Manuela Cominelli

ORCID: 0000-0002-4520-6104
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About
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Research Areas
  • Glioma Diagnosis and Treatment
  • MicroRNA in disease regulation
  • Hedgehog Signaling Pathway Studies
  • Cancer Cells and Metastasis
  • Circular RNAs in diseases
  • FOXO transcription factor regulation
  • Epigenetics and DNA Methylation
  • RNA Research and Splicing
  • Caveolin-1 and cellular processes
  • Cancer, Hypoxia, and Metabolism
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Bioinformatics and Genomic Networks
  • ATP Synthase and ATPases Research
  • Glycosylation and Glycoproteins Research
  • Tuberous Sclerosis Complex Research
  • 3D Printing in Biomedical Research
  • Gene expression and cancer classification
  • Inflammation biomarkers and pathways
  • Cell Adhesion Molecules Research
  • Renal and related cancers
  • Medicinal Plants and Neuroprotection
  • Neuroscience and Neuropharmacology Research
  • Liver physiology and pathology
  • Ferroptosis and cancer prognosis
  • T-cell and B-cell Immunology

University of Brescia
2015-2025

Brescia University
2023

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
2012-2021

Fondazione IRCCS Istituto Nazionale dei Tumori
2017

Stanford University
2017

Vita-Salute San Raffaele University
2010-2015

University of Insubria
2015

Columbia University Irving Medical Center
2015

IRCCS San Camillo Hospital
2015

Neuroscience Institute
2012

Abstract Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple cell subpopulations could be purified from the specimens patients with cancer stem (CSC) lines based on expression EGFR other putative CSC markers. All these are molecularly functionally distinct, tumorigenic, need to express...

10.1158/0008-5472.can-10-2353 article EN Cancer Research 2010-09-22

Glutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related higher tumor proliferation poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency patients with glioblastoma multiforme (GBM) who also developed epilepsy, which favorable prognostic factor glioma. Here, we investigated value expression GBM or without epilepsy its correlation survival. conducted clinical...

10.1093/neuonc/nos338 article EN Neuro-Oncology 2013-02-14

Glioblastoma (GBM) contains stem-like cells (GSCs) known to be resistant ionizing radiation and thus responsible for therapeutic failure rapidly lethal tumor recurrence. It is that GSC radioresistance relies on efficient activation of the DNA damage response, but mechanisms linking this response with stem status are still unclear. Here, we show MET receptor kinase, a functional marker GSCs, specifically expressed in subset radioresistant GSCs overexpressed human GBM recurring after...

10.15252/emmm.201505890 article EN cc-by EMBO Molecular Medicine 2016-04-04

The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition astrocyte-like, oligodendrocyte progenitor-like, cycling tumor subpopulations, a population enriched for ribosomal genes translation elongation factors primarily...

10.1016/j.xcrm.2023.101249 article EN cc-by-nc-nd Cell Reports Medicine 2023-10-25

Early B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of maturation. Originally described maturation, EBF1 was subsequently identified as crucial molecule for proper fate mesenchymal stem cells into adipocytes, osteoblasts muscle cells. In vessels, expression function have never been documented. Our data indicate that highly expressed peri-endothelial both tumor vessels physiological conditions....

10.1007/s00418-021-02015-7 article EN cc-by Histochemistry and Cell Biology 2021-07-16

Summary Tuberous sclerosis complex (TSC) is a dominantly inherited disease with high penetrance and morbidity, caused by mutations in either of two genes, TSC1 or TSC2. Most affected individuals display severe neurological manifestations – such as intractable epilepsy, mental retardation autism that are intimately associated peculiar CNS lesions known cortical tubers (CTs). The existence significant genotype-phenotype correlation bearing TSC2 highly controversial. Similar to observations...

10.1242/dmm.012096 article EN cc-by Disease Models & Mechanisms 2013-01-01

Achaete-scute homolog 1 gene (ASCL1) is a classifier for the proneural (PN) transcriptional subgroup of glioblastoma (GBM) that has relevant role in neuronal-like differentiation GBM cancer stem cells (CSCs) through activation PN signature. Besides prototypical ASCL1 target genes, molecular effectors mediating function regulating and, most relevantly, specification are currently unknown. Here we report not only promotes acquisition phenotype CSCs by inducing glial-to-neuronal lineage switch...

10.1038/s41418-018-0248-7 article EN cc-by Cell Death and Differentiation 2018-12-11

Abstract Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent unresolved enigma the field. We found significant neurological cognitive alterations untreated as well two groups short- long-term enzyme replacement with PEG-ADA. These included motor...

10.1038/srep40136 article EN cc-by Scientific Reports 2017-01-11

Lack of robust predictive biomarkers, other than MGMT promoter methylation, makes temozolomide responsiveness in newly diagnosed glioblastoma (GBM) patients difficult to predict. However, we identified with long-term survival (≥35 months) within a group GBM treated standard or metronomic adjuvant schedules. We thus investigated possible molecular profiles associated longer following treatment. the association features progression-free (PFS) and overall (OS). Human-derived cancer stem cells...

10.1093/jnci/djv041 article EN JNCI Journal of the National Cancer Institute 2015-03-04

microRNAs (miRNAs) are short noncoding RNAs, which regulate gene expression post-transcriptionally and play crucial roles in relevant biological pathological processes. Here, we investigated the putative role of miRNAs modulating tumor-initiating potential mouse medulloblastoma (MB)-derived cancer stem cells (CSCs). We first subjected bona fide highly tumorigenic (HT) CSCs as well lowly MB normal neural to miRNA profiling, identified a HT CSC-specific signature. Next, by cross-checking CSC...

