A5035634149- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Innovations in Medical Education
- CAR-T cell therapy research
- Health and Wellbeing Research
- Virus-based gene therapy research
- Cancer survivorship and care
- Global Health Workforce Issues
- Hepatitis C virus research
- LGBTQ Health, Identity, and Policy
- Immunotherapy and Immune Responses
- Immune cells in cancer
- African Sexualities and LGBTQ+ Issues
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Interprofessional Education and Collaboration
- Family Support in Illness
- Clinical Reasoning and Diagnostic Skills
- Cytomegalovirus and herpesvirus research
- Names, Identity, and Discrimination Research
- CRISPR and Genetic Engineering
- Primary Care and Health Outcomes
- Lung Cancer Research Studies
University College London
2018-2025
Institute of Infection and Immunity
2024-2025
Royal Australian College of General Practitioners
2024
The University of Queensland
2024
Roland Hill (United Kingdom)
2024
The Royal Free Hospital
2018-2022
University of British Columbia
2015-2020
Office of Diversity and Inclusion
2020
CD28 and CTLA-4 (CD152) play essential roles in regulating T cell immunity, balancing the activation inhibition of responses, respectively. Although both receptors share same ligands, CD80 CD86, specific requirement for two distinct ligands remains obscure. In present study, we demonstrate that, although targets CD86 destruction via transendocytosis, this process results separate fates itself. presence CD80, remained ligand bound, was ubiquitylated trafficked late endosomes lysosomes....
CD80 and CD86 are expressed on antigen presenting cells required to engage their shared receptor, CD28, for the costimulation of CD4 T cells. It is unclear why two stimulatory ligands with overlapping roles have evolved. also bind regulatory molecule CTLA-4. We explored role in homeostasis proliferation CD4+FoxP3+ (Treg), which constitutively express high levels CTLA-4 yet critically dependent upon CD28 signals. observed that was dominant ligand Treg proliferation, survival, maintenance a...
Abstract CTLA‐4 and PD‐1 are key immune checkpoint receptors that targeted in the treatment of cancer. A recently identified physical interaction between respective ligands, CD80 PD‐L1, has been shown to block PD‐L1/PD‐1 binding prevent PD‐L1 inhibitory functions. Since is known capture degrade its ligands via transendocytosis, we investigated interplay transendocytosis CD80/PD‐L1 interaction. We find results a time‐dependent recovery availability correlates with removal. Moreover, highly...
Heterozygous mutations in CTLA-4 result an inborn error of immunity with autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications allogeneic hematopoietic stem transplantation. Here, we designed homology-directed repair (HDR) editing strategy that inserts cDNA into first intron genomic locus primary human cells. This resulted regulated expression CD4 + cells, functional studies demonstrated CD80 CD86...
CTLA-4 is an essential regulator of T-cell immune responses whose intracellular trafficking a hallmark its expression. Defects in due to LRBA deficiency cause profound autoimmunity humans. rapidly internalizes via clathrin-dependent pathway followed by poorly characterized recycling and degradation fates. Here, we explore the impact manipulating Rab GTPases on expression determine how these proteins affect trafficking. We observe that distributed across several compartments marked Rab5, Rab7...
Abstract Manipulating CD28 co-stimulation is a key element of anti-tumour immune responses and treating autoimmune diseases. can reduce the T cell activation threshold but has complex relationship with TCR signalling an unclear role in specific subsets. Using series vitro stimulation assays, we have studied relative contribution signals human CD4+ responses. We show that not only quantity co-stimulation, also its intensity to differentially impacts division Naïve Memory cells. independent...
This study explored the perspectives and experiences of breast cancer patients medical oncologists with regards to participation in a lifestyle intervention at tertiary treatment center. A thematic approach was used understand context within which recommended experienced, inform future programming promote uptake. Twelve women receiving adjuvant chemotherapy eight completed interviews. Findings suggest prescription for from trusted health professional influential cancer. The offered physical,...
General practitioner (GP) training in Australia relies on accredited GP supervisors facilitating workplace-based for registrars. There is a shortage of that likely to worsen. This research aimed elucidate the perspectives early-career GPs and rural generalists (RGs) about barriers, motivators enablers becoming supervisor.
Abstract The CTLA-4 and PD-1 checkpoints control immune responses to self-antigens are key targets in cancer immunotherapy. Both pathways connected via a cis interaction between CD80 PD-L1, the ligands for respectively. This prevents binding PD-L1 but is reversed by trans-endocytosis of CD80. However, mechanism which selectively removes not unclear. Here we show that – interactions unimpeded with does displace per se. Rather, both rigidity bivalency WT molecule required orientate such no...
The CTLA-4 and PD-1 checkpoints control immune responses to self-antigens andare key targets in cancer immunotherapy. Both pathways are connected via a cisinteraction between CD80 PD-L1, the ligands for respectively.This cis interaction prevents binding PD-L1 but is reversed by transendocytosisof CD80. However, mechanism which selectively removesCD80 not unclear. Here we show that – interactions areunimpeded with does displace PD-L1per se. Rather, both rigidity bivalency of WT molecule...
There is widespread agreement about the importance of direct observation trainee practice by clinical supervisors. Less known observers external to supervisory team. We explored educational affordances GP consultations for and assessment purposes, from perspectives both trainees.GP medical educators, who were scheduled observe sessions consultations, recruited as participant observers. They completed field notes, reflective memos a focus group discussion, conducted post-observation...
Abstract CTLA-4 and PD-1 are key immune checkpoints that targeted in the treatment of cancer. Recently it has emerged there is a physical interaction between ligands these pathways (CD80 PD-L1), which can prevent PD-L1 inhibitory functions. Since captures degrades its via transendocytosis, we investigated how transendocytosis CD80 impacted by interaction. We find results time-dependent recovery availability correlates with removal. Moreover, highly specific only removed, heterodimeric...
Background: Heterozygous mutations in CTLA4 result an inborn error of immunity (IEI) (also known as primary immunodeficiency) with a severe clinical phenotype. Autologous T cell gene therapy may offer cure without the immunological complications allogeneic stem transplantation. The mutational landscape and requirement for tight regulation make viral addition approaches unappealing. Gene editing strategies permit alteration while retaining endogenous control machinery. Aims: We set out to...