A5033683673- Glioma Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Meningioma and schwannoma management
- Neuroblastoma Research and Treatments
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
- MicroRNA in disease regulation
- Brain Metastases and Treatment
- Chromatin Remodeling and Cancer
- RNA Research and Splicing
- Ocular Oncology and Treatments
- Single-cell and spatial transcriptomics
- Pituitary Gland Disorders and Treatments
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Hippo pathway signaling and YAP/TAZ
- Microtubule and mitosis dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- CAR-T cell therapy research
- Mitochondrial Function and Pathology
- Mathematical Biology Tumor Growth
- Alzheimer's disease research and treatments
National Cancer Institute
2023-2025
Center for Cancer Research
2023-2025
National Institute of Neurological Disorders and Stroke
2022-2024
National Institutes of Health
2022-2024
Government of the United States of America
2024
Johns Hopkins Medicine
2024
Johns Hopkins University
2024
Office of Extramural Research
2024
University of Washington
2013-2023
University of Michigan
2023
Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, their relationships to histologic features routinely used for diagnosis unclear. We present the Ivy Atlas, anatomically based transcriptional atlas of human glioblastoma aligns individual with genomic alterations gene expression patterns, thus assigning information most important morphologic hallmarks tumor. its clinical database freely accessible online data...
Treatment of the tumor and dural margin with surgery sometimes radiation are cornerstones therapy for meningioma. Molecular classifications have provided insights into biology disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular 1,686 tumors 100 prospective from RTOG-0539 phase 2 trial define biomarkers response. Using propensity score matching, found that gross resection was associated longer...
We performed proteomic analysis of neurofibrillary tangles (NFTs) obtained by laser capture microdissection from pyramidal neurons in hippocampal sector CA1 patients with Alzheimer disease (AD) using liquid chromatography (LC)-mass spectrometry (MS)/MS. discovered a total 155 proteins captured NFT's, 72 which were identified multiple unique peptides. Of these proteins, 63 had previously unknown association NFTs; one was glyceraldehyde-3-phosphate dehydrogenase (GAPDH). validated...
Recent updating of the World Health Organization (WHO) classification central nervous system (CNS) tumors in 2016 demonstrates first organized effort to restructure brain tumor by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS diagnostic criteria also attempt reduce interobserver variability histological interpretation and provide more accurate stratification related clinical outcome. As an example, diffuse gliomas (WHO grades II–IV) are now...
Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding pathogenetic mechanisms and patient stratification. Concurrently, role immune cells microenvironment has received increasing attention, especially T tumor-associated macrophages (TAM). The latter are mixed population activated brain-resident microglia infiltrating...
YAP1 is a transcriptional coactivator and the principal effector of Hippo signaling pathway, which causally implicated in human cancer. Several gene fusions have been identified various cancers identifying essential components this family has significant therapeutic value. Here, we show that YAP1-MAMLD1 , YAP1-FAM118B YAP1-TFE3 YAP1-SS18 are oncogenic mice. Using reporter assays, RNA-seq, ChIP-seq, loss-of-function mutations, can all these fusion proteins exert TEAD-dependent YAP activity,...
YAP1 is a transcriptional coactivator regulated by the Hippo signaling pathway, including NF2. Meningiomas are most common primary brain tumors; large percentage exhibit heterozygous loss of chromosome 22 (harboring NF2 gene) and functional inactivation remaining copy, implicating oncogenic YAP activity in these tumors. Recently, fusions between MAML2 have been identified subset pediatric wild-type meningiomas. Here, we show that human YAP1-MAML2 -positive meningiomas resemble mutant global...
Abstract Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves structures, and displays loss p.K28me3 (K27me3) expression by immunohistochemistry characteristic genetic/epigenetic profile. Rare examples a glioma with p.K28M (K27M) mutation without involvement the so-called “diffuse hemispheric mutation” (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases radiologically...
Children with neurofibromatosis type 1 (NF1) develop optic pathway gliomas, which result from impaired NF1 protein regulation of Ras activity. One obstacle to the implementation biologically targeted therapies is an incomplete understanding individual contributions downstream effectors (mitogen-activated kinase [MEK], Akt) glioma maintenance. This study was designed address importance MEK and Akt signaling Nf1 growth. Primary neonatal mouse astrocyte cultures were employed determine...
Solid cancers develop within a supportive microenvironment that promotes tumor formation and growth through the elaboration of mitogens chemokines. Within these tumors, monocytes (macrophages microglia) represent rich sources stromal factors. Leveraging genetically engineered mouse model neurofibromatosis type 1 (NF1) low-grade brain (optic glioma), we have previously demonstrated microglia are essential for glioma maintenance. To identify potential tumor-associated microglial factors...
Abstract Paediatric high-grade gliomas (HGGs) account for the most brain tumour-related deaths in children and have a median survival of 12–15 months. One promising avenue research is development novel therapies targeting properties non-neoplastic cell-types within tumour such as associated macrophages (TAMs). TAMs are immunosuppressive promote malignancy adult HGG; however, paediatric medulloblastoma, exhibit anti-tumour properties. Much known about HGG, yet little them setting. This raises...
Mutations of the isocitrate dehydrogenase (IDH) gene are common genetic mutations in human malignancies. Increasing evidence indicates that IDH play critical roles malignant transformation and progression. However, therapeutic options for IDH-mutated cancers remain limited. In this study, investigation patient cohorts revealed PI3K/protein kinase B (AKT) signaling pathways were enhanced cancer cells.In we investigated expression profile cells using RNA sequencing after depletion AKT. Gene...
Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, better characterizations their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape 1,298 meningiomas. The clinical genomic metadata effectively correlated with regions, which led identification meningioma subtypes specific...
Abstract High‐grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter‐ intra‐tumoral heterogeneity. The key histological hallmarks of glioblastoma pseudopalisading necrosis microvascular proliferation, which allow pathologists distinguish from lower‐grade gliomas. In addition being genetically molecularly heterogeneous, HGG also heterogeneous with respect the composition their microenvironment. question whether this...
Glioblastoma is the most frequently occurring and invariably fatal primary brain tumor in adults. The vast majority of glioblastomas characterized by chromosomal copy number alterations, including gain whole chromosome 7 loss 10. Gain an early event gliomagenesis that occurs proneural-like precursor cells, which give rise to all isocitrate dehydrogenase (IDH) wild-type glioblastoma transcriptional subtypes. Platelet-derived growth factor A ( PDGFA ) one gene on known drive gliomagenesis,...
Abstract Intraoperative consultations, used to guide tumor resection, can present histopathological findings that are challenging interpret due artefacts from tissue cryosectioning and conventional staining. Stimulated Raman histology (SRH), a label-free imaging technique for unprocessed biospecimens, has demonstrated promise in limited subset of tumors. Here, we target unexplored skull base tumors using fast simultaneous two-channel stimulated scattering (SRS) new pseudo-hematoxylin eosin...
Abstract Background Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an “abscopal effect,” whereby unirradiated neoplastic cells outside sites are recognized attacked by the immune system. Radiation combined with anti–programmed cell death ligand 1 (PD-L1) demonstrated modest efficacy in phase II human glioblastoma trials, but mechanism relevance of abscopal effect during this response remain unknown. Methods We...