A5045485935- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Multiple Sclerosis Research Studies
- Immunodeficiency and Autoimmune Disorders
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Sphingolipid Metabolism and Signaling
- Growth Hormone and Insulin-like Growth Factors
- Rheumatoid Arthritis Research and Therapies
- Systemic Lupus Erythematosus Research
- Viral Infectious Diseases and Gene Expression in Insects
- Histone Deacetylase Inhibitors Research
- Virus-based gene therapy research
- FOXO transcription factor regulation
- Cholesterol and Lipid Metabolism
- Viral-associated cancers and disorders
- Chronic Lymphocytic Leukemia Research
- Autoimmune and Inflammatory Disorders Research
University College London
2014-2024
Sriwijaya University
2023
4D Pharma (United Kingdom)
2020-2021
University College Hospital
2018
Center for Rheumatology
2017
National Institutes of Health
2007-2012
Johns Hopkins University
2011-2012
National Human Genome Research Institute
2008-2012
Sidney Kimmel Comprehensive Cancer Center
2012
Johns Hopkins Medicine
2012
Summary Genetic alterations of the FOXN1 transcription factor, selectively expressed in thymic epithelia and skin, are responsible both mice humans for Nude/SCID phenotype. The first described human mutation was a C792T transition exon 5 resulting nonsense R255X, detected two probands originated from small community southern Italy. In this community, four additional children affected with congenital alopecia died early childhood because severe infections. study, we report on screening 30%...
The forkhead, Fox, gene family comprises a diverse group of ‘winged‐helix’ transcription factors that play important roles in development, metabolism, cancer and aging. Recently, several forkhead genes have been demonstrated to critical lymphocyte development effector functions. Alterations the FOXN1 both mice humans result severe combined immunodeficiency caused by an intrinsic defect thymus associated with congenital alopecia (Nude/severe phenotype). is member class proteins involved...
Background: Neutralizing anti-drug antibodies (ADA) can greatly reduce the efficacy of biopharmaceuticals used to treat patients with multiple sclerosis (MS). However, biological factors pre-disposing an individual develop ADA are poorly characterized. Thus, there is unmet clinical need for biomarkers predict development immunogenicity, and subsequent treatment failure. Up 35% MS treated beta interferons (IFNβ) ADA. Here we use machine learning immunogenicity against IFNβ utilizing serum...
Abstract Altered cholesterol, oxysterol, sphingolipid, and fatty acid concentrations are reported in blood, cerebrospinal fluid, brain tissue of people with relapsing-remitting multiple sclerosis (RRMS) linked to disease progression treatment responses. CD4 + T cells pathogenic RRMS, defective T-cell function could be mediated part by liver X receptors (LXRs)—nuclear that regulate lipid homeostasis immunity. RNA-sequencing pathway analysis identified genes within the ‘lipid metabolism’...
Mutations of the IL2RG encoding common gamma-chain (gamma(c)) lead to X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored immunological impairment in most treated patients, although lymphoproliferative events occurred five them. Even though two cases it was clearly documented an insertional mutagenesis LMO2, is conceivable that gamma(c) could have a role per se malignant lymphoproliferation. The shared cytokine receptor subunit, involved also growth...
The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and immunodeficiency. Hematopoietic cell transplantation can cure the disease gene therapy being tested as alternative treatment option. In this study, we assessed use of foamy virus (FV) vectors a transfer system for WAS, using Was knockout (KO) mouse model. Preliminary experiments FV expressing green fluorescent protein under transcriptional control endogenous WAS promoter or ubiquitously...
Patients deficient in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) are predisposed to varied autoimmunity, suggesting it has an important controlling role participating cells. IL-10-producing regulatory B (Breg) cells emerging as mediators of immunosuppressive activity. In experimental, antigen-induced arthritis WASp-deficient (WASp knockout [WAS KO]) mice developed exacerbated disease associated with decreased Breg and T (Treg) cells, but increased Th17 knee-draining...
Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β established treatment for MS; however, up 30% of IFN-β-treated MS patients develop neutralizing antidrug antibodies (nADA), reduced drug bioactivity efficacy. Mechanisms driving immunogenicity remain uncertain, reliable biomarkers predict development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14+ monocytes increased frequency...
Abstract We previously reported on an X-linked SCID (X-SCID) patient, who also had peripheral growth hormone (GH) hyporesponsiveness and abnormalities of the protein phosphorylation events following GH receptor (GHR) stimulation. In present study, we examined a potential role common cytokine γ-chain (γc) in GHR signaling using EBV-transformed lymphocytes from healthy subjects γc-negative X-SCID patients. demonstrated that proliferative response to stimulation B cell lines patients was...
Autoimmune lymphoproliferative syndrome is a disorder due to defect of lymphocyte apoptosis, whose clinical manifestations consist hyperplasia lymphoid tissues and autoimmune diseases. We report on 26-month-old child who presented with frequent eruptions weals angioedema without any apparent triggering factor, subsequently developed an erythematopapular rash histological pattern lymphoplasmacellular infiltrate. Familial anamnesis revealed history lymphoadenomegaly massive spleen liver...
An important goal for personalised treatment is predicting response to a particular therapeutic. A drawback of biological immunogenicity and the development antibodies directed against drug (anti-drug (ADA)), which are associated with poorer clinical outcome. Here we set out identify predictive biomarker that discriminates rheumatoid arthritis (RA) patients who more likely develop ADA in adalimumab, human monoclonal antibody tumor necrosis factor (TNF)α. By taking advantage an...
ABSTRACT Male and female immune responses are known to differ resulting in an increased prevalence of autoimmunity women. Here sex differences T-cell subset frequency function during adolescence were examined healthy donors patients with the autoimmune disease juvenile (J)SLE; onset JSLE commonly occurs puberty suggesting a strong hormonal influence. Healthy adolescent males had regulatory (Treg) frequency, Treg suppressive capacity IL-4 production compared females. The T-helper 2-like...
The Regulatory Myeloid Cells - International Immunopharmacology Conference in October 21-24, 2010 reviewed the recent advances our understanding of biological mechanisms expansion, activation, metabolism and T-cell suppression Derived Suppressor (MDSC). Lectures were focused on control microenvironment cytokines needed for myelopoiesis, interactions with neoplastic surrounding cells a negative immune control, role MDSC cancer promotion. complexity tumor opportunities therapeutic...
<h3>Background</h3> The gut microbiome has emerged as a promising innovative therapeutic target for immune-stimulation treatment of solid tumours. MRx0518 is novel, microbiome-derived oral live biotherapeutic. It potent anti-tumorigenic efficacy in the preclinical setting including murine models lung (LLC1), kidney (Renca) and breast (EMT6) cancer.<sup>1</sup> In these models, significant reduction tumour growth been demonstrated, induction immunostimulatory responses with infiltration NK...
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Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients relapsing remitting (RR)MS were recruited before (baseline), three, 12 (M12) months after commencing interferon-beta treatment. Neutralising ADA-status was determined at M12, patients stratified baseline according their M12...
Abstract Natural Tregs from both WAS patients and WASp-deficient (WKO) mice were previously reported as unable to suppress the proliferation of conventional T-cells in vitro. Because have a known defect IL-2 production this cytokine is important for generation Treg cells induced naïve T-cells, we assessed efficiency with which WKO can differentiate observed significant compared WT. Such was not corrected by increasing concentration anti-CD3 TGF-β. Preliminary experiments indicated role...