Towards an integrated understanding of the CD28/CTLA4 immune checkpoint in the regulation of autoimmunity
Lead Research Organisation:
University College London
Department Name: Immunology and Molecular Pathology
Abstract
The immune system contains a number of powerful weapons that defend us from constant attacks by microbes that threaten our health. Unfortunately, like any complex system it sometimes goes wrong and instead of defending us, can attack our own body and cause damage. Such "collateral damage" is what causes autoimmune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis: the weapons responsible are part of our immune army performing their normal jobs, just in the wrong place at the wrong time. The key weapon that starts the autoimmune attack in these diseases is called a T cell. When scientists explored which genes are responsible for autoimmune diseases, they identified a strong bias towards genes that tell our T cells to fire or affect their ability to stop firing. Careful experiments using animal models have also shown that it is possible to cause autoimmune diseases just by transferring T cells from one mouse to another. This provides strong evidence that T cells are critical players in determining whether a person develops an autoimmune disease.
Properly understanding the signals that tell T cells to fire or cease firing is therefore critical to understanding and treating many autoimmune diseases. A precise system involving 4 molecular switches is used to make this decision. Two of these switches (CD28 and CTLA4) are receptors expressed on the T cell and these interact with 2 binding partners (CD80 and CD86) expressed on other cells. Correct use of these 4 molecules can mean the difference between life and death. Without CD28 immune responses cannot be mounted properly and without CTLA4 the immune response fires indiscriminately causing lethal inflammation. Whilst it is very clear that CD28 promotes immune responses and CTLA4 inhibits them, why these opposing switches share the same triggers (CD80 and CD86) is a complete mystery. At face value, it would seem more intuitive to have one binding partner to engage CD28 (the on switch) and another to engage CTLA4 (the off switch). However both CD80 and CD86 can bind to both CD28 and CTLA4. How then does the immune system decide whether CD28 or CTLA4 wins out?
Recent work from our groups has made substantial progress in understanding this system. We discovered that CTLA4 works by hoovering up CD80 and CD86 thereby preventing CD28 from being triggered. Such a model is fundamentally different to previous ideas and explains many features of the system that until now did not make sense. Viewing the system in this way prompts us to ask different questions: Why are there 2 binding partners? Are they both equivalently hoovered up by CTLA4? Do both take the same amount of time to be re-expressed after removal? What does this mean for the control of immune responses? In this proposal we will address these and other questions to generate a detailed understanding of this important system and use this knowledge to come up with new ideas for immune therapies. What we learn in this project will be of direct relevance to a wide variety of immune mediated conditions from autoimmunity to cancer and vaccination to organ transplantation.
Properly understanding the signals that tell T cells to fire or cease firing is therefore critical to understanding and treating many autoimmune diseases. A precise system involving 4 molecular switches is used to make this decision. Two of these switches (CD28 and CTLA4) are receptors expressed on the T cell and these interact with 2 binding partners (CD80 and CD86) expressed on other cells. Correct use of these 4 molecules can mean the difference between life and death. Without CD28 immune responses cannot be mounted properly and without CTLA4 the immune response fires indiscriminately causing lethal inflammation. Whilst it is very clear that CD28 promotes immune responses and CTLA4 inhibits them, why these opposing switches share the same triggers (CD80 and CD86) is a complete mystery. At face value, it would seem more intuitive to have one binding partner to engage CD28 (the on switch) and another to engage CTLA4 (the off switch). However both CD80 and CD86 can bind to both CD28 and CTLA4. How then does the immune system decide whether CD28 or CTLA4 wins out?
Recent work from our groups has made substantial progress in understanding this system. We discovered that CTLA4 works by hoovering up CD80 and CD86 thereby preventing CD28 from being triggered. Such a model is fundamentally different to previous ideas and explains many features of the system that until now did not make sense. Viewing the system in this way prompts us to ask different questions: Why are there 2 binding partners? Are they both equivalently hoovered up by CTLA4? Do both take the same amount of time to be re-expressed after removal? What does this mean for the control of immune responses? In this proposal we will address these and other questions to generate a detailed understanding of this important system and use this knowledge to come up with new ideas for immune therapies. What we learn in this project will be of direct relevance to a wide variety of immune mediated conditions from autoimmunity to cancer and vaccination to organ transplantation.
