglected studies on neoplasms mature B-lymphocytes such diffuse large B cell lymphoma (DLBCL) Burkitt (BL). We used global profiles DLBCL-like tumors that arose spontaneously Myc-transgenic C57BL/6 mice phylogenetically conserved filter for analyzing human...
Cellular quiescence is a reversible growth arrest in which cells retain their ability to enter into and exit from the proliferative cycle. This study investigates hypothesis that cell growth-state specific oxidative stress response regulates radiosensitivity of cancer cells. Results showed quiescent (low index; >75% G1 phase lower RNA content) Cal27 FaDu human head neck squamous carcinoma (HNSCC) are radioresistant compared proliferating Quiescent exhibited three tenfold increase mRNA levels...
The function of Epstein–Barr virus (EBV) stable intronic sequence (sis)RNAs, non-coding RNAs transcribed from a region required for EBV-mediated cellular transformation, remain unknown. To better understand the ebv-sisRNA-1 and ebv-sisRNA-2 internal repeat (IR)1 EBV, we used combination bioinformatics biochemistry to identify associated RNA binding proteins. findings reported here are part ongoing studies determine functions IR1 EBV. Human regulatory proteins HNRNPA1 (heterogeneous nuclear...
The MYC gene encodes a human transcription factor and proto-oncogene that is dysregulated in over half of all known cancers. To better understand potential post-transcriptional regulatory features affecting expression, we analyzed secondary structures the mRNA using program optimized for finding small locally-folded motifs with high propensity function. This was accomplished by calculating folding metrics across sequence sliding analysis window generating unique consensus base pairing models...
KSHV-encoded vIL-6 collaborates with deregulated c-Myc to drive plasmablastic neoplasms in mice
Abstract Adenovirus E1A oncogene transforms primary rodent fibroblasts in cooperation with activated Ras. Conversely, the c‐Myc oncoprotein‐binding tumor suppressor, Bin1, inhibits Ras/E1A‐mediated cell transformation. Since does not directly bind to and inhibit mechanism by which counteracts Bin1 liberate oncogenic activity is poorly understood. Here we show that wild‐type E1A, but an Rb binding‐defective mutant, suppresses endogenous expression cultured fibroblasts. Similarly, other...
In the present study, we investigated interactions between proteasome inhibitor carfilzomib (CFZ) and histone deacetylase vorinostat in Jurkat T-leukemia cells. Coexposure of cells to minimally lethal concentrations CFZ with very low concentration resulted synergistic antiproliferative effects enhanced apoptosis cells, accompanied sharply increased reactive oxygen species (ROS), striking decrease mitochondrial membrane potential (MMP), release cytochrome c, activation caspase-9 -3, cleavage...
Comparative genetic and biological studies on malignant tumor counterparts in human beings laboratory mice may be powerful gene discovery tools for blood cancers, including neoplasms of mature B-lymphocytes plasma cells such as Burkitt lymphoma (BL) multiple myeloma (MM). We used EMSA to detect constitutive NF-κB/STAT3 activity BL- MM-like that spontaneously developed single-transgenic IL6 (interleukin-6) or MYC (c-Myc) mice, double-transgenic IL6MYC mice. qPCR measurements analysis clinical...
MYC pre-mRNA is spliced with high fidelity to produce the transcription factor known regulate cellular differentiation, proliferation, apoptosis, and alternative splicing. The mechanisms underpinning splicing of , however, remain mostly unexplored. In this study, we examined interaction heterogeneous nuclear ribonucleoprotein C (HNRNPC) intron 2. Building off published eCLIP studies, confirmed poly(U) regions in 2 found that full binding correlated optimal protein production. appears be...