Brent A. Orr
A5031000945- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Genomics and Rare Diseases
- Cancer, Hypoxia, and Metabolism
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Meningioma and schwannoma management
- Ocular Oncology and Treatments
- Sarcoma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Neurofibromatosis and Schwannoma Cases
- Protein Degradation and Inhibitors
- Single-cell and spatial transcriptomics
- Hippo pathway signaling and YAP/TAZ
- Brain Metastases and Treatment
- Genetic factors in colorectal cancer
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Cancer Cells and Metastasis
St. Jude Children's Research Hospital
2016-2025
Cleveland Clinic
2024
Children's Research Hospital
2022-2024
Johns Hopkins Hospital
2011-2017
University of Tennessee Health Science Center
2014-2017
Sidney Kimmel Comprehensive Cancer Center
2017
Bloomberg (United States)
2017
Semmes Murphey Foundation
2014-2017
Le Bonheur Children's Hospital
2017
Louisiana State University Health Sciences Center New Orleans
2017
cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches CNS Tumor Taxonomy) was established evaluate make practical recommendations on recent advances in the field of tumor classification, particularly light rapid progress molecular insights into these neoplasms. For Round 2 its deliberations, Working Committee 3 reconstituted convened Utrecht, The Netherlands, for a meeting designed review putative new types advance any future World Health Organization classification. In...
Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB).
Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities tumor cells to proliferate and spread anatomically, the presence clonal advantageous genetic changes. However, universal highly specific markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in cancers. We show that nearly half all cancers immunoreactive for LINE-1-encoded protein. LINE-1 protein is common feature many types...
Abstract Effective data sharing is key to accelerating research improve diagnostic precision, treatment efficacy, and long-term survival in pediatric cancer other childhood catastrophic diseases. We present St. Jude Cloud (https://www.stjude.cloud), a cloud-based data-sharing ecosystem for accessing, analyzing, visualizing genomic from >10,000 patients with survivors, >800 sickle cell patients. Harmonized totaling 1.25 petabytes are freely available, including 12,104 whole...
SJMB03 (ClinicalTrials.gov identifier: NCT00085202) was a phase III risk-adapted trial that aimed to determine the frequency and clinical significance of biological variants genetic alterations in medulloblastoma.
Standard therapies for high grade glioma have failed to substantially improve survival and are associated with significant morbidity. At relapse, gliomas, such as glioblastoma multiforme, refractory therapy universally fatal. BRAF V600E-mutations been described in a modest 6% 7% of primary central nervous system (CNS) tumors, but increased prevalence the pediatric population certain brain tumor subtypes. The use inhibitors transformed melanoma however their tumors remains unproven. We...
Epigenetic modification of DNA by cytosine methylation to produce 5-methylcytosine (5mC) has become well-recognized as an important epigenetic process in human health and disease. Recently, further 5mC the ten eleven translocated (TET) family enzymes 5-hydroxymethylcytosine (5hmC) been described. In present study, we used immunohistochemistry evaluate distribution 5hmC brain during different periods development a large series gliomas (n = 225). We found that development, levels are high more...
The hippo pathway and its downstream mediator yes-associated protein 1 (YAP1) regulate mammalian organ size in part through modulating progenitor cell numbers. YAP1 has also been implicated as an oncogene multiple human cancers. Currently, little is known about the expression of either normal brain tissue or central nervous system neoplasms. We used immunohistochemistry to evaluate nuclear fetal adult brains 264 tumors. was expressed regions harbor neural cells, but there immunoreactivity...
The stromal microenvironment has key roles in prostate development and cancer, cancer-associated fibroblasts (CAFs) stimulate tumourigenesis via several mechanisms including the expression of pro-tumourigenic factors. Mesenchyme (embryonic stroma) controls organogenesis, some circumstances can re-differentiate tumours. We have applied next-generation Tag profiling to fetal human prostate, normal (NPFs) CAFs identify molecules expressed prostatic stroma. Comparison gene profiles a...
The permanent defects in bone growth observed preclinical studies of hedgehog (Hh) pathway inhibitors were not substantiated early phase clinical vismodegib children. Consequently, advanced into pediatric trials for malignancies suspected being driven by aberrant activation the Hh pathway. In one multicenter II trial, was added to therapy regimen newly diagnosed activated medulloblastoma. Herein, we report on 3 children (2 trial and off trial) treated with who developed widespread plate...
Genomic studies of pediatric cancer have primarily focused on specific tumor types or high-risk disease. Here, we used a three-platform sequencing approach, including whole-genome (WGS), whole-exome (WES), and RNA (RNA-seq), to examine germline genomes from 309 prospectively identified children with newly diagnosed (85%) relapsed/refractory (15%) cancers, unselected for type. Eighty-six percent patients harbored diagnostic (53%), prognostic (57%), therapeutically relevant (25%), and/or...
Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation RB1 gene. Children germline mutations in have high likelihood retinoblastoma and other malignancies later life. Genetically engineered mouse models share some similarities human but there are differences their cellular differentiation. To develop laboratory model formation, we make induced pluripotent stem cells (iPSCs) from 15 participants mutations. Each cell lines validated,...
We sought to investigate clinical outcomes of relapsed medulloblastoma and compare molecular features between patient-matched diagnostic tumors.Children infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced relapse were analyzed for outcomes, including anatomic temporal patterns postrelapse survival. A largely independent, paired cohort was by DNA methylation array next-generation sequencing.A total 72 329 (22%) 52 79 (66%) patients with significant...