Technical Summary
This programme is focused on understanding how the T cell molecules CD28 and CTLA4 dictate control of tolerance versus immunity, an area of profound importance in immunology. Whilst their involvement is understood in broad principle, the mechanistic details of how the system actually works have not been established and will be crucial for sophisticated manipulation of the immune response. We recently identified a mechanism of action for CTLA4 (transendocytosis) where its inhibitory function is linked to physical destruction of its ligands (CD80 and CD86). Since CD28 binds to the same ligands, CTLA4 controls CD28 engagement. This model generates an integrated view in which the function of each individual molecule must be understood in the context of the other three players. This also leads to an emphasis on the regulation of CD80/CD86 expression and re-expression as the arbiters of immune outcome. Surprisingly, despite the fundamental importance of these ligands in driving immune responses, regulation of their expression is still poorly understood. Furthermore, the rationale for having two biophysically distinct ligands is entirely unclear.
It is our contention that a transendocytosis perspective holds the key to understanding why two ligands exist. We will therefore carefully evaluate the differences in the control of their expression, and establish the capacity of each ligand to stimulate responses via CD28 as well as be regulated via CTLA4 transendocytosis. We will use novel mouse models to dissect whether differences between ligand function in vivo reflect inherent functional properties or distinct expression patterns. By utilising a combination of molecular and cellular in vitro and in vivo approaches we will provide new insights into an area of fundamental importance to immunology. This will result in a more complete and predictive understanding of this crucial immune checkpoint enabling us to conceive and test novel therapeutic strategies.
It is our contention that a transendocytosis perspective holds the key to understanding why two ligands exist. We will therefore carefully evaluate the differences in the control of their expression, and establish the capacity of each ligand to stimulate responses via CD28 as well as be regulated via CTLA4 transendocytosis. We will use novel mouse models to dissect whether differences between ligand function in vivo reflect inherent functional properties or distinct expression patterns. By utilising a combination of molecular and cellular in vitro and in vivo approaches we will provide new insights into an area of fundamental importance to immunology. This will result in a more complete and predictive understanding of this crucial immune checkpoint enabling us to conceive and test novel therapeutic strategies.
Planned Impact
In addition to serving the academic community, there are several wider benefits of our research.
Benefits to industry
The ability to modulate the immune system in a predictable way is a major goal of the pharmaceutical industry. The molecules which are the focus of this research programme (CD28, CTLA4, CD80, CD86) are widely recognized to play pivotal roles in the initiation and suppression of immune responses and as such have attracted considerable interest from pharmaceutical companies. Drugs to enhance the immune response can be used to fight cancer while drugs that suppress immunity can be used to treat autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis. However, effective use of these drugs depends on an accurate understanding of the biological function of each of these molecules. The results from this research are therefore likely to be of high value to the pharmaceutical industry and may lead to new drugs to target the CD28/CTLA4 pathway or to existing ones being used in different ways and in novel combinations.
Benefits to patients
A better understanding of how to control the immune system through the CD28/CTLA4 pathway promises to offer significant benefits for patient groups, particularly those with autoimmunity. Our recent work has shown that CTLA4 mutations in humans are associated with defective regulatory T cell function and an autoimmune syndrome (Nature Medicine, 2014) providing direct evidence of the critical importance of this pathway in humans. This prompts consideration of new therapeutic approaches in these patients and has already informed clinical decision making for some of these individuals. Further understanding of how this pathway works will therefore improve our ability to regulate autoimmunity. Given that the CD28/CTLA4 pathway is a major control point for immunity, relevant to a wide range of diseases, our research has the potential to bring health benefits to a large number of individuals.
Impact on Treg research and therapy
The study of regulatory T cell (Treg) biology is major area of biomedicine. Treg therapies hold promise for treatment of many autoimmune diseases. Nonetheless, meaningful assays for studying Treg function in vitro are lacking. As one example, the commercially available "Treg inspector kit" is widely used yet relies on antibody-mediated engagement of CD28. This process cannot be regulated by CTLA4-mediated control of ligand expression, meaning that arguably the most significant mechanism of Treg function is therefore not "inspected". By developing a refined understanding of how CTLA4 interacts functionally with its two ligands, our work has the ability to impact on research practice and assay development in a very significant area of therapeutic immunology.
Training and career development
This work will support the career development of two postdoctoral scientists. The collaborative aspects of the programme will offer them opportunities to enhance their skill sets as well as disseminate understanding from our work. The proposed work is highly translational and will leave these individuals well-placed for careers in academia, the health sector or in the pharmaceutical industry.
