A5006365668- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Neurogenetic and Muscular Disorders Research
- Cancer-related gene regulation
- Sarcoma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
- Chromatin Remodeling and Cancer
- Congenital Anomalies and Fetal Surgery
- MicroRNA in disease regulation
- Pancreatitis Pathology and Treatment
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Renal Diseases and Glomerulopathies
- Protein Degradation and Inhibitors
- TGF-β signaling in diseases
- Neonatal Respiratory Health Research
- Insect Resistance and Genetics
- Lipid metabolism and disorders
- CAR-T cell therapy research
Nationwide Children's Hospital
2015-2025
The Ohio State University
2013-2025
The Ohio State University Wexner Medical Center
2014-2019
Ohio University
2012-2016
The University of Texas MD Anderson Cancer Center
1994-2013
The University of Texas Health Science Center at Houston
2013
Cancer Genetics (United States)
2006
Case Western Reserve University
1994
Loss of the decoy function miR-29 destabilizes A20 transcripts, contributing to oncogenic activation transcription factor NF-κB in sarcomas.
Abstract Rhabdomyosarcoma (RMS) is an aggressive pediatric tumor with a poor prognosis for metastasis and recurrent disease. Large-scale sequencing endeavors demonstrate that Rhabdomyosarcomas have dearth of precisely targetable driver mutations. However, IGF-2 signaling known to be grossly altered in RMS. The insulin receptor (IR) exists two alternatively spliced isoforms, IR-A IR-B. molecule binds both its innate IGF-1 as well the variant A ( ) high affinity. Mitogenic proliferative via...
Abstract The tumor suppressor protein p53 is a transcription factor that induces G1 arrest of the cell cycle and/or apoptosis. murine double-minute MDM2 and its homologue MDM4 (also known as MDMX) are critical regulators p53. Altered transcripts human mdm2, MDM2, have been identified in tumors, such invasive carcinoma breast, lung carcinoma, liposarcoma. alternate forms act to negatively regulate normal gene product, thus activating Although many reports documented plethora types...
X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin. The Mtm1 knockout (KO) mouse has phenotype and its short lifespan (8 weeks) makes it challenge to use as model in testing certain preclinical therapeutics. Many MTM patients succumb early life, but some have more favorable prognosis. We used human genotype–phenotype correlation data develop myotubularin-deficient with...
Abstract Introduction: Dedifferentiated liposarcoma (DDLPS) is a soft tissue sarcoma characterized by genomic amplification of proto-oncogene MDM2 alongside wildtype P53. Disease progression and poor survival rates in DDLPS are driven overexpression, which negatively regulates the tumor suppressor p53. While small molecules such as Nutlin its derivatives have been employed to inhibit MDM2-p53 interaction, their significant toxicity presents major limitation. This clinical challenge...
Abstract Deletion of chromosome 1p35 is a common event in epithelial malignancies. We report that DEAR1 (annotated as TRIM62) tumor suppressor undergoes mutation, copy number variation, and loss expression human tumors. Targeted disruption the mouse recapitulates this spectrum, with both Dear1−/− Dear1+/− mice developing primarily adenocarcinomas lymphoma evidence metastasis subset mice. function presence TGF-β results failure acinar morphogenesis, upregulation epithelial–mesenchymal...
Genotoxic stress induces alternative splicing of the oncogene MDM2 generating MDM2-ALT1, an isoform attributed with tumorigenic properties. However, mechanisms underlying this event remain unclear. Here we explore regulation by utilizing a novel minigene that mimics endogenous in response to UV and cisplatinum-induced DNA damage. We report exon 11 is necessary sufficient for damage-specific factor SRSF1 binds at evolutionarily conserved sites. Interestingly, mutations disrupting interaction...
Background Breast cancer in young women tends to have a natural history of aggressive disease for which rates recurrence are higher than breast cancers detected later life. Little is known about the genetic pathways that underlie early-onset cancer. Here we report discovery DEAR1 (ductal epithelium–associated RING Chromosome 1), novel gene encoding member TRIM (tripartite motif) subfamily finger proteins, and provide evidence its role as dominant regulator acinar morphogenesis mammary gland...
