A5068461186- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Animal Genetics and Reproduction
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- Nonmelanoma Skin Cancer Studies
- Melanoma and MAPK Pathways
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Bladder and Urothelial Cancer Treatments
Moffitt Cancer Center
2017-2024
Molecular Oncology (United States)
2017-2024
University of South Florida
2018-2022
Houston Methodist
2012-2021
Agency for Science, Technology and Research
2012-2021
Institute of Molecular and Cell Biology
2012-2021
National Cancer Institute
2020-2021
Cancer Genetics (United States)
2020-2021
Center for Cancer Research
2020-2021
Methodist Hospital
2015
Pancreatic cancer is one of the most deadly cancers affecting Western world. Because disease highly metastatic and difficult to diagnosis until late stages, 5-y survival rate around 5%. The identification molecular drivers critical for furthering our understanding development improved diagnostic tools therapeutics. We have conducted a mutagenic screen using Sleeping Beauty ( SB ) in mice identify new candidate genes pancreatic cancer. By combining with an oncogenic Kras allele, we observed...
High spliceosome activity is a dependency for cancer cells, making them more vulnerable to perturbation of the splicing machinery compared normal cells. To identify factors important prostate (PCa) fitness, we performed pooled shRNA screens in vitro and vivo. Our identified heterogeneous nuclear ribonucleoprotein M (HNRNPM) as regulator PCa cell growth. RNA- eCLIP-sequencing HNRNPM binding transcripts key homeostatic genes. its targets prevents aberrant exon inclusion backsplicing events. In...
RNA splicing is an important biological process associated with cancer initiation and progression. However, the contribution of alternative to pancreatic (PDAC) development not well understood. Here, we identify enrichment binding proteins (RBPs) involved in regulation linked PDAC progression from a forward genetic screen using Sleeping Beauty insertional mutagenesis mouse model cancer. We demonstrate downregulation RBFOX2, RBP FOX family, promotes liver metastasis. Specifically, show RBFOX2...
Abstract Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment patients FDA-approved inhibitors BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression the epithelium initiates growth benign tumors that, without additional genetic alterations, rarely progress to malignant adenocarcinoma. To identify genes that cooperate progression, we used Sleeping...
Large-scale oncogenomic studies have identified few frequently mutated cancer drivers and hundreds of infrequently drivers. Defining the biological context for rare driving events is fundamentally important to increasing our understanding druggable pathways in cancer. Sleeping Beauty (SB) insertional mutagenesis a powerful gene discovery tool used model human cancers mice. Our lab others published number that identify from these models using various statistical computational approaches....
The p53 transcription factor modulates gene expression programs that induce cell cycle arrest, senescence, or apoptosis, thereby preventing tumorigenesis. However, the mechanisms by which these fates are selected unclear. Our objective is to understand target selection and, thus, enable its optimal manipulation for cancer therapy. We have generated targeted transgenic reporter mice in EGFP driven transcriptional activity at a response element from either p21 Puma promoter, induces...
The tumour suppressor p53 is regulated primarily at the protein level. In normal tissues its levels are maintained a very low level by action of specific E3 ligases and ubiquitin proteosome pathway. mutant contributes to transformation, metastasis drug resistance. High can be found in tumours accumulation has previously been reported pathologically cells human skin. We show for first time that similarly elevated detected apparently knock-in mouse model. fact, small intestine, spontaneously...
Cancer driver prioritization for functional analysis of potential actionable therapeutic targets is a significant challenge. Meta-analyses mutated genes across different human cancer types has reaffirmed the role major players in cancer, including KRAS, TP53 and EGFR, but had limited success prioritizing with non-recurrent mutations specific types. Sleeping Beauty (SB) insertional mutagenesis powerful experimental gene discovery framework to define mouse models cancers. SB datasets multiple...
Transposon-based insertional mutagenesis in the mouse provides a powerful approach for identifying new cancer genes. Transposon insertions genes are selected during tumor development because of their positive effect on growth, and transposon insertion sites tumors thus serve as tags Direct comparisons transposon-mutated with mutated human can lend insight into signaling pathways that drive tumorigenesis. This is critical prioritizing further study, either efficacy biomarkers or drug targets....
The systematic identification of genetic events driving cellular transformation and tumor progression in the absence a highly recurrent oncogenic driver mutation is challenge cutaneous oncology. In squamous cell carcinoma (cuSCC), high UV-induced mutational burden poses hurdle to achieve complete molecular landscape this disease. Here, we utilized Sleeping Beauty transposon mutagenesis system statistically define drivers keratinocyte cuSCC vivo UV-IR, identified both known suppressor genes...
Abstract The systematic identification of genetic events driving cellular transformation and tumor progression in the absence a highly recurrent oncogenic driver mutation is challenge cutaneous oncology. In squamous cell carcinoma (cuSCC), high UV-induced mutational burden poses hurdle to achieve complete molecular landscape this disease. Here, we utilized Sleeping Beauty transposon mutagenesis system statistically define drivers keratinocyte cuSCC vivo UV-IR, identified both known...
<h3>Background</h3> Overall, 30% of human cancers are driven by mutant RAS proteins, which have historically been difficult to target. While immunotherapy is effective for <i>NRAS</i>-mutant melanoma, resistant disease inadequately addressed, and <i>KRAS</i>-driven carcinomas much less responsive. Oncogenic pathways often key targets inhibition. Even so, resistance the inability safely combine these approaches with immunotherapies remain major challenges. The idea oncogenic pathway agonism...
A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor gene mutations driving cellular transformation progression absence oncogenic driver mutation(s). Multiple vitro vivo inactivation screens have enhanced our understanding landscape various cancers. However, these studies are limited to or combination effects, specific organs, require sensitizing mutations. In this study, we developed utilized a Sleeping Beauty transposon...
Abstract A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor genes driving cellular transformation progression absence oncogenic driver mutation(s). Multiple vitro vivo gene inactivation screens have enhanced our understanding landscape various cancers. However, these studies are limited to or combination effects, specific organs, require sensitizing mutations. In this study, we developed utilized a Sleeping Beauty transposon...
Abstract Bladder cancer is the 9 th most commonly diagnosed cancer. Nearly half of patients with early stage bladder treated immune-stimulating agent BCG have disease recurrence, while 13% progress to invasive Here we explored potential tumor mutational heterogeneity and role pro- anti-inflammatory cytokines identify different subtypes that may predict therapeutic response BCG. Further, used mathematical modeling dosing strategies infer varying doses time schedules f administration. As a...
Abstract Myeloid leukemia is associated with few predominant mutations and translocations in humans. In order to uncover additional loci that drive the disease, we developed an aggressive, fully-penetrant mouse model of myeloid using Sleeping Beauty insertional mutagenesis. Animals distinct foci expanded splenic red pulp as early 30 days age had a median survival 70 days. SB insertions sequenced from 168 spleens mice end-stage disease revealed more than 470 statistically defined candidate...
Abstract Protein posttranslational modification (PTM) plays a pivotal role in cancer progression through regulating gene expression, protein activities and stabilization. These chemistry events are regarded as potential biomarkers for diagnosis, prognosis, therapeutic efficacy evaluation. Hydroxylated proline is the most common PTM amino acid residue proteome. However, this often overlooked. Here, we demonstrate expression level of prolyl-4-hydroxylase alpha-1(P4HA1) tumor tissues ratio its...