Jo Lynne Rokita
A5003443322- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- Hippo pathway signaling and YAP/TAZ
- ATP Synthase and ATPases Research
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Industrial Vision Systems and Defect Detection
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Molecular Biology Techniques and Applications
- Historical, Religious, and Philosophical Studies
- Folklore, Mythology, and Literature Studies
- Linguistics and language evolution
- Epigenetics and DNA Methylation
- Handwritten Text Recognition Techniques
- CAR-T cell therapy research
- Cancer therapeutics and mechanisms
- Genomics and Rare Diseases
- Virus-based gene therapy research
- Medical Imaging Techniques and Applications
- Ferroptosis and cancer prognosis
Children's Hospital of Philadelphia
2019-2025
Children's National
2025
University of Pennsylvania
2019-2025
George Washington University
2025
University of California, San Francisco
2025
Alex's Lemonade Stand Foundation
2021-2022
Philadelphia University
2021
Shriners Hospitals for Children - Philadelphia
2019
Sidney Kimmel Cancer Center
2019
We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA and proteomics phosphoproteomics profiling, of 218 tumors across 7 histological types childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span boundaries, suggesting treatments used for one type may be applied...
Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving diagnosis relapsed disease, limited therapeutic options. To systematically prioritize rationally test novel agents in preclinical murine models, researchers the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)—many which refractory to current...
Abstract Neuroblastoma is a childhood cancer with heterogeneous clinical outcomes. To comprehensively assess the impact of telomere maintenance mechanism (TMM) on outcomes in high-risk neuroblastoma, we integrated C-circle assay [a marker for alternative lengthening telomeres (ALT)], TERT mRNA expression by RNA-sequencing, whole-genome/exome sequencing, and covariates 134 neuroblastoma patient samples at diagnosis. In addition, assessed TMM cell lines (n = 104) patient-derived xenografts...
Pediatric brain tumors are the leading cause of cancer-related death in children United States and contribute a disproportionate number potential years life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary The Children's Brain Tumor Network (CBTN) is multi-institutional international clinical research consortium created advance therapeutic development through collection rapid distribution biospecimens data via open-science...
PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, Children's Brain Tumor Network (CBTN) Pacific Neuro-Oncology Consortium (PNOC) created a systematic process tumor biobanking, model generation, sequencing with immediate access to harmonized data. We leverage data establish OpenPBTA, an open collaborative project over 40 scalable...
Abstract Background Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited. Methods We performed genetic ancestry prediction 1,452 pediatric patients with paired normal tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project evaluate influence of reported race ethnicity ancestry-based superpopulations on histology, molecular subtype, survival,...
A heritable polymorphism within regulatory sequences of the LMO1 gene is associated with its elevated expression and increased susceptibility to develop neuroblastoma, but oncogenic pathways downstream transcriptional co-regulatory protein are unknown. Our ChIP-seq RNA-seq analyses reveal that a key directly regulated by MYCN ASCL1, which encodes basic helix-loop-helix transcription factor. Regulatory elements controlling ASCL1 bound LMO1, factors GATA3, HAND2, PHOX2B, TBX2 ISL1-all members...
Abstract Understanding the aberrant transcriptional landscape of neuroblastoma is necessary to provide insight underlying influences initiation, progression and persistence this developmental cancer. Here, we present chromatin immunoprecipitation sequencing (ChIP-Seq) data for oncogenic transcription factors, MYCN MYC, as well regulatory histone marks H3K4me1, H3K4me3, H3K27Ac, H3K27me3 in ten commonly used human neuroblastoma-derived cell line models. In addition, all profiled lines...
Abstract Relapsed neuroblastomas are enriched with activating mutations of the RAS–MAPK signaling pathway. The MEK1/2 inhibitor trametinib delays tumor growth but does not sustain regression in neuroblastoma preclinical models. Recent studies have implicated Hippo pathway transcriptional coactivator protein YAP1 as an additional driver relapsed neuroblastomas, well a mediator resistance other cancers. Here, we used highly annotated set high-risk cellular models to modulate expression and RAS...
<h3>Background</h3> Unlike some adult cancers, most pediatric cancers are considered immunologically cold and generally less responsive to immunotherapy. While immunotherapy has already been incorporated into standard of care treatment for patients with high-risk neuroblastoma, overall survival remains poor. In a mouse melanoma model, we found that radiation tumor-specific immunocytokine generate an in situ vaccination response syngeneic mice bearing large tumors. Here, tested whether novel...