Alternative splicing of the oncogene MDM2 is a phenomenon that occurs in cells response to genotoxic stress and also hallmark several cancer types with important implications carcinogenesis. However, mechanisms regulating this event remain unclear. Previously, we uncovered importance intron 11 affects damage-responsive minigene. Here, have identified discrete cis regulatory elements within report binding FUBP1 (Far Upstream element-Binding Protein 1) these role it plays splicing. Best known...
Proximal spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of the survival motor neuron (SMN) protein. In humans, SMN1 and SMN2 encode SMN SMA patients, gene lost remaining only partially compensates. Mediated C>T nucleotide transition in SMN2, inefficient recognition exon 7 splicing machinery results SMN. Because capable expressing protein, correction an attractive therapeutic option. Although current mouse models characterized Smn knock-out alleles...
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease associated with low levels of the essential survival motor neuron (SMN) protein. Reduced SMN due to loss SMN1 gene and inefficient splicing SMN2 caused by C>T mutation in exon 7. Global analysis severe SMNΔ7 SMA mouse model revealed altered increased hypoxia-inducible transcript, Hif3alpha, at late stages progression. Severe patients also develop respiratory deficiency during We sought evaluate whether hypoxia was...
MDM2 and MDMX are the chief negative regulators of tumor-suppressor protein p53 essential for maintaining homeostasis within cell. In response to genotoxic stress also in several cancer types, alternatively spliced. The splice variants MDM2-ALT1 MDMX-ALT2 lack p53-binding domain incapable negatively regulating p53. However, they retain RING that facilitates dimerization full-length MDM proteins. Concordantly, has been shown lead stabilization through its interaction with inactivation MDM2....
T cells redirected to cancer either via a chimeric antigen receptor (CAR-T) or bispecific molecule have been breakthrough technologies; however, CAR-T require individualized manufacturing and bispecifics generally continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics adeno-associated virus (AAV) gene transfer. demonstrate proof principle in CD19 + lymphoma xenograft model using single intravenous...
Sex determination inDrosophila melanogaster is regulated by a cascade of splicing factors which direct the sex-specific expression gene products needed for male and female differentiation.The factor TRA-2 affects multiple pre-mRNAs involved in sexual tra-2 itself expresses complex set mRNAs generated through alternative processing that collectively encode three distinct protein isoforms.The these isoforms differs soma germ line.In line ratio two present governed autoregulation...
Pediatric rhabdomyosarcoma (RMS) is a morphologically and genetically heterogeneous malignancy commonly classified into three histologic subtypes, namely, alveolar, embryonal, anaplastic. An issue that continues to challenge effective RMS patient prognosis the dearth of molecular markers predictive disease stage irrespective tumor subtype. Our study involving panel 70 tumors has identified specific alternative splice variants oncogenes Murine Double Minute 2 (MDM2) MDM4 as potential...
In the male germline of Drosophila transformer-2 protein is required for differential splicing pre-mRNAs from exuperantia and att genes autoregulates alternative its own pre-mRNA. Autoregulation TRA-2 results in production two mRNAs that differ by splicing/retention M1 intron encode functionally distinct isoforms. Splicing produces an mRNA encoding TRA-2(226), which necessary sufficient both fertility regulation downstream target RNAs. When retained, produced TRA-2(179), a with no known...
MDM2 is an oncogene and critical negative regulator of tumor suppressor p53. Genotoxic stress causes alternative splicing transcripts, which leads to alterations in p53 activity contributes tumorigenesis. MDM2-ALT1 one the alternatively spliced transcripts predominantly produced response genotoxic stress, comprised terminal coding exons 3 12. Previously, we found that SRSF1 induces by promoting exon 11 skipping. Here report SRSF2 antagonizes regulation facilitating inclusion through binding...