A5026287954- Neuroblastoma Research and Treatments
- Virus-based gene therapy research
- Neuroendocrine Tumor Research Advances
- Single-cell and spatial transcriptomics
- Respiratory viral infections research
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Neonatal Respiratory Health Research
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Influenza Virus Research Studies
- Lung Cancer Research Studies
St. Jude Children's Research Hospital
2021-2024
Degradation of RBM39 by indisulam leads to exceptional response in high-risk neuroblastoma.
Abstract Background Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need better understanding of the relationship between patient tumor heterogeneity and models. Results Here, generate single-cell RNA-seq maps neuroblastoma cell lines, patient-derived xenograft models (PDX), genetically engineered mouse model (GEMM). We...
<div>Abstract<p>c-MYC is an important driver of high-risk neuroblastoma. A lack c-MYC–driven genetically engineered mouse models (GEMM) has hampered the ability to better understand mechanisms neuroblastoma oncogenesis and develop effective therapies. In this study, we showed that conditional c-MYC induction via Cre recombinase driven by a tyrosine hydroxylase promoter led preponderance <i>PDX1</i><sup>+</sup> somatostatinoma, type pancreatic...
<p>Supplementary Data including 12 figures and table S1</p>
Abstract The MYC proto-oncogenes (c-MYC, MYCN , MYCL ) are among the most deregulated oncogenic drivers in human malignancies including high-risk neuroblastoma, 50% of which -amplified. Genetically engineered mouse models (GEMMs) based on transgene have greatly expanded understanding neuroblastoma biology and powerful tools for testing new therapies. However, a lack c-MYC–driven GEMMs has hampered ability to better understand mechanisms oncogenesis therapy development given that c-MYC is...
Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need better understanding of the relationship between patient tumor heterogeneity and models. Here, generated single-cell RNA-seq maps neuroblastoma cell lines, patient-derived xenograft models (PDX), genetically engineered mouse model (GEMM). We developed an unsupervised machine...
Abstract High-risk neuroblastoma is one of the most difficult to treat pediatric cancers, with a survival rate only about 50% and significant long-term consequences from current chemotherapy. Preclinical models such as cell lines mice are backbone drug development experimental-mechanistic oncology, but new treatments hampered in part by lack understanding direct clinical relevance data collected preclinical models. Despite this, few formal methods have been developed determine how these...
The cellular plasticity of neuroblastoma is defined by a mixture two major cell states, adrenergic (ADRN) and mesenchymal (MES), which may contribute to therapy resistance. However, how cells switch states during remains largely unknown eradicate regardless their clinical challenge. To better understand the lineage in chemoresistance, we comprehensively transcriptomic epigenetic map ADRN MES types neuroblastomas using human murine models treated with indisulam, selective RBM39 degrader. We...
Abstract Preclinical models such as cell lines and mice are the backbone of drug development experimental-mechanistic oncology. However, we currently lack a detailed understanding direct clinical relevance data collected in most preclinical models, hampering new treatments. Despite this, few formal approaches have been proposed to determine how various represent/resemble primary patient tumors. Here, present first comprehensive single-cell RNA-seq analysis neuroblastoma across an extensive...
Abstract c-MYC is an important driver of high-risk neuroblastoma. A lack c-MYC–driven genetically engineered mouse models (GEMM) has hampered the ability to better understand mechanisms neuroblastoma oncogenesis and develop effective therapies. Here, we showed that conditional induction via Cre recombinase driven by a tyrosine hydroxylase (Th) promoter led preponderance PDX1+ somatostatinoma, type pancreatic neuroendocrine tumor (PNET). However, activation improved dopamine β-hydroxylase...
Abstract Pregnant women and infants are considered high-risk groups for increased influenza disease severity. While virus vaccines recommended during pregnancy, cannot be vaccinated until at least six months of age. Passive transfer maternal antibodies (matAbs) becomes vital the infant’s protection. Here, we employed an ultrasound-based timed-pregnancy murine model examined matAb responses to distinct vaccine platforms A (IAV) infection in dams their offspring. We demonstrate vaccinating...