A5033124738- T-cell and B-cell Immunology
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Immune Response and Inflammation
- Multiple Sclerosis Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Immune Cell Function and Interaction
- Mesenchymal stem cell research
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Pluripotent Stem Cells Research
- Migraine and Headache Studies
- Long-Term Effects of COVID-19
- Myasthenia Gravis and Thymoma
- Alzheimer's disease research and treatments
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Systemic Lupus Erythematosus Research
- Cytokine Signaling Pathways and Interactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Renal Diseases and Glomerulopathies
- Neonatal Respiratory Health Research
- Nerve injury and regeneration
University of Zurich
2018-2025
Neuroscience Institute
2012-2018
San Raffaele University of Rome
2014-2018
Institute of Neuroimmunology of the Slovak Academy of Sciences
2017
Vita-Salute San Raffaele University
2011-2015
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2015
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2015
Abstract Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor variant III (EGFRvIII) alone fail...
Abstract Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers their undefined interactions 1,2 . Here we investigated peripheral immune signatures 61 monozygotic twin pairs discordant for MS to dissect influence predisposition factors. Using complementary multimodal high-throughput high-dimensional single-cell technologies in conjunction with data-driven computational...
Abstract Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated showing response. Modeling patient-individual resistance is challenging due the lack of predictive biomarkers and limited accessibility tissue for serial biopsies. Here, we investigate mechanisms anti-PD-1 anti-CTLA-4 therapy in syngeneic experimental gliomas show a clear dichotomy acquired heterogeneity ICB-responder non-responder tumors. We...
Abstract Oncogenic Ras mutations occur in various leukemias. It was unclear if, besides the direct transforming effect via constant RAS/MEK/ERK signaling, an inflammation-related of KRAS contributes to disease. Here, we identify a functional link between oncogenic Kras G12D and NLRP3 inflammasome activation murine human cells. Mice expressing active hematopoietic system developed myeloproliferation cytopenia, which is reversed mice lacking system. Therapeutic IL-1-receptor blockade or...
Allogeneic hematopoietic cell transplantation (allo-HCT) not only is an effective treatment for several hematologic malignancies but can also result in potentially life-threatening graft-versus-host disease (GvHD). GvHD caused by T cells within the allograft attacking nonmalignant host tissues; however, these same mediate therapeutic graft-versus-leukemia (GvL) response. Thus, there urgent need to understand how mechanistically uncouple GvL from GvHD. Using preclinical models of full and...
Abstract Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, cellular molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass spectral cytometry of blood thymus samples from patients in combination with supervised unsupervised machine-learning tools gain insight into immune...
Abstract Interleukin-12 (IL-12) is a potent driver of type 1 immunity. Paradoxically, in autoimmune conditions, including the CNS, IL-12 reduces inflammation. The underlying mechanism behind these opposing properties and involved cellular players remain elusive. Here we map receptor (IL-12R) expression to NK T cells as well neurons oligodendrocytes. Conditionally ablating IL-12R across cell types adult mice assessing their susceptibility experimental encephalomyelitis revealed that...
Background: Antibodies against aquaporin-4 (AQP4), a water channel particularly expressed on perivascular astrocytic podocytes, are proposed as marker for the diagnosis of neuromyelitis optica (NMO). However, consensus seroprevalence and optimal detection method has not yet been reached. Objectives: To investigate performance different assays to detect anti-AQP4 antibodies. Methods: We set up five assays. Two them were capable IgG reactivity brain tissue by immunofluorescence (NMO-IgG)....
GM-CSF in glomerulonephritis Despite being an immune-mediated disease, the contributions of individual immune cell types are not clear. To address this gap knowledge, Paust et al . characterized pathological cells samples from patients with and mice disease. The authors found that CD4+ T producing granulocyte-macrophage colony-stimulating factor (GM-CSF) licensed monocytes to promote disease by matrix metalloproteinase 12 disrupting glomerular basement membrane. Targeting inhibit axis...
In multiple sclerosis, the pathological interaction between autoreactive Th cells and mononuclear phagocytes in CNS drives initiation maintenance of chronic neuroinflammation. Here, we found that intrathecal transplantation neural stem/precursor (NPCs) mice with experimental autoimmune encephalomyelitis (EAE) impairs accumulation inflammatory monocyte-derived (MCs) CNS, leading to improved clinical outcome. Secretion IL-23, IL-1, TNF-α, cytokines required for terminal differentiation cells,...
Aspergillus fumigatus causes life-threatening mold pneumonia in immunocompromised patients, particularly those with quantitative or qualitative defects neutrophils. Whereas innate immune cell cross-talk licenses neutrophil antifungal activity the lung, role of epithelial cells this process is unknown. Here, we find that surfactant protein C (SPC)–expressing lung integrate infection-induced interleukin-1 and type III interferon signaling to produce granulocyte-macrophage colony-stimulating...
Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences immune response acute respiratory syndrome 2 remains unknown.Our aim was investigate complex interrelations comorbidities, response, and patient outcome in COVID-19.We used high-throughput, high-dimensional, single-cell mapping peripheral blood leukocytes algorithm-guided analysis.We discovered characteristic signatures associated not...
To track the effects of fingolimod, an approved drug for multiple sclerosis (MS), on activation myeloid cells from periphery to CNS.In vitro and ex vivo immunologic studies coupled with flow cytometry were performed evaluate action fingolimod lipopolysaccharide (LPS)-induced expression markers in human monocytes healthy participants, participants untreated MS, fingolimod-treated MS. In administration during experimental autoimmune encephalomyelitis (EAE) was established verify state splenic,...