A5053089505- Glioma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Cancer Cells and Metastasis
- Multiple Sclerosis Research Studies
- Cancer, Hypoxia, and Metabolism
- Herpesvirus Infections and Treatments
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Pituitary Gland Disorders and Treatments
- Hedgehog Signaling Pathway Studies
- Meningioma and schwannoma management
- Caveolin-1 and cellular processes
- Brain Metastases and Treatment
- Systemic Lupus Erythematosus Research
- Telomeres, Telomerase, and Senescence
- Adrenal and Paraganglionic Tumors
- RNA Research and Splicing
- Cancer, Stress, Anesthesia, and Immune Response
- Cytokine Signaling Pathways and Interactions
- Peripheral Neuropathies and Disorders
University of Brescia
2016-2025
IRCCS Ospedale San Raffaele
2025
Vita-Salute San Raffaele University
1998-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2023-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2024
Assistance Publique – Hôpitaux de Paris
2023
Brescia University
2008-2023
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
2006-2021
Fondazione IRCCS Istituto Nazionale dei Tumori
2002-2017
Stanford University
2015-2017
Microglia contribute to development, homeostasis, and immunity of the CNS. Like other tissue-resident macrophage populations, microglia express surface receptor triggering expressed on myeloid cells 2 (TREM2), which binds polyanions, such as dextran sulphate bacterial LPS, activates downstream signaling cascades through adapter DAP12. Individuals homozygous for inactivating mutations in TREM2 exhibit demyelination subcortical white matter a lethal early onset dementia known Nasu-Hakola...
Abstract In this study, cancer cells were isolated from tumor specimens of nine glioblastoma patients. Glioblastoma cells, cultured under suitable culture conditions, displayed markers typical neural stem capable partial multilineage differentiation in vitro, and gave origin to infiltrating tumors when orthotopically injected NOD/SCID mice. These although resistant freshly NK highly susceptible lysis mediated by both allogeneic autologous IL-2 (or IL-15)-activated cells. Indeed, all...
Abstract Cancer stem–like cells (CSC) could be a novel target for cancer therapy, including dendritic cell (DC) immunotherapy. To address this, we developed experiments aimed at DC targeting of neurospheres (NS) from GL261 glioma because can enriched in CSC. We obtained murine by growing epidermal growth factor/basic fibroblast factor without serum. GL261-NS recapitulated important features glioblastoma CSC and expressed higher levels radial glia stem markers than under standard conditions...
1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] inhibits production of IL-12, a cytokine involved in the development Th1 cells and pathogenesis Th1-mediated autoimmune diseases. Here, we show that 1,25(OH)(2)D(3) non-hypercalcemic analogue are selective potent inhibitors vitro vivo without inducing deviation to Th2 phenotype. Administration or its prevents chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35 - 55...
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...
T cell-mediated inflammation is considered to play a key role in the pathogenic mechanisms sustaining multiple sclerosis (MS). Caspase-1, formerly designated IL-1beta-converting enzyme, crucially involved immune-mediated because of its pivotal regulating cellular export IL-1beta and IL-18. We studied caspase-1 experimental autoimmune encephalomyelitis (EAE), animal model for MS. Caspase-1 transcriptionally induced during EAE, levels correlate with clinical course transcription rate...
Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).Twelve patients with cDGS underwent allogeneic cultured thymus.We sought to confirm and extend results previously obtained in single center.Two died pre-existing viral infections without having thymopoiesis, 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting graft loss need second transplant. Evidence...
Lrrc8a is a ubiquitously expressed gene that encodes leucine-rich repeat (LRR)–containing protein detected at higher levels on the surface of thymocytes than other immune cells. We generated Lrrc8a−/− mice to investigate role LRRC8A in lymphocyte development and function. had increased prenatal postnatal mortality, growth retardation, multiple tissue abnormalities. displayed modest block B cell but intact intrinsic In contrast, both Lrrc8a−/−→Rag2−/− bone marrow chimeras exhibited severe...
The thymus plays a fundamental role in establishing and maintaining central peripheral tolerance defects thymic architecture or AIRE expression result the development of autoreactive lymphocytes. Patients with partial DiGeorge Syndrome (DGS) Down (DS) present alterations size higher risk to develop autoimmunity. We sought evaluate thymocyte DGS DS patients determine extent which immune dysregulation T cell homeostasis perturbation these patients. Thymi from pediatric age-matched controls...
Abstract The exclusive detrimental role of proinflammatory cytokines in demyelinating diseases the CNS, such as multiple sclerosis, is controversial. Here we show that intrathecal delivery an HSV-1-derived vector engineered with mouse IFN-γ gene leads to persistent (up 4 wk) CNS production and inhibits course a chronic-progressive form experimental autoimmune encephalomyelitis (EAE) induced C57BL/6 mice by myelin oligodendrocyte glycoprotein (MOG)35–55. Mice treated IFN-γ-containing before...
F. Orzan, S. Pellegatta, P. L. Poliani, Pisati, V. Caldera, Menghi, D. Kapetis, C. Marras, Schiffer and G. Finocchiaro (2011) Neuropathology Applied Neurobiology37, 381–394 Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas glioma stem-like cells Aims: Proteins the Polycomb repressive complex (PRC2) are epigenetic gene silencers involved tumour development. Their oncogenic function might be associated with their role stem cell maintenance. The histone methyltransferase a key...
Rag enzymes are the main players in V(D)J recombination, process responsible for rearrangement of TCR and Ig genes. Hypomorphic mutations humans, which maintain partial activity, cause a peculiar SCID associated with autoimmune-like manifestations, Omenn syndrome (OS). Although deficient ability to sustain thymopoiesis produce diverse T B cell repertoire explains increased susceptibility severe infections, molecular cellular mechanisms underlying spectrum clinical immunological features OS...
The contribution of B cells to the pathology Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model SCID with homozygous Rag1 S723C mutation that impairs, but does abrogate, V(D)J recombination activity. In spite block at pro–B cell stage profound lymphopenia, significant serum levels immunoglobulin (Ig) G, IgM, IgA, IgE high proportion Ig-secreting were detected in mice. Antibody responses trinitrophenyl...