A5087057600- Virus-based gene therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
- Retinal Development and Disorders
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Immunology Research
- Telomeres, Telomerase, and Senescence
- Cytokine Signaling Pathways and Interactions
- Genetics, Bioinformatics, and Biomedical Research
- Immunodeficiency and Autoimmune Disorders
- Epigenetics and DNA Methylation
- Immune responses and vaccinations
- Retinoids in leukemia and cellular processes
- Viral gastroenteritis research and epidemiology
- Animal Genetics and Reproduction
- Immune cells in cancer
- Retinal Diseases and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hematopoietic Stem Cell Transplantation
- Chemokine receptors and signaling
- Inflammasome and immune disorders
Sirius University of Science and Technology
2023-2024
University College London
2022-2023
University of Lisbon
2017-2022
Instituto de Medicina Molecular João Lobo Antunes
2018
University of St Andrews
2013-2015
Queen's University Belfast
2007-2010
University of Würzburg
2006
Replication of the giant RNA genome severe acute respiratory syndrome (SARS) coronavirus (CoV) and synthesis as many eight subgenomic (sg) mRNAs are mediated by a viral replicase-transcriptase outstanding complexity that includes an essential endoribonuclease activity. Here, we show CoV replicative machinery, unlike other viruses, also uses exoribonuclease (ExoN) activity, which is associated with nonstructural protein (nsp) 14. Bacterially expressed forms SARS-CoV nsp14 were shown to act on...
Abstract Regulatory T cells (Treg) play a critical role in immune tolerance. The scarcity of Treg therapy clinical trials humans has been largely due to the difficulty obtaining sufficient numbers. We performed preclinical investigation on potential mesenchymal stromal (MSCs) expand vitro support future trials. Human peripheral blood mononuclear from healthy donors were cocultured with allogeneic bone marrow-derived MSCs expanded under xenogeneic-free conditions. Our data show an increase...
The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified novel heterozygous germline mutation c.1255G > C, p.D419H leading to overactivity JAK/STAT pathway, in kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis follicular lymphoma. D419H expression functional activity...
Many biomedical applications absolutely require, or are substantially enhanced by, coexpression of multiple proteins from a single vector. Foot-and-mouth disease virus 2A (F2A) and “2A-like” sequences (e.g., Thosea asigna 2A; T2A) used widely for this purpose since can be coexpressed by linking open reading frames (ORFs) to form cistron. The activity F2A “cleavage” may, however, compromised both the use shorter versions (derived multiple-purpose cloning sites) link upstream protein. To...
Many biomedical applications require the expression or production of therapeutic hetero-multimeric proteins/protein complexes: in most cases only accomplished by co-ordinated co-expression within same cell. Foot-and-mouth disease virus 2A (F2A) and '2A-like' sequences are now widely used for this purpose. Since mediates a co-translational 'cleavage' at its own C-terminus, encoding multiple proteins (linked via 2As) can be concatenated into single ORF: transgene. It has been shown that some...
ABSTRACT Expression of the exceptionally large RNA genomes CoVs involves multiple regulatory mechanisms, including extensive proteolytic processing replicase polyproteins, pp1a and pp1ab, by two types cysteine proteases: chymotrypsin-like main protease papain-like accessory proteases (PL pro s). Here, we characterized human coronavirus 229E (HCoV-229E) amino-proximal pp1a/pp1ab region paralogous PL activities. Reverse-genetics data revealed that replacement PL2 active-site was lethal. By...
Purpose Janus kinase-1 (JAK1) tyrosine kinase mediates signaling from multiple cytokine receptors, including interferon alpha/beta and gamma (IFN-α/β IFN-γ), which are important for viral mycobacterial protection respectively. We previously reported autosomal recessive (AR) hypomorphic JAK1 mutations in a patient with recurrent atypical infections relatively minor infections. This study tests the impact of partial deficiency on cellular responses to IFNs pathogen control. Methods...
Human regulatory CD4+CD25+FOXP3+ T cells (Treg) play important roles in the maintenance of self-tolerance and immune homeostasis various disease settings are also involved suppression effective responses. These heterogeneous phenotype function ability to reliably distinguish between FOXP3-expressing subpopulations can affect development successful therapies. This study demonstrates that hypomethylated CpG sites, present four regions FOXP3 locus, CAMTA1 FUT7 gene regions, be used subsets...
Anti-cancer therapy based on oncolytic viruses (OVs) is a targeted approach that takes advantage of OVs’ ability to selectively infect and replicate in tumor cells, activate the host immune response, destroy malignant cells over healthy ones. Vesicular stomatitis virus (VSV) known for its wide range advantages: lack pre-existing immunity, genome easily amenable manipulation, rapid growth high titers broad cell lines, name few. VSV-induced immunity can be enhanced by delivery...
The level of transduction efficiency the target retinal cells affects choice AAV serotype and outcome gene replacement therapy for inherited diseases. This study focused on tropism AAV2.7m8-, AAV5-, AAV8-, AAV9-GFP in ARPE-19 HEK293 cells. Fluorescence intensity was assessed bi-hourly by means IncuCyte S3 live imaging microscopy. Within 12 h, AAV2.7m8 demonstrated highest at four viral concentrations 1-, 3-, 6-, 8 × 104 VG/cell a dose-dependent manner, followed AAV5 AAV9 dose 6 21, 202, 323...
Adeno-associated virus (AAV)-based gene therapy has become one of the key directions modern translational medicine geared towards treatment hereditary disorders by means replacement. At moment, about 5,000 different syndromes are associated with mutations in large genes, which presents a great problem due to AAV packaging capacity 5 kilobases. The main strategies for overcoming this obstacle were creation truncated versions, overloading viral vector, and separate delivery partial genetic...
A substantial proportion (~39%) of all human proteins are either secreted from the cell, located within lumen/ membranes cytoplasmic vesicular structures, or, plasma membrane proteins. Given that such high initially translocated into endoplasmic reticulum (ER), many therapeutic strategies rely on ability to co-express multiple – some, or which, might be targeted sites. This directly applies in vivo gene therapy strategies, when may need co-expressed with selectable markers (e.g. ex...
Leber congenital amaurosis (LCA), one of the main causes blindness in children, accounts for at least 5 % all retinal dystrophies. To date, 26 LCA-causing genes (mostly inherited an autosomal recessive manner) with more than 400 mutations have been identified [1]. Defects Retinol Dehydrogenase 12 (RDH12), NADPH-dependent reductase displaying high activity toward 9-cis and all-trans-retinol participating metabolism short-chain aldehydes, cause LCA type Retinitis Pigmentosa 53 [2].
Abstract Evidence is now emerging that the evolutionarily conserved septin family of genes are contributors to diverse cellular processes including cytokinesis, apoptosis, actin and tubulin dynamics, endo exocytosis, membrane dynamics polarity. However their exact roles remain uncertain much remains be discovered about role in physiological pathological situations. Considerable data indicate septins implicated human neoplasia SEPT6 gene can a fusion partner MLL acute leukaemia. We...