Benefits to industry
The ability to modulate the immune system in a predictable way is a major goal of the pharmaceutical industry. The molecules which are the focus of this research programme (CD28, CTLA4, CD80, CD86) are widely recognized to play pivotal roles in the initiation and suppression of immune responses and as such have attracted considerable interest from pharmaceutical companies. Drugs to enhance the immune response can be used to fight cancer while drugs that suppress immunity can be used to treat autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis. However, effective use of these drugs depends on an accurate understanding of the biological function of each of these molecules. The results from this research are therefore likely to be of high value to the pharmaceutical industry and may lead to new drugs to target the CD28/CTLA4 pathway or to existing ones being used in different ways and in novel combinations.
Benefits to patients
A better understanding of how to control the immune system through the CD28/CTLA4 pathway promises to offer significant benefits for patient groups, particularly those with autoimmunity. Our recent work has shown that CTLA4 mutations in humans are associated with defective regulatory T cell function and an autoimmune syndrome (Nature Medicine, 2014) providing direct evidence of the critical importance of this pathway in humans. This prompts consideration of new therapeutic approaches in these patients and has already informed clinical decision making for some of these individuals. Further understanding of how this pathway works will therefore improve our ability to regulate autoimmunity. Given that the CD28/CTLA4 pathway is a major control point for immunity, relevant to a wide range of diseases, our research has the potential to bring health benefits to a large number of individuals.
Impact on Treg research and therapy
The study of regulatory T cell (Treg) biology is major area of biomedicine. Treg therapies hold promise for treatment of many autoimmune diseases. Nonetheless, meaningful assays for studying Treg function in vitro are lacking. As one example, the commercially available "Treg inspector kit" is widely used yet relies on antibody-mediated engagement of CD28. This process cannot be regulated by CTLA4-mediated control of ligand expression, meaning that arguably the most significant mechanism of Treg function is therefore not "inspected". By developing a refined understanding of how CTLA4 interacts functionally with its two ligands, our work has the ability to impact on research practice and assay development in a very significant area of therapeutic immunology.
Training and career development
This work will support the career development of two postdoctoral scientists. The collaborative aspects of the programme will offer them opportunities to enhance their skill sets as well as disseminate understanding from our work. The proposed work is highly translational and will leave these individuals well-placed for careers in academia, the health sector or in the pharmaceutical industry.
People |
ORCID iD |
Lucy Walker (Principal Investigator) | |
David Sansom (Co-Investigator) |
Publications
Edner N
(2020)
Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes
in Nature Immunology
Edner N
(2020)
Targeting co-stimulatory molecules in autoimmune disease
in Nature Reviews Drug Discovery
Edner NM
(2021)
Predicting clinical response to costimulation blockade in autoimmunity.
in Immunotherapy advances
Edner NM
(2021)
Publisher Correction: Targeting co-stimulatory molecules in autoimmune disease.
in Nature reviews. Drug discovery
Edner NM
(2023)
Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.
in Immunotherapy advances
Fox T
(2022)
Therapeutic gene editing of T cells to correct CTLA-4 insufficiency
in Science Translational Medicine
Halliday N
(2020)
CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4.
in Frontiers in immunology
Herold K
(2024)
The immunology of type 1 diabetes
in Nature Reviews Immunology
Heuts F
(2017)
Follicular T Helper Cells: A New Marker of Type 1 Diabetes Risk?
in Diabetes
Hou TZ
(2018)
Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity.
in Clinical immunology (Orlando, Fla.)
