Zev A. Binder
- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Neuroblastoma Research and Treatments
- Nanowire Synthesis and Applications
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Image Analysis Techniques
- Radiopharmaceutical Chemistry and Applications
- Brain Metastases and Treatment
- Advancements in Semiconductor Devices and Circuit Design
- Ferroptosis and cancer prognosis
- Cancer Research and Treatments
- Bone Tumor Diagnosis and Treatments
California University of Pennsylvania
2023-2025
University of Pennsylvania
2016-2025
Abramson Cancer Center
2024
Johns Hopkins Medicine
2010-2023
Johns Hopkins University
2010-2023
Champions Oncology (United States)
2023
Deoxi Biotecnologia (Brazil)
2023
Translational Therapeutics (United States)
2022
Memorial Sloan Kettering Cancer Center
2013
Ludwig Cancer Research
2013
Genomic analysis of a childhood cancer reveals markedly fewer mutations than what is typically seen in adult cancers.
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 Glioblastoma is the most common aggressive adult brain tumor. Numerous studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of: a) number of subjects, b) lack consistent acquisition protocol, c) quality, d) accompanying clinical, demographic, and molecular information. Toward alleviating these limitations, we contribute “University Pennsylvania Imaging, Genomics, Radiomics”...
We generated two humanized interleukin-13 receptor α2 (IL-13Rα2) chimeric antigen receptors (CARs), Hu07BBz and Hu08BBz, that recognized human IL-13Rα2, but not IL-13Rα1. Hu08BBz also canine IL-13Rα2. Both of these CAR T cell constructs demonstrated superior tumor inhibitory effects in a subcutaneous xenograft model glioma compared with EGFRvIII construct used recent phase 1 clinical trial (ClinicalTrials.gov: NCT02209376). The 75% reduction orthotopic growth using low-dose infusion. Using...
The remarkable heterogeneity of glioblastoma, across patients and over time, is one the main challenges in precision diagnostics treatment planning. Non-invasive vivo characterization this using imaging could assist understanding disease subtypes, as well risk-stratification planning glioblastoma. current study leveraged advanced analytics radiomic approaches applied to multi-parametric MRI de novo glioblastoma (n = 208 discovery, n 53 replication), discovered three distinct reproducible...
Therapeutic resistance remains a persistent challenge for patients with malignant tumors. Here, we reveal that endothelial cells (ECs) acquire transformation into mesenchymal stem cell (MSC)-like in glioblastoma (GBM), driving tumor to cytotoxic treatment. Transcriptome analysis by RNA sequencing (RNA-seq) revealed ECs undergo and stemness-like activation GBM microenvironment. Furthermore, identified c-Met-mediated axis induces β-catenin phosphorylation at Ser675 Wnt signaling activation,...
Abstract Purpose: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact cfDNA GBM, as well its role a surrogate tumor burden and substrate for next-generation sequencing (NGS). Experimental Design: conducted prospective cohort study 42 newly diagnosed GBM. Plasma was quantified at baseline prior initial resection longitudinally during chemoradiotherapy. association...
Bispecific T cell engagers (BiTEs) are bispecific antibodies that redirect cells to target antigen-expressing tumors. We hypothesized BiTE-secreting could be a valuable therapy in solid tumors, with distinct properties mono- or multi-valent strategies incorporating chimeric antigen receptor (CAR) cells. Glioblastomas represent good model for tumor heterogeneity, representing significant therapeutic challenge. detected expression of tumor-associated epidermal growth factor (EGFR), EGFR...
We analyze transposable elements (TEs) in glioblastoma (GBM) patients using a proteogenomic pipeline that combines single-cell transcriptomics, bulk RNA sequencing (RNA-seq) samples from tumors and healthy-tissue cohorts, immunopeptidomic samples. thus identify 370 human leukocyte antigen (HLA)-I-bound peptides encoded by TEs differentially expressed GBM. Some of the are repeat sequences intact open reading frames (ORFs) present up to several hundred recent long interspersed nuclear element...
Autologous chimeric antigen receptor (CAR) T cells targeted to epidermal growth factor variant III (CAR T-EGFRvIII) have been developed and administered experimentally treat patients with IDH1 wildtype recurrent glioblastoma (rGBM) (NCT02209376). We report the case of a 59-year-old patient who received single peripheral infusion CAR T-EGFRvIII survived 36 months after disease recurrence, exceeding expected survival for glioblastoma. Post-infusion histopathologic analysis tissue obtained...
Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, post-translational modifications (PTMs) with transcriptomic measurements uncover multi-scale regulatory interactions governing tumor development evolution. Applying 14 proteogenomic...
Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the and can be synaptically innervated by neurons, which drives tumor progression 1-6 . Synaptic inputs onto GBM cells identified so far are largely short-range glutamatergic 7-9 The extent of integration into brain-wide neuronal circuitry is not well understood. Here we applied rabies virus-mediated retrograde monosynaptic tracing approach 10-12 to systematically investigate circuit human organoids transplanted adult mice. We...
Non-invasive prognostic biomarkers to inform clinical decision-making are an urgent unmet need for the management of patients with glioblastoma (GBM). We previously showed that higher circulating cell-free DNA concentration [ccfDNA] is associated worse survival in GBM. However, biology underlying this unknown. prospectively enrolled 129 treatment-naïve GBM blood drawn prior initial resection (baseline) and at time first post-radiotherapy MRI. performed ccfDNA methylation deconvolution...
Glioblastoma multiforme (GBM) is a highly invasive and deadly brain tumor. Tumor cell invasion makes complete surgical resection impossible reduces the efficacy of other therapies. Genome-wide analyses mutations, copy-number changes, expression patterns have provided new insights into genetic abnormalities common in GBM. We analyzed published data identified motility pathways most frequently altered These were notably focal adhesion integrin signaling, extracellular matrix interactions...
Abstract The oncogene epidermal growth factor receptor variant III (EGFRvIII) is frequently expressed in glioblastomas (GBM) but its impact on therapy response still under controversial debate. Here we wanted to test if EGFRvIII influences the sensitivity towards alkylating agent temozolomide (TMZ). Therefore, retrospectively analyzed survival of 336 GBM patients, demonstrating that standard treatment, which includes TMZ, expression associated with prolonged survival, only patients...
Abstract Glioblastoma is a highly heterogeneous disease, with variations observed at both phenotypical and molecular levels. Personalized therapies would be facilitated by non-invasive in vivo approaches for characterizing this heterogeneity. In study, we developed unsupervised joint machine learning between radiomic genomic data, thereby identifying distinct glioblastoma subtypes. A retrospective cohort of 571 IDH-wildtype patients were included the pre-operative multi-parametric MRI scans...
// Chetan Bettegowda 1,2,* , Nishant Agrawal 2,3,* Yuchen Jiao 2,* Yuxuan Wang 2 Laura D. Wood 4 Fausto J. Rodriguez Ralph H. Hruban Gary L. Gallia 1 Zev A. Binder Callen Riggins Vafi Salmasi 5 Gregory Zachary Reitman 6 Ahmed Rasheed Stephen Keir Sueli Shinjo 7 Suely Marie Roger McLendon George Jallo Bert Vogelstein Darell Bigner Hai Yan Kenneth W. Kinzler and Nickolas Papadopoulos Department of Neurosurgery, Johns Hopkins University School Medicine, Baltimore, MD, USA Ludwig Center for...