A5055035597- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Pluripotent Stem Cells Research
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Biomedical Ethics and Regulation
- vaccines and immunoinformatics approaches
- Renal and related cancers
- Monoclonal and Polyclonal Antibodies Research
- Hematopoietic Stem Cell Transplantation
- Immune Response and Inflammation
- Reproductive System and Pregnancy
- Cancer Immunotherapy and Biomarkers
- Renal Transplantation Outcomes and Treatments
- NF-κB Signaling Pathways
- Organ Donation and Transplantation
- Xenotransplantation and immune response
- Virus-based gene therapy research
- Tissue Engineering and Regenerative Medicine
- T-cell and Retrovirus Studies
- Immune responses and vaccinations
- Extracellular vesicles in disease
- Vascular Tumors and Angiosarcomas
University of Oxford
2012-2021
University of Calgary
2019
Hospital for Sick Children
2019
Medical Research Council
2019
Sir Robert McAlpine (United Kingdom)
2014
Roger Williams Medical Center
2010
Providence College
2010
Boston University
2010
University of Cambridge
1992-1996
John Radcliffe Hospital
1990-1995
Extracellular vesicles (EVs) are natural nanoparticles that mediate intercellular transfer of RNA and proteins great medical interest; serving as novel biomarkers potential therapeutic agents. However, there is little consensus on the most appropriate method to isolate high-yield high-purity EVs from various biological fluids. Here, we describe a systematic comparison between two protocols for EV purification: ultrafiltration with subsequent liquid chromatography (UF-LC) differential...
Infectious tolerance describes the process of CD4 + regulatory T cells (Tregs) converting naïve to become additional Tregs. We show that antigen-specific Tregs induce, within skin grafts and dendritic cells, expression enzymes consume at least 5 different essential amino acids (EAAs). fail proliferate in response antigen when any 1, or more, these EAAs are limiting, which is associated with a reduced mammalian target rapamycin (mTOR) signaling. Inhibition mTOR pathway by limiting EAAs,...
Although human embryonic stem (ES) cells may one day provide a renewable source of tissues for cell replacement therapy (CRT), histoincompatibility remains significant barrier to their clinical application. Current estimates suggest that surprisingly few lines be required facilitate rudimentary tissue matching. Nevertheless, the degree disparity between donor and recipient prove acceptable, extent matching is therefore required, remain unknown. To address this issue using mouse model CRT, we...
The peptide rAc1-11 represents the dominant T cell epitope of rat myelin basic protein (MBP) in mice H-2u haplotype. Residue 4 has been shown previously to govern binding class II molecule, I-Au. We have constructed analogues bearing amino acid substitutions at position and assessed their ability stimulate an antigen-specific hybridoma when presented by viable antigen presenting cells (APC). Complexes between I-Au one such analogue, rAc1-11[4A], were rapidly lost from surface live APC...
IL-18 (also known as IFN-gamma-inducing factor), although structurally unrelated to IL-12, shares with it the role of activating NK cells and polarizing T toward Th1 cell function. To understand how gene (and consequently function) is regulated, we have determined structure investigated mechanisms transcriptional control type expression. The mouse comprises seven exons distributed over 26 kb. Exons 1 2 this are 5'-noncoding exons. Promoter activity was detected upstream these noncoding in...
CD40 is a member of the tumor necrosis factor receptor superfamily. The interaction between and ligand (CD154) activates NF-κB, Jun N-terminal kinase, Janus kinase/signal transducers activators transcription pathways promotes B cell growth, differentiation, survival as well IL-12 production in macrophages dendritic cells. We demonstrate here existence multiple isoforms mRNA generated by alternative splicing show that their expression regulated differentially activated Pre-CD40 RNA spliced...
To investigate the antigen specificity of regulatory T cells capable preventing transplant rejection, we have developed two different strategies to achieve tolerance fully mismatched skin grafts in euthymic mice. A combination nondepleting Abs targeting CD4, CD8, and CD154 (CD40 ligand) induces dominant transplantation allografts. Such is antigen-specific, mediated by cells, can be extended through linked suppression naïve lymphocytes. The same protocol, when combined with allogeneic bone...
Abstract Transplants tolerated through a process known as infectious tolerance evoke continuous recruitment of regulatory T (Treg) cells that are necessary to maintain the unresponsive state. This state is maintained long-term and requires Ag exposure. It not known, however, whether operates sustained pre-existing cells, induction or both. Using mice deficient in natural Treg we show here quiescent donor dendritic (DC) laden with histocompatibility can induce de novo mediate transplantation...
The advent of induced pluripotent stem cells (iPSCs) has begun to revolutionize cell therapy by providing a convenient source rare types not normally available from patients in sufficient numbers for therapeutic purposes. In particular, the development protocols differentiation populations leukocytes as diverse naïve T cells, macrophages and Natural Killer (NK) provides opportunities their scale-up quality control prior administration. One population whose potential yet be explored is subset...
Abstract Regulatory CD4+ T cells are known to develop during the induction of donor-specific peripheral tolerance transplanted tissues; it is proposed that such a consequence persistent, danger-free stimulation by Ag. To test this hypothesis, male RAG-1−/− mice were recolonized with small numbers monospecific specific for H-2Ek-restricted Ag Dby. After 6 wk in environment, cells, having host, had become anergic vitro and acquired regulatory capacity. these expressed higher levels CTLA-4...
IL-12 is a heterodimer of two subunits, p35 and p40, encoded by separate genes that are regulated independently. To investigate the mechanisms underlying regulation gene, we characterized murine expression in B cell lymphoma line A20 bone marrow-derived dendritic cells. Multiple transcription start sites were identified both types, resulting four mRNA isoforms (types I-IV) differ number position upstream ATGs their 5' untranslated regions. In nonstimulated cells, predominant forms message II...