Description | Checkpoint control of T cell-B cell collaboration in the regulation of autoimmunity |
Amount | £1,900,785 (GBP) |
Funding ID | 220772/Z/20/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2021 |
End | 02/2026 |
Description | ENLIGHT-TENplus |
Amount | € 4,067,526 (EUR) |
Funding ID | 955321 |
Organisation | Marie Sklodowska-Curie Actions |
Sector | Charity/Non Profit |
Country | Global |
Start | 03/2021 |
End | 02/2025 |
Description | Exploring combination therapy to optimize costimulation blockade in autoimmunity |
Amount | £299,873 (GBP) |
Funding ID | 20/0006172 |
Organisation | Diabetes UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2021 |
End | 01/2024 |
Description | Identifying autoimmune signatures in patients receiving checkpoint immunotherapy |
Amount | £277,354 (GBP) |
Funding ID | C58264/A26593 |
Organisation | Cancer Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2019 |
End | 02/2022 |
Description | MSD Investigator Studies Program Review Committee (MISP-RC) |
Amount | £187,683 (GBP) |
Organisation | Merck |
Sector | Private |
Country | Germany |
Start | 06/2016 |
End | 07/2018 |
Description | Restoring Immune Regulation in Type 1 Diabetes |
Amount | £90,000 (GBP) |
Funding ID | A1992 |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2018 |
End | 05/2021 |
Description | Targeting follicular helper T cells across multiple autoimmune diseases |
Amount | £99,439 (GBP) |
Funding ID | 22931 |
Organisation | Versus Arthritis |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2022 |
End | 08/2023 |
Description | The role of type 2 innate lymphoid cells in autoimmune islet infiltration and diabetes |
Amount | £568,542 (GBP) |
Funding ID | MR/S009140/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2019 |
End | 08/2023 |
Description | Understanding the CD28-CTLA-4 pathway: a thermostat for T cell immunity |
Amount | £3,587,180 (GBP) |
Funding ID | 227384/Z/23/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 12/2023 |
End | 11/2031 |
Description | Collaboration with clinical oncologist |
Organisation | Royal Free London NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | This is a new collaboration between my research group and a clinical oncologist in the Royal Free Hospital. Our contribution to the partnership is to provide expertise in the area of immune regulation. Update: since the original collaborator left the Royal Free at the end of 2019, I have now formed a new collaborative link with 2 other individuals to continue the work. |
Collaborator Contribution | The partner's contribution is to provide clinical samples from cancer patients undergoing treatments that regulate the immune system. |
Impact | This collaboration is further supporting the objectives of my MRC funded programme and has also resulted in additional external funding. |
Start Year | 2016 |
Description | 275th Anniversary Symposium of Friedrich-Alexander University Erlangen |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | I was a Plenary Speaker at the 275th anniversary symposium of Friedrich-Alexander University Erlangen, Germany (18-19th January 2018). The topic was "Future Challenges in Medicine" and the presentation was to a mixed audience of general public, scientists, clinicians...etc. |
Year(s) Of Engagement Activity | 2018 |
Description | Diabetes UK Funders Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | Presentation on our diabetes research at Diabetes UK Funders meeting 27th July 2017. |
Year(s) Of Engagement Activity | 2017 |
Description | Diabetes UK Lab Tour |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Supporters |
Results and Impact | Around 20 Diabetes UK supporters attended an evening lab tour to experience a research lab first hand. The evening started with a brief talk about what we do, followed by the participants circulating around 3 bases to experience different aspects of lab work. At each base, a member of my research team introduced a particular technique and allowed people to try some hands on practical work. There were lots of questions throughout the evening. |
Year(s) Of Engagement Activity | 2018 |
Description | Global Immunotalk - online international presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I spoke in the Global Immunotalks series, an international seminar series for leading immunologists established during the COVID19 pandemic. My talk is available online and has been viewed 2.6 thousand times. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=Kq7rM1jHJ9Q |
Description | Hosted Type 1 Diabetes Immunotherapy Consortium meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I hosted the Type 1 Diabetes Immunotherapy Consortium meeting at the Pears Building. Clinicians and scientists came together from across the UK to discuss the latest research developments. The consortium, funded by Diabetes UK and JDRF, comprises a network of UK-based research sites, including the Royal Free Hospital. Its aim is to promote, develop and support immunotherapy research in type 1 diabetes. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.royalfree.nhs.uk/news-media/news/developing-a-deeper-understanding-of-type-1-diabetes/ |
Description | Imperial Immunology Short Course |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | I gave a Special Guest Lecture at Imperial Immunology Short Course on 20th November 2017. The talk focused on understanding how the immune system is naturally regulated and why these regulatory mechanisms sometimes go wrong. |
Year(s) Of Engagement Activity | 2017 |
