A5042799909- Glioma Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Brain Metastases and Treatment
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- PARP inhibition in cancer therapy
- Circular RNAs in diseases
- Protein Tyrosine Phosphatases
- Melanoma and MAPK Pathways
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Cancer Research and Treatments
- Cell Image Analysis Techniques
- Molecular Biology Techniques and Applications
- Neuroblastoma Research and Treatments
- Nanoplatforms for cancer theranostics
- Pluripotent Stem Cells Research
St. Jude Children's Research Hospital
2019-2024
China Pharmaceutical University
2024
RACK7 recognizes H3.3G34R to suppress expression of MHC II complex components and their delivery pathway in pediatric GBM.
Abstract Background Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating MET receptor tyrosine kinase often occur infant-type hemispheric (IHG) but also other pHGG are associated with devastating morbidity mortality. Methods To identify new treatment options, we established characterized two novel orthotopic mouse models harboring distinct fusions. These included an...
Abstract Pediatric-type diffuse high-grade gliomas are fatal central nervous system malignancies of childhood. Recurrent mutations in histone H3.3 at amino acid 34 (glycine to arginine/valine) a defining molecular feature hemispheric glioma, H3 G34-mutant (H3 DHG), which arises preferentially adolescents and young adults. Single-nuclei sequencing age anatomically matched wild-type primary patient tumors identified aberrant neuronal-like transcriptional programs enriched for signatures...
Abstract Radiation therapy (RT) is currently the standard treatment for diffuse intrinsic pontine glioma (DIPG), most common cause of death in children with brain cancer. A pharmacodynamic model was developed to describe radiation‐induced tumor shrinkage and overall survival mice bearing DIPG. CD1‐nude were implanted cortex luciferase‐labeled patient‐derived orthotopic xenografts DIPG (SJDIPGx7 H3F3A WT / K27 M SJDIPGx37 K27M ). Mice treated image‐guided whole‐brain RT at 1 or 2 Gy/fraction...
Abstract Oncogenic fusion events involving c-MET have been observed in up to 12% of pediatric high-grade glioma (pHGG). MET inhibitors displayed potent initial responses rearranged tumors but acquired resistance single agent modalities invariably occurs. To identify new treatment options against these tumors, we established two novel orthotopic mouse models including an immunocompetent, murine allograft and intracranial patient-derived xenograft (PDX), both harboring distinct fusions. We...
Abstract Pediatric brain tumors comprise a distinct spectrum of diseases compared to adult and are distinguished by their unique clinical histopathological features, developmental context, mutation burden, genomic, epigenomic, transcriptomic alterations. Access in vivo models that recapitulate pediatric has been limited inadequate represent these heterogeneous diseases. Here we introduce the Brain Tumor Portal (PBTP, pbtp.stjude.cloud), an open resource access molecular characterization,...
Abstract Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children. In vitro and vivo disease models reflecting the intimate connection between developmental context pathogenesis of pHGG are essential advance understanding identify therapeutic vulnerabilities. We established 21 patient-derived orthotopic xenograft (PDOX) eight matched cell lines from diverse groups pHGG. These recapitulated histopathology, DNA methylation signatures, mutations gene...
Radiation therapy (RT) is a standard component of postoperative management children with malignant gliomas and the definitive for patients inoperable high-grade glioma (HGG), yet duration benefit generally measured in months to several years. Therefore, it important identify novel systemic agents that enhance therapeutic efficacy care RT. We screened custom library 24 FDA approved drugs late stage clinical candidates reported radiosensitizing activity central nervous system (CNS)...
Abstract Mutations in the gene encoding activin A receptor type 1 (ACVR1) are found approximately 25% of diffuse intrinsic pontine gliomas (DIPGs), a pediatric glioma with 2-year survival rate less than 10%. ACVR1mutations frequently coincide activating PIK3CA or PIK3R1 mutations, indicating potential cooperative effect BMP and PI3K signaling gliomagenesis. We used genetically engineered mice inducible knock-in Acvr1R206H Pik3caE545K alleles, such that cre-mediated recombination resulted...
Abstract High-grade gliomas (HGG) with histone H3.3 G34R mutation are rare intractable tumours in the cerebral hemispheres that preferentially affect adolescents and young adults, but have unknown mechanisms of neuroanatomical specificity tumourigenesis. Here, we performed single-nucleus RNA-sequencing twenty patient samples, encompassing twelve eight wildtype HGGs, age- location-matched. Both classes HGG were heterogeneous, malignant cells multiple states, recapitulating neural glial...