A5079815463- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Neurogenesis and neuroplasticity mechanisms
- Cancer, Lipids, and Metabolism
- Immune cells in cancer
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- Lung Cancer Treatments and Mutations
- Neuroscience and Neuropharmacology Research
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- MicroRNA in disease regulation
- Advanced MRI Techniques and Applications
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- S100 Proteins and Annexins
- Lanthanide and Transition Metal Complexes
- Histone Deacetylase Inhibitors Research
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Liver physiology and pathology
Columbia University Irving Medical Center
2013-2025
Cancer Research Center
2019-2025
Columbia University
2009-2024
Oxford University Press (United Kingdom)
2020
University of Patras
2008
The Warburg effect is a tumor-related phenomenon that could potentially be targeted therapeutically. Here, we showed glioblastoma (GBM) cultures and patients' tumors harbored super-enhancers in several genes related to the effect. By conducting transcriptome analysis followed by ChIP-Seq coupled with comprehensive metabolite GBM models, found FDA-approved global (panobinostat, vorinostat) selective (romidepsin) histone deacetylase (HDAC) inhibitors elicited metabolic reprogramming concert...
Abstract Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable inhibiting via activity enzyme glutathione peroxidase 4 (GPX-4), generated directly from sulfur-containing amino acid cysteine, and indirectly methionine transsulfuration pathway. Herein we show that cysteine deprivation (CMD) can synergize with GPX4 inhibitor RSL3 to increase ferroptotic cell death in both murine human...
Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed reactive cells in brain tumor microenvironment. The distinct functions of various types likely lead to different requirements regulatory paradigms for Proneural gliomas can arise from transformation glial progenitors proliferate via mitogenic affects translation. To investigate translational regulation this...
Abstract We and others have shown that transition maintenance of biological states is controlled by master regulator proteins, which can be inferred interrogating tissue-specific regulatory models (interactomes) with transcriptional signatures, using the VIPER algorithm. Yet, some tissues may lack molecular profiles necessary for interactome inference (orphan tissues), or, as single cells isolated from heterogeneous samples, their tissue context undetermined. To address this problem, we...
Abstract Oligodendrocytes (OLs) are the myelin-forming cells of central nervous system. They derived from differentiation oligodendrocyte progenitors through a process requiring cell cycle exit and histone modifications. Here we identify arginine methyl-transferase PRMT5, molecule catalyzing symmetric methylation H4R3, as critical for developmental myelination. PRMT5 pharmacological inhibition, CRISPR/cas9 targeting, or genetic ablation decrease p53-dependent survival impair without...
Abstract Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay Transposase-Accessible Chromatin (ATAC-seq), proteomic and metabolite screening followed by carbon tracing extracellular flux analyses we show that genetic pharmacological AURKA inhibition elicits metabolic reprogramming mediated MYC targets concomitant...
The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with EGFR-mutant lung cancer, including those brain metastases. However, despite striking initial responses, osimertinib-treated eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory relapse is a major clinical challenge, its underlying mechanisms remain poorly understood. Using models of we...
Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition hyperphosphorylated tau in patient brains. However, mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses FTD brains with a stem cell culture and transplantation model FTD. We identified disease phenotypes neurons carrying MAPT-N279K mutation, which were related oxidative stress, phosphorylation, neuroinflammation upregulation...
Abstract While efforts to identify microglial subtypes have recently accelerated, the relation of transcriptomically defined states function has been largely limited in silico annotations. Here, we characterize a set pharmacological compounds that proposed polarize human microglia towards two distinct – one enriched for AD and MS genes another characterized by increased expression antigen presentation genes. Using different model systems including HMC3 cells, iPSC-derived cerebral organoids,...
The receptor kinase c-MET has emerged as a target for glioblastoma therapy. However, treatment resistance emerges inevitably. Here, we performed global metabolite screening with set enrichment coupled transcriptome and gene analysis proteomic screening, identified substantial reprogramming of tumor metabolism involving oxidative phosphorylation fatty acid oxidation (FAO) accumulation acyl-carnitines accompanied by an increase PGC1α in response to genetic (shRNA CRISPR/Cas9) pharmacologic...