Pediatric brain tumors are the leading cause of cancer death in children with an urgent need for innovative therapies. Glypican 2 (GPC2) is a cell surface oncoprotein expressed neuroblastoma which targeted immunotherapies have been developed. This work aimed to characterize GPC2 expression pediatric and develop mRNA CAR T approach against this target.We investigated across cohort primary tumor samples lines using RNA sequencing, immunohistochemistry, flow cytometry. To target adoptive...
Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, ontology. Transcriptomic analyses human medulloblastoma, the most common malignant pediatric brain cancer, showed medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated by single-cell RNA sequencing autochthonous murine SHH-MB at steady state under two...
Abstract Background High-risk neuroblastoma is a complex genetic disease that lethal in more than 50% of patients despite intense multimodal therapy. Through genome-wide association studies (GWAS) and next-generation sequencing, we have identified common single nucleotide polymorphisms rare, pathogenic or likely germline loss-of-function variants BARD1 enriched patients. The functional implications these findings remain poorly understood. Methods We correlated genotype with expression normal...
Abstract Summary With the increasing rates of exome and whole genome sequencing, ability to classify large sets germline sequencing variants using up-to-date American College Medical Genetics—Association for Molecular Pathology (ACMG-AMP) criteria is crucial. Here, we present Automated Germline Variant Pathogenicity (AutoGVP), a tool that integrates variant pathogenicity annotations from ClinVar sequence classifications modified version InterVar (PVS1 strength adjustments, removal PP5/BP6)....
The PNOC001 phase II single-arm trial sought to estimate progression-free survival (PFS) associated with everolimus therapy for progressive/recurrent pediatric low-grade glioma (pLGG) on the basis of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) pathway activation as measured by phosphorylated-ribosomal protein S6 and identify prognostic predictive biomarkers.
Abstract To overcome the paucity of known tumor-specific surface antigens in pediatric high-grade glioma (pHGG), we contrasted splicing patterns pHGGs and normal brain samples. Among alternative events affecting extracellular protein domains, most pervasive alteration was skipping ≤30 nucleotide-long microexons. Several these skipped microexons mapped to L1-IgCAM family members, such as NRCAM . Bulk single-nuclei short- long-read RNA-seq revealed uniform 5 19 virtually every pHGG sample....
Abstract Mutations in the tyrosine kinase domain of Anaplastic Lymphoma Kinase (ALK) oncogene neuroblastoma occur most frequently at one three hotspot amino acid residues, with F1174* and F1245* variants conferring de novo resistance to first second generation ALK inhibitors including crizotinib ceritinib. Lorlatinib, a third ALK/ROS inhibitor, overcomes induces complete sustained tumor regressions patient-derived xenograft (PDX) models unresponsive crizotinib. Lorlatinib has now completed...
Abstract The contribution of rare pathogenic/likely pathogenic (P/LP) germline variants to pediatric central nervous system (CNS) tumor development remains understudied. Here, we characterized the prevalence and clinical significance P/LP in cancer predisposition genes across 830 CNS patients from Pediatric Brain Tumor Atlas (PBTA). We identified 24.2% (201/830) majority (154/201) lacked reporting genetic syndromes. Among carriers, 30.7% had putative somatic second hits or loss function...
<h3>ABSTRACT</h3> <h3>BACKGROUND AND PURPOSE:</h3> Cancers show heterogeneity at various levels, from genome to radiological imaging. This study aimed explore the interplay between genomic, transcriptomic, and radiophenotypic data in pediatric low-grade glioma (pLGG), most common group of brain tumors children. <h3>MATERIALS METHODS:</h3> We analyzed 201 pLGG patients Children's Brain Tumor Network (CBTN), using principal component analysis K-Means clustering on 881 radiomic features, along...
Abstract Purpose: DROSHA, DGCR8, and DICER1 regulate microRNA biogenesis are commonly mutated in cancer. Whereas DGCR8 germline pathogenic variants (GPVs) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs clinical phenotypes has been reported. Experimental Design: After obtaining informed consent, sequencing was performed on samples from all patients. The occurrence of investigated large pediatric adult cancer datasets. population prevalence the UK Biobank...