10.1002/stem.1958 article EN Stem Cells 2015-01-31

Caveolin-1 (Cav-1) can ambiguously behave as either tumor suppressor or oncogene depending on its phosphorylation state and the type of cancer. In this study we show that Cav-1 was phosphorylated tyrosine 14 (pCav-1) by Src-kinase family members in various human cell lines primary mouse cultures rhabdomyosarcoma (RMS), most frequent soft-tissue sarcoma affecting childhood. overexpression embryonal RD alveolar RH30 cells yielded increased pCav-1 levels reinforced ERK AKT kinase, respectively,...

10.1371/journal.pone.0084618 article EN cc-by PLoS ONE 2014-01-10

In glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate–aspartate transporter expressed by astrocytes with role in uptake, is highly on the plasma membrane glioblastoma (GBM) cells, its expression significantly correlates shortened patient survival. Here, it was demonstrated that inhibition GLAST limited progression invasion GBM xenografts. Magnetic resonance spectroscopy used to measure GLAST‐expressing gliomas showing these tumors exhibit...

10.1002/ijc.31985 article EN International Journal of Cancer 2018-11-12

Glioblastoma (GBM) is the most malignant brain tumor of adults and characterized by extensive cell dissemination within parenchyma enhanced angiogenesis. Effective preclinical modeling these key features suffers from several shortcomings. Aim this study was to determine whether modulating expression extracellular matrix (ECM) modifiers in proneural (PN) mesenchymal (MES) cancer stem cells (CSCs) conventional glioma lines (GCLs) might improve invasion vascularization. To end, we selected...

10.1016/j.nbd.2019.104705 article EN cc-by-nc-nd Neurobiology of Disease 2019-12-10

// Véronique Frattini 1,3 , Federica Pisati Maria Carmela Speranza Pietro Luigi Poliani 4 Gianmaria Frigé 3 Gabriele Cantini Dimos Kapetis 2 Manuela Cominelli Alessandra Rossi Gaetano Finocchiaro and Serena Pellegatta 1 Unit of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy Service Bioinformatics, Department Experimental Oncology, European Institute Oncology - Campus IFOM-IEO, Pathology, University Brescia, Correspondence: Pellegatta, email:...

10.18632/oncotarget.644 article EN cc-by Oncotarget 2012-09-22

Tuberous sclerosis complex (TSC) is a dominantly inherited disease caused by hyperactivation of the mTORC1 pathway and characterized development hamartomas benign tumors, including in brain. Among neurological manifestations associated with TSC, tumor progression static subependymal nodules (SENs) into giant cell astrocytomas (SEGAs) one major causes morbidity shortened life expectancy. To date, mouse modeling has failed reproducing these 2 lesions. Here we report that simultaneous Akt...

10.1172/jci96342 article EN Journal of Clinical Investigation 2018-02-01

The process of identifying and approving a new drug is time-consuming expensive procedure. One the biggest issues to overcome risk hepatotoxicity, which one main reasons for withdrawal from market. While animal models are gold standard in preclinical testing, translation results into therapeutic intervention often ambiguous due interspecies differences hepatic metabolism. discovery human induced pluripotent stem cells (hiPSCs) their derivatives has opened possibilities testing. We used...

10.3390/biomedicines11082114 article EN cc-by Biomedicines 2023-07-26

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to subclonal properties debated. In this study, we describe the systematic derivation, propagation, characterization GSCs from single, treatment-naive GBMs (GSC families). tumorigenic potential better correlates with its profile than make-up, classical being...

10.1016/j.celrep.2023.112816 article EN cc-by-nc-nd Cell Reports 2023-07-27

Progesterone (Pg) and estrogen (E) receptors (PgRs ERs) are expressed in normal neoplastic adrenal cortex, but their role is not fully understood. In literature, Pg demonstrated cytotoxic activity on AdrenoCortical Carcinoma (ACC) cells, while tamoxifen NCI-H295R cells. Here, we that ACC cell models, ERs were cells with a prevalence of ER- β over the α .Metastasis-derived MUC-1 ACC115m displayed very weak / signal, PgR expressed, although at low level. Accordingly, these latter resistant to...

10.3389/fendo.2021.669426 article EN cc-by Frontiers in Endocrinology 2021-04-26

Glioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism GBM offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers modalities by which different subgroups exploit rewiring sustain progression, we interrogated transcriptome, metabolome, glycoproteome human subgroup-specific sphere-forming cells (GSC). L-fucose abundance core fucosylation activation were elevated mesenchymal (MES)...

10.1158/0008-5472.can-22-0677 article EN Cancer Research 2022-11-21

Medulloblastoma arises from mutations occurring in stem/progenitor cells located restricted hindbrain territories. Here we report that the mouse postnatal ventricular zone lining IV ventricle also harbors bona fide stem that, remarkably, share same molecular profile with cerebellar white matter-derived neural (NSC). To identify novel mediators involved medulloblastomagenesis, compared these distinct hindbrain-derived NSC populations, which are potentially tumor initiating, murine compound...

10.1158/2159-8290.cd-11-0199 article EN Cancer Discovery 2012-05-04
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