Charles G. Eberhart
A5019028542- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Ocular Oncology and Treatments
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Cancer Mechanisms and Therapy
- Cancer-related molecular mechanisms research
- Neuroblastoma Research and Treatments
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Circular RNAs in diseases
- interferon and immune responses
- Corneal Surgery and Treatments
- Protein Degradation and Inhibitors
- Corneal surgery and disorders
- Cancer-related Molecular Pathways
- Glaucoma and retinal disorders
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Developmental Biology and Gene Regulation
- Hippo pathway signaling and YAP/TAZ
- Microtubule and mitosis dynamics
- Neurofibromatosis and Schwannoma Cases
Johns Hopkins Medicine
2016-2025
Johns Hopkins University
2016-2025
Sidney Kimmel Comprehensive Cancer Center
2015-2024
University of Baltimore
2013-2024
Johns Hopkins Hospital
2015-2024
National Institute of Neurological Disorders and Stroke
2024
Heidelberg University
2010-2023
Smith-Kettlewell Eye Research Institute
2023
Kennedy Krieger Institute
2014-2023
University of Michigan–Ann Arbor
2011-2022
Medulloblastoma, a small blue cell malignancy of the cerebellum, is major cause morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication stratification include factors (age, presence metastases, extent resection) as well histological subgrouping (classic, desmoplastic, large cell/anaplastic histology). Transcriptional profiling studies medulloblastoma cohorts from several research groups around globe have suggested existence multiple distinct molecular...
Recent genomic approaches have suggested the existence of multiple distinct subtypes medulloblastoma. We studied a large cohort medulloblastomas to determine how many subgroups disease exist, they differ, and extent overlap between subgroups.We determined gene expression profiles DNA copy number aberrations for 103 primary medulloblastomas. Bioinformatic tools were used class discovery medulloblastoma based on most informative genes in data set. Immunohistochemistry subgroup-specific...
The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres other genomic sites. Because inactivating mutations of these genes are common human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status tumors. We found that 61% PanNETs displayed abnormal characteristic a telomerase-independent maintenance mechanism termed ALT (alternative lengthening telomeres). All exhibiting had or loss nuclear protein. also correlate with central nervous...
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique...
Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth established tumors unclear. Here, we investigate therapeutic efficacy Hh antagonist cyclopamine preclinical models medulloblastoma, most common malignant brain tumor children. Cyclopamine treatment murine medulloblastoma cells blocked proliferation vitro and induced changes gene expression consistent neuronal differentiation loss stem cell–like character. This compound...
Medulloblastomas are heterogeneous tumors that collectively represent the most common malignant brain tumor in children. To understand molecular characteristics underlying their heterogeneity and to identify whether such risk factors for patients with this disease, we performed an integrated genomic analysis of a large series primary tumors.We profiled mRNA transcriptome 194 medulloblastomas high-density single nucleotide polymorphism array miRNA on 115 98 these, respectively. Non-negative...
Cancer stem cells (CSCs) are thought to be critical for the engraftment and long-term growth of many tumors, including glioblastoma (GBM). The at least partially spared by traditional chemotherapies radiation therapies, finding new treatments that can target CSCs may improving patient survival. It has been shown NOTCH signaling pathway regulates normal in brain, GBMs contain stem-like with higher activity. We therefore used low-passage established GBM-derived neurosphere cultures examine...
Abstract The Notch signaling pathway is required in both nonneoplastic neural stem cells and embryonal brain tumors, such as medulloblastoma, which are derived from cells. We investigated the effects of inhibition on medulloblastoma growth using pharmacologic inhibitors γ-secretase. blockade suppressed expression target Hes1 caused cell cycle exit, apoptosis, differentiation lines. Interestingly, viable populations better-differentiated continued to grow when activation was inhibited but...
Nanoparticles densely coated with poly(ethylene glycol) rapidly penetrate within mouse, rat, and human brain parenchyma.
Abstract Brain tumors can arise following deregulation of signaling pathways normally activated during brain development and may derive from neural stem cells. Given the requirement for Hedgehog in non-neoplastic cells, we investigated whether blockade could target stem-like population glioblastoma multiforme (GBM). We found that Gli1, a key pathway target, was highly expressed 5 19 primary GBM 4 7 cell lines. Shh ligand some tumors, GBM-derived neurospheres, suggesting potential mechanism...
The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 its ligands, Delta-like-1 Jagged-1, are overexpressed many glioma lines primary human gliomas. Immunohistochemistry a tissue array shows the presence nucleus intracellular domain, indicating activation situ. Down-regulation Notch-1, Delta-like-1, or Jagged-1 by RNA interference induces apoptosis inhibits proliferation multiple lines. In...
Major discoveries in the biology of nervous system tumors have raised question how non-histological data such as molecular information can be incorporated into next World Health Organization (WHO) classification central tumors. To address this question, a meeting neuropathologists with expertise diagnosis was held Haarlem, Netherlands, under sponsorship International Society Neuropathology (ISN). Prior to meeting, participants solicited input from clinical colleagues diverse...
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...
Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through inclusion molecular subgroup profiles.We determined affiliation, mutation status, and clinical outcome a discovery cohort 397 medulloblastomas. subsequently validated our results on an independent 156 medulloblastomas.TP53 are enriched wingless (WNT; 16%) sonic hedgehog (SHH; 21%) medulloblastomas virtually absent subgroups 3 4 tumors (P < .001). Patients...
Abstract The role of Notch signaling in tumorigenesis can vary; Notch1 acts as an oncogene some neoplasms, and a tumor suppressor others. Here, we show that different receptors have opposite effects single type. Expression truncated, constitutively active or Notch2 embryonal brain cell lines caused antagonistic on growth. Cell proliferation, soft agar colony formation, xenograft growth were all promoted by inhibited Notch1. We also found receptor transcripts are highly expressed progenitor...
The diagnosis of medulloblastoma likely encompasses several distinct entities, with recent evidence for the existence at least four unique molecular subgroups that exhibit genetic, transcriptional, demographic, and clinical features. Assignment subgroup through routine profiling high-quality RNA on expression microarrays is impractical in setting. planning execution trials stratify by subgroup, or which are targeted to a specific requires technologies can be economically, rapidly, reliably,...