A5089930080- Glioma Diagnosis and Treatment
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Bladder and Urothelial Cancer Treatments
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Hippo pathway signaling and YAP/TAZ
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Neurofibromatosis and Schwannoma Cases
- Urinary and Genital Oncology Studies
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Dementia and Cognitive Impairment Research
- Ubiquitin and proteasome pathways
- Meningioma and schwannoma management
- Prostate Cancer Treatment and Research
Fred Hutch Cancer Center
2014-2024
Universidade de Santiago de Compostela
2023-2024
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2018-2024
Instituto de Investigación Sanitaria de Santiago
2024
Seattle University
2019-2022
Amity University
2022
Kims Bibi Hospital
2022
Cancer Research Center
2018
University of Washington
2018
Icahn School of Medicine at Mount Sinai
2014
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying differences between these two tumor types, immune-related cell content potentially important contributors. In order to investigate role of IDH immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) wtIDH1 gliomas...
Glioblastoma (GBM) is the most aggressive brain tumor in adults. It strongly infiltrated by microglia and peripheral monocytes that support growth. In present study we used RNA sequencing to compare expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) isolated from non-tumor samples. Hierarchical clustering principal component analysis showed a clear separation two sample groups identified 334 significantly regulated genes hGAMs. comparison control hGAMs...
YAP1 is a transcriptional coactivator and the principal effector of Hippo signaling pathway, which causally implicated in human cancer. Several gene fusions have been identified various cancers identifying essential components this family has significant therapeutic value. Here, we show that YAP1-MAMLD1 , YAP1-FAM118B YAP1-TFE3 YAP1-SS18 are oncogenic mice. Using reporter assays, RNA-seq, ChIP-seq, loss-of-function mutations, can all these fusion proteins exert TEAD-dependent YAP activity,...
Abstract The functional consequences of genetic variants within 5’ untranslated regions (UTRs) on a genome-wide scale are poorly understood in disease. Here we develop high-throughput multi-layer genomics method called PLUMAGE (Pooled full-length UTR Multiplex Assay Gene Expression) to quantify the molecular somatic mutations human prostate cancer. We show that can control transcript levels and mRNA translation rates through creation DNA binding elements or RNA-based cis -regulatory motifs....
YAP1 is a transcriptional coactivator regulated by the Hippo signaling pathway, including NF2. Meningiomas are most common primary brain tumors; large percentage exhibit heterozygous loss of chromosome 22 (harboring NF2 gene) and functional inactivation remaining copy, implicating oncogenic YAP activity in these tumors. Recently, fusions between MAML2 have been identified subset pediatric wild-type meningiomas. Here, we show that human YAP1-MAML2 -positive meningiomas resemble mutant global...
Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, few molecular mechanisms critical for CSC population maintenance have been exploited therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators the SOX2-enriched, therapy-resistant niche and identified WDR5 as indispensable this population. is component WRAD complex,...
We uncover a tumor-suppressive process in urothelium called transcriptional-translational conflict caused by deregulation of the central chromatin remodeling component ARID1A. Loss Arid1a triggers an increase nexus pro-proliferation transcripts, but simultaneous inhibition eukaryotic elongation factor 2 (eEF2), which results tumor suppression. Resolution this through enhancing translation speed enables efficient and precise synthesis network poised mRNAs resulting uncontrolled proliferation,...
RNA-sequencing data is widely used to identify disease biomarkers and therapeutic targets using numerical methods such as clustering, classification, regression, differential expression analysis. Such approaches rely on the assumption that mRNA abundance estimates from RNA-seq are reliable of true levels. Here, five processing pipelines applied 6,690 human tumor normal tissues, we show nearly 88% protein-coding genes have similar gene profiles across all pipelines. However, for >12% genes,...
The androgen receptor (AR) regulates mRNA-specific translation through 4EBP1, which is a druggable vulnerability in AR-deficient prostate cancer.
Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, better characterizations their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape 1,298 meningiomas. The clinical genomic metadata effectively correlated with regions, which led identification meningioma subtypes specific...
Abstract Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators erythropoiesis, we utilize a functional genomic screen for genes affecting expression erythroid marker CD235a/GYPA. Among validating hits are coding N 6 -methyladenosine (m A) mRNA methyltransferase (MTase) complex, including, METTL14 , METTL3 WTAP . We demonstrate that m A MTase activity promotes gene programs through selective...
Glioblastoma is the most frequently occurring and invariably fatal primary brain tumor in adults. The vast majority of glioblastomas characterized by chromosomal copy number alterations, including gain whole chromosome 7 loss 10. Gain an early event gliomagenesis that occurs proneural-like precursor cells, which give rise to all isocitrate dehydrogenase (IDH) wild-type glioblastoma transcriptional subtypes. Platelet-derived growth factor A ( PDGFA ) one gene on known drive gliomagenesis,...
Abstract Background Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an “abscopal effect,” whereby unirradiated neoplastic cells outside sites are recognized attacked by the immune system. Radiation combined with anti–programmed cell death ligand 1 (PD-L1) demonstrated modest efficacy in phase II human glioblastoma trials, but mechanism relevance of abscopal effect during this response remain unknown. Methods We...
3′ untranslated region (3′ UTR) somatic mutations represent a largely unexplored avenue of alternative oncogenic gene dysregulation. To determine the significance UTR in disease, we identify variants across 185 advanced prostate tumors, discovering 14,497 single-nucleotide enriched pathways and regulatory elements. By developing two complementary massively parallel reporter assays, measure how thousands patient-based affect mRNA translation stability hundreds functional that allow us to...
Ependymomas (EPN) are central nervous system tumors arising from ependymal cells, primarily affecting young children and accounting for 10% of intracranial in 4% adults. Current treatments limited to surgery radiotherapy, with chemotherapy providing minimal benefit. Over 70% supratentorial ependymomas (ST-EPNs) driven by ZFTA-RELA fusions (ZFTA-RELAfus), which associated poor prognosis. Recent molecular classifications have identified two distinct ST-EPN clusters, E1 E2, the cluster...
Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, death. Glioblastoma stem-like cells (GSCs) are a source tumor formation recurrence glioblastoma multiforme, highly aggressive brain cancer, suggesting that ion channel expression may be perturbed this population. However, little is known about functional relevance contribute to GSC malignancy. Using RNA sequencing, we assessed enrichment isolates...
BACKGROUND. Little is known about the genomic differences between metastatic lower tract urothelial carcinoma (LTUC) and upper (UTUC). We compare features of primary UTUC LTUC tumors in a cohort patients with end-stage disease.
Abstract Independent scientific achievements have led to the discovery of aberrant splicing patterns in oncogenesis, while more recent advances uncovered novel gene fusions involving neurotrophic tyrosine receptor kinases (NTRKs) gliomas. The exploration NTRK splice variants normal and neoplastic brain provides an intersection these two rapidly evolving fields. Tropomyosin kinase B (TrkB), encoded NTRK2 , is known for critical roles neuronal survival, differentiation, molecular properties...
Advanced prostate malignancies are a leading cause of cancer-related deaths in men, large part due to our incomplete understanding cellular drivers disease progression. We investigate cancer cell dynamics at single-cell resolution from onset the development androgen independence an vivo murine model. observe expansion castration-resistant intermediate luminal type that correlates with treatment resistance and poor prognosis human patients. Moreover, transformed epithelial cells associated...