Description | Interview for Newspaper article |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | I was interviewed for a newspaper article (for the i) about my research findings on T cell profiles in people with type 1 diabetes responding to immunotherapy. I was contacted by a dozen or so people afterwards requesting additional information and I liaised with these individuals by email. |
Year(s) Of Engagement Activity | 2020 |
Description | Invited Expert - JDRF philanthropy event for high level donors |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | A reception was held on 15 June 2022 at the Oxford and Cambridge club for around twelve of JDRF's highest level philanthropists. I discussed our diabetes research with these individuals in an informal small group setting. I later hosted a lab visit for a relative of one of the individuals present. |
Year(s) Of Engagement Activity | 2022 |
Description | Invited Seminar, University of Cambridge |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar to present recent data for discussion. |
Year(s) Of Engagement Activity | 2021 |
Description | Invited Speaker - "The promise of IL-2 therapy" Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I participated as Invited Speaker at a meeting focused on The promise of IL-2 therapy for autoimmune and inflammatory disorders, transplantation and cancer. The meeting was held in Paris in September 2022. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.il-2-2022.com |
Description | Invited Speaker - Aegean Conference on Autoimmunity |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Speaker - Aegean Conference on Autoimmunity, Oct 2022 |
Year(s) Of Engagement Activity | 2022 |
Description | Invited Speaker - Av Mitchison Memorial meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker at a symposium to honour the late great immunologist Av Mitchison. "Ideas in contemporary immunology : a meeting in memory of Av Mitchison" 11 Sept 2023 at University College London |
Year(s) Of Engagement Activity | 2023 |
Description | Invited Speaker - Francis Crick Institute Research Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar for the Francis Crick Institute Immunology Interest Group |
Year(s) Of Engagement Activity | 2023 |
Description | Invited Speaker - Francis Crick Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Speaker at the London Infections & Immunity Symposium at the Francis Crick Institute, Oct 2022 |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.crick.ac.uk/whats-on/the-london-infections-immunity-symposium-2022 |
Description | Invited Speaker - Helmholtz Immunology Distinguished Speaker Series |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk for the Helmholtz Immunology Distinguished Speaker Series, May 2023 |
Year(s) Of Engagement Activity | 2023 |
Description | Invited Speaker - Immunotherapy symposium in Regensburg |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I spoke as invited speaker at an Immunotherapy Symposium in Regensburg, 29 June 2022 |
Year(s) Of Engagement Activity | 2022 |
Description | Invited Speaker - Japanese Society for Immunology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Speaker - Japanese Society for Immunology, Chiba Jan 2024 |
Year(s) Of Engagement Activity | 2024 |
Description | Invited Speaker - Keystone Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker - Keystone symposium on T cell B cell Collaboration in Germinal Centers and Beyond, Whistler Oct 2023 |
Year(s) Of Engagement Activity | 2023 |
Description | Invited Speaker - Scandinavian Society for Immunology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker Scandinavian Society for Immunology, June 2023 |
Year(s) Of Engagement Activity | 2023 |
Description | Invited Speaker - University of Freiburg |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar, University of Freiburg |
Year(s) Of Engagement Activity | 2022 |
Description | Invited Speaker - University of Tokyo |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Speaker at the Tokyo University, Jan 2024 |
Year(s) Of Engagement Activity | 2024 |
Description | Invited Speaker, American Association of Diabetes |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation at the American Association of Diabetes annual congress |
Year(s) Of Engagement Activity | 2021 |
Description | Invited Speaker, Chernajovsky Biomedical Research Foundation meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This initiative will bring together major research funders, industry and academics to harness the collective knowledge in the immunology field to develop therapeutics targeted at common fundamental pathological processes in autoimmune diseases. To kick start this initiative we are convening a 1 day expert meeting to be held (via Zoom) in May this year. The aim of this meeting will be to identify a new, innovative set of research priorities that help break down disease-specific research silo's. As a leading researcher in the field I would like to invite you as one of the plenary speakers to present on immune tolerance. |
Year(s) Of Engagement Activity | 2021 |
Description | Invited Speaker, University of Queensland, 2021 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Seminar to share recent data and discuss collaboration. |
Year(s) Of Engagement Activity | 2021 |
Description | Keynote Speaker - Austrian Society for Immunology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Keynote Speaker at the Austrian Society for Immunology, Linz, Sept 2023 |
Year(s) Of Engagement Activity | 2023 |
Description | Launch of Connect Immune Research at Houses of Parliament |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Invited to Parliamentary Event hosted by Philip Dunne MP for the launch of Connect Immune Research. This is a collaboration between JDRF, Versus Arthritis and the MS Society to support research into autoimmune diseases. |
