A5015250851- NF-κB Signaling Pathways
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Sepsis Diagnosis and Treatment
- T-cell and B-cell Immunology
- Trace Elements in Health
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Bioactive Compounds and Antitumor Agents
- Natural product bioactivities and synthesis
- Cell death mechanisms and regulation
- Diabetes and associated disorders
- Fatty Acid Research and Health
- DNA and Nucleic Acid Chemistry
- Electrolyte and hormonal disorders
- Immune Response and Inflammation
- Metabolomics and Mass Spectrometry Studies
- Acute Kidney Injury Research
- Histone Deacetylase Inhibitors Research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Cardiac Valve Diseases and Treatments
- Cardiac and Coronary Surgery Techniques
- Signaling Pathways in Disease
- DNA Repair Mechanisms
- Viral Infections and Immunology Research
Instituto Gulbenkian de Ciência
2019-2025
University of Lisbon
2025
CeMM Research Center for Molecular Medicine
2014-2019
Austrian Academy of Sciences
2014-2019
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
2016-2019
Medical University of Vienna
2016
IFOM
2012
Cancer Research UK
2010
Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, identify a biallelic mutation MAP3K14 gene encoding NIK (NF-κB-inducing kinase). Loss kinase activity mutant NIK, predicted by silico analysis confirmed functional assays, leads to defective activation both canonical non-canonical NF-κB signalling. Patients mutated exhibit B-cell...
Several classes of antibiotics have long been known to beneficial effects that cannot be explained strictly on the basis their capacity control infectious agent. Here, we report tetracycline antibiotics, which target mitoribosome, protected against sepsis without affecting pathogen load. Mechanistically, found mitochondrial inhibition protein synthesis perturbed electron transport chain (ETC) decreasing tissue damage in lung and increasing fatty acid oxidation glucocorticoid sensitivity...
Antibody diversification requires the DNA deaminase AID to induce instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, single-stranded and needs gain access Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated characterized endogenous AID-containing protein complexes from chromatin of diversifying cells. The majority proteins associated belonged polymerase elongation modification...
Polymerase δ is essential for eukaryotic genome duplication and synthesizes DNA at both the leading lagging strands. The polymerase complex a heterotetramer comprising catalytic subunit POLD1 accessory subunits POLD2, POLD3, POLD4. Beyond replication, has emerged as central element in maintenance. essentiality of constrained generation δ–knockout cell lines or model organisms and, therefore, understanding complexity its activity function subunits. To our knowledge, no germline biallelic...
Regulation of cell and tissue homeostasis by programmed death is a fundamental process with wide physiological pathological implications. The advent scalable somatic genetic technologies creates the opportunity to functionally map such essential pathways, thereby identifying potential disease-relevant components. We investigated basis underlying necroptotic performing complementary set loss-of-function gain-of-function screens. To this end, we established FADD-deficient haploid human KBM7...
Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning eviction of histones select sites in genome. Here, we show that extensively anthracyclines Doxorubicin, Daunorubicin, Epirubicin decrease transcription nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon-responsive genes primary mouse (Mus musculus) macrophages. Using an NMR-based structural...
Sepsis is a leading cause of death in Intensive Care Units. Despite its prevalence, sepsis remains insufficiently understood, with no substantial qualitative improvements treatment the past decades. Immunomodulatory agents may hold promise, given significance TNF-α and IL-1β as mediators. This study examines immunomodulatory effects moxifloxacin, fluoroquinolone utilized clinical practice. THP1 cells were treated vitro either PBS or moxifloxacin subsequently challenged lipopolysaccharide (LPS)
NF-κB signaling is a central pathway of immunity and integrates signal transduction upon wide array inflammatory stimuli. Noncanonical activated by small subset TNF family receptors characterized NF-κB2/p52 transcriptional activity. The medical relevance this has recently re-emerged from the discovery primary immunodeficiency patients that have loss-of-function mutations in MAP3K14 gene encoding NIK. Nevertheless, knowledge protein interactions regulate noncanonical sparse. Here we report...
Summary Synergy of resistance and disease tolerance mechanisms is necessary for an effective immune response leading to survival return homeostasis when organism challenged by infection. Antibiotics are used their enhancement capabilities decreasing pathogen load, but several classes have long been known beneficial effects that cannot be explained strictly on the basis capacity control infectious agent. Here we report tetracycline antibiotics, a class ribosome-targeting drugs, robustly...
ABSTRACT Regulation of cell and tissue homeostasis by programmed death is a fundamental process with wide physiological pathological implications. The advent scalable somatic genetic technologies creates the opportunity to functionally map these essential pathways, thereby identifying potential disease-relevant components. We investigated basis underlying necroptotic performing complementary set loss- gain-of-function screens. To this end, we established FADD -deficient haploid human KBM7...
Abstract Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning eviction of histones select sites in genome. Here we show that extensively anthracyclines Doxorubicin, Daunorubicin Epirubicin, decrease transcription nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon responsive genes. Using an NMR-based structural approach, demonstrate disturb...
OBJECTIVES: Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only number of platelets decreases, but also remaining are functionally impaired. Although lipid metabolism crucial for platelet function, little known regarding metabolic changes CPB-dysfunction. Our aim to explore possible contribution perturbations dysfunction after cardiac surgery. DESIGN: Prospective...
Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning eviction of histones select sites in genome. Here we show that extensively anthracyclines Doxorubicin, Daunorubicin Epirubicin, decrease transcription nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon responsive genes. Using an NMR-based structural approach, demonstrate disturb complexes formed...