A5031194700- Cell death mechanisms and regulation
- interferon and immune responses
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Cancer-related Molecular Pathways
- Insect and Arachnid Ecology and Behavior
- Glioma Diagnosis and Treatment
- Plant and animal studies
- Insect and Pesticide Research
- DNA Repair Mechanisms
- Inflammasome and immune disorders
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bioactive Compounds and Antitumor Agents
- Phagocytosis and Immune Regulation
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Drug Transport and Resistance Mechanisms
- Bioactive Natural Diterpenoids Research
- Trypanosoma species research and implications
- Hippo pathway signaling and YAP/TAZ
- Toxin Mechanisms and Immunotoxins
- RNA Interference and Gene Delivery
- Circadian rhythm and melatonin
- Acute Lymphoblastic Leukemia research
Hospital Israelita Albert Einstein
2015-2024
Albert Einstein College of Medicine
2024
Hospital de Clínicas de Porto Alegre
2023
Insper
2019
St. Jude Children's Research Hospital
2011-2017
Universidade de São Paulo
2003-2011
Goethe University Frankfurt
2011
Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular
2010
Instituto Biológico
2002-2004
Significance Cell death by regulated necrosis causes tremendous tissue damage in a wide variety of diseases, including myocardial infarction, stroke, sepsis, and ischemia–reperfusion injury upon solid organ transplantation. Here, we demonstrate that an iron-dependent form necrosis, referred to as ferroptosis, mediates synchronized functional units diverse organs ischemia other stimuli, thereby triggering detrimental immune response. We developed novel third-generation inhibitor ferroptosis...
Regulated necrosis (RN) may result from cyclophilin (Cyp)D-mediated mitochondrial permeability transition (MPT) and receptor-interacting protein kinase (RIPK)1-mediated necroptosis, but it is currently unclear whether there one common pathway in which CypD RIPK1 act or separate RN pathways exist. Here, we demonstrate that necroptosis ischemia-reperfusion injury (IRI) mice occurs as primary organ damage, independent of the immune system, deficient for RIPK3, essential downstream partner are...
Abstract The Nlrp3 inflammasome is critical for host immunity, but the mechanisms controlling its activation are enigmatic. In this study, we show that loss of FADD or caspase-8 in a RIP3-deficient background, not RIP3 deficiency alone, hampered transcriptional priming and posttranslational canonical noncanonical inflammasome. Deletion presence absence inhibited caspase-1 caspase-11 by stimuli Nlrc4 addition, deletion prevented maturation, positioning upstream caspase-8. Consequently, FADD-...
Caspase-8, the initiator caspase of death receptor pathway apoptosis, its adapter molecule, FADD, required for caspase-8 activation, and cFLIPL, a caspase-8-like protein that lacks catalytic site blocks caspase-8-mediated are each essential embryonic development. Animals deficient in any these genes present with E10.5 lethality. Recent studies have shown development caspase-8-deficient mice is rescued by ablation RIPK3, kinase promotes form programmed, necrotic cell death. Here, we show...
To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored relevance T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for generation local antitumour immunity.We characterised functional states spatial organisation PDAC-infiltrating cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling microdissected TLSs, as well in vitro assays. In addition,...
BACKGROUND: The nuclear factor-kB (NF-kB) family of transcriptional regulators are central mediators the cellular inflammatory response. Although constitutive NF-kB signaling is present in most human tumours, mutations pathway members rare, complicating efforts to understand and block aberrant activity cancer. METHODS: To identify additional genetic alterations that drive ependymoma, we sequenced whole genomes (WGS) 41 tumours matched normal blood, transcriptomes (RNAseq) 77 tumours....
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent HCC development via proliferation- replication-associated DNA damage. Proliferation-associated replication stress, damage, genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels determine predict subsequent hepatocarcinogenesis. damage sensed by complex...
Tumor necrosis factor receptor (TNFR) signaling may result in survival, apoptosis or programmed necrosis. The latter is called necroptosis if the receptor-interacting protein 1 (RIP1) inhibitor necrostatin-1 (Nec-1) genetic knockout of RIP3 prevents it. In lethal mouse model TNFα-mediated shock, addition pan-caspase zVAD-fmk (zVAD) accelerates time to death. Here, we demonstrate that RIP3-deficient mice are protected markedly from shock presence and absence caspase inhibition. We further...
Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infants under 2 years old. Necroptosis has been implicated outcomes respiratory infections. We report that RSV infection triggers necroptosis primary mouse macrophages and human monocytes a RIPK1-, RIPK3- MLKL-dependent manner. Moreover, pathways are harmful to clearance from alveolar macrophages. Additionally, Ripk3 −/− mice were protected RSV-induced weight loss presented with reduced viral loads lungs. Alveolar...
Perturbation of the apoptosis and necroptosis pathways critically influences embryogenesis. Receptor-associated protein kinase-1 (RIPK1) interacts with Fas-associated via death domain (FADD)-caspase-8-cellular Flice-like inhibitory long (cFLIPL) to regulate both extrinsic necroptosis. Here, we describe Ripk1-mutant animals (Ripk1R588E [RE]) in which interaction between FADD RIPK1 is disrupted, leading embryonic lethality. This lethality not prevented by further removal kinase activity Ripk1...
Abstract Over the past 20 y, hormone melatonin was found to be produced in extrapineal sites, including cells of immune system. Despite increasing data regarding biological effects on regulation system, effect this molecule T cell survival remains largely unknown. Activation-induced death plays a critical role maintenance homeostasis system by eliminating self-reactive or chronically stimulated cells. Because activated not only synthesize but also respond it, we investigated whether could...