Year(s) Of Engagement Activity | 2018 |
Description | Pears Building Neighbourhood Event |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Pears Building Neighbourhood Event, 6th July 2023. Lay presentations of research to the public, including interview with type 1 diabetes patient. |
Year(s) Of Engagement Activity | 2023 |
Description | Podcast for SugarScience |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Podcast to discuss recent research findings for the(sugar)science. This is an interactive digital platform helping scientists who study type 1 diabetes to connect, collaborate and gain funding for their best ideas. |
Year(s) Of Engagement Activity | 2020 |
Description | Presentation to JDRF Biomarker working group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk to share recent findings with the JDRF biomarker working group. Discussion of new biomarkers that may be relevant in people with Type 1 Diabetes receiving new immunotherapies. |
Year(s) Of Engagement Activity | 2021 |
Description | Public Event on "Developing a deeper understanding of type 1 diabetes" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | I organised and spoke at a diabetes event for the Royal Free Hospital "Medicine for Members" series on "Developing a deeper understanding of type 1 diabetes". This event showcased the joint work of the diabetes specialist clinical teams and researchers to help develop a better understanding of the changes within the body that accompany the disease. We also shared details about a new national screening programme for children who may be at risk of developing type 1 diabetes in the future. The event was held online with an audience Q&A session and the recording is publicly available on youtube. Example of online feedback received: "Excellent and truly inspirational Medicine for Members. Well done to all who participated and organised this presentation". |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.youtube.com/watch?v=twH_HVg9N2A |
Description | Public Event to mark World Immunology Day 2022 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | To celebrate World Immunology Day 2022, I spoke at the hybrid online/in-person public event organised by the Crick, Nature journals and British Society for Immunology. There was an international audience of more than 300 online attendees as well as those in the room. The event was held at the Crick on 28th April 2022 and involved an opening presentation from me and then a panel discussion chaired by award-winning broadcaster Claudia Hammond. The event was filmed and the in-person and online audiences contributed to the questions/discussion. The recording is publicly available on youtube. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.crick.ac.uk/whats-on/world-immunology-day-autoimmunity-when-your-immune-system-turns-on-... |
Description | Radio 4 Woman's Hour interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | I gave an interview on the Connect Immune Research initiative which brings together multiple funders to investigate cross-disciplinary working in autoimmune diseases. |
Year(s) Of Engagement Activity | 2021 |
URL | https://twitter.com/JDRFUK/status/1402588618846310403 |
Description | Seminar, Kennedy Institute Oxford |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Seminar to share recent data for discussion. |
Year(s) Of Engagement Activity | 2021 |
Description | State of the Science debate on type 1 diabetes |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Debate organised by theSugarScience, 13th Jan 2022, on the variability of type 1 diabetes - is it one disease or endotypal? How does this impact the development of treatments? I was part of a panel of international experts to debate these questions. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=P4nrVrb2AhU&t=1s |
Description | Talk at IIT Schools Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Hosting a visit for local school children at the UCL Institute of Immunity and Transplantation on 27th June 2017. Running a stand with activities, explaining and discussing our research. |
Year(s) Of Engagement Activity | 2017 |
Description | Talk at JDRF Discovery Day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Dr Frank Heuts from my group presented our research at a JDRF event for families affected by type 1 diabetes on 3rd June 2017. These events bring together families to share experience and knowledge, and to hear about the latest developments in diabetes research. |
Year(s) Of Engagement Activity | 2017 |
Description | Talk at local diabetes support group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | A member of my team gave a presentation at a Barnet Diabetes Support Group meeting in October 2022 |
Year(s) Of Engagement Activity | 2022 |
Description | Tumour Immunology Course |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I gave a lecture on CD28 and CTLA-4 at a Tumour Immunology course in Tartu Estonia (23rd-25th August 2017). |
Year(s) Of Engagement Activity | 2017 |
Description | Visit of Her Majesty the Queen |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Visit of HRH The Queen to UCL diabetes research labs organised by JDRF and Connect Immune Research. Tour of Walker Lab to learn about our type 1 diabetes research. Following the research tour, The Queen joined a reception where she met JDRF supporters including Theresa May MP, Derrick Evans (Mr Motivator), Sheku Kanneh-Mason MBE, and Nina Wadia who spoke about their first-hand experience of living with type 1 diabetes and their hopes for the future of research. Sir Trevor Pears also attended. Prof Walker gave a brief research presentation and took