Abstract Purpose: Cancer immunoediting shapes tumor progression by the selection of cell variants that can evade immune recognition. Given evasion and intratumor heterogeneity characteristic gliomas, we hypothesized CD8+ T cells mediate in these tumors. Experimental Design: We developed retrovirus-induced PDGF+Pten−/− murine gliomas evaluated glioma immunogenicity absence depleting this population. Furthermore, characterized genomic alterations present presence cells. Results: Upon...
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor, resection a key part of standard care. In fluorescence-guided surgery (FGS), fluorophores differentiate tumor tissue from surrounding normal brain. The heme synthesis pathway converts 5-aminolevulinic acid (5-ALA), fluorogenic substrate used for FGS, to fluorescent protoporphyrin IX (PpIX). resulting fluorescence believed be specific neoplastic glioma cells, but this specificity has not been examined at...
Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation an important diagnostic tool for tumor diagnosis and prognosis; however, its role glioma development, impact on response to therapy, not fully understood. We developed a murine model of proneural IDH1R132H-mutated that shows elevated production 2-hydroxyglutarate (2-HG) increased trimethylation lysine residue K27 histone H3 (H3K27me3) compared IDH1 wild-type tumors. found using...
Abstract Oligodendrocytes are the myelinating cells of central nervous system. Although CNS possesses ability to repair demyelinating insults, in certain cases, such as chronic lesions found multiple sclerosis, remyelination fails. Cycling capable becoming oligodendrocytes have been identified both developing and adult mammalian forebrain. Many studies focused on differences gene expression profiles oligodendrocyte progenitors differentiate into by isolating at different developmental stages...
In the adult mammalian brain, oligodendrocyte progenitors can differentiate into mature oligodendrocytes during remyelination. Mechanisms that regulate migration and differentiation of are great importance in understanding normal development demyelinating/remyelinating conditions. a microarray analysis comparing neonatal O4-positive (+) cells, we found tetraspanin KAI1/CD82 is far more highly expressed O4 + cells than (Lin et al., 2009). CD82 metastasis suppressor, its expression often...
Cerebral blood volume (CBV) is a hemodynamic correlate of oxygen metabolism and reflects brain activity function. High-resolution CBV maps can be generated using the steady-state gadolinium-enhanced MRI technique. Such technique requires an intravenous injection exogenous gadolinium based contrast agent (GBCA) recent studies suggest that GBCA accumulate in after frequent use. We hypothesize endogenous sources might exist within most conventional commonly acquired structural MRI, potentially...
Mechanisms that regulate oligodendrocyte (OL) precursor migration and differentiation are important in normal development demyelinating/remyelinating conditions. We previously found the tetraspanin CD82 is far more highly expressed O4(+) OL precursors of adult rat brain than those neonatal brain. has been physically linked to cMet, hepatocyte growth factor (HGF) receptor, tumor cells, this interaction decreases downstream signaling. show here inhibits HGF activation cMet precursors....
Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic in the microenvironment, including neurons. Neurons increasingly appreciated as important reactive components glioma due to their role causing hallmark symptoms, such cognitive deficits seizures, well potential ability drive progression. Separately, mTOR signaling has been shown have pleiotropic effects regulation neuronal...
Cortical interneurons establish inhibitory microcircuits throughout the neocortex and their dysfunction has been implicated in epilepsy neuropsychiatric diseases. Developmentally, migrate from a distal progenitor domain order to populate – process that occurs at slower rate humans than mice. In this study, we sought identify factors regulate of interneuron maturation across two species. Using embryonic mouse development as model system, found initiating migration is regulated by blood...
Abstract Diffusely infiltrating gliomas are known to cause alterations in cortical function, vascular disruption and seizures. These neurological complications present major clinical challenges, yet their underlying mechanisms causal relationships disease progression poorly characterized. Here, we followed glioma awake Thy1-GCaMP6f mice using in-vivo wide-field optical mapping monitor both neuronal activity functional hemodynamics. The bilateral synchrony of spontaneous glioma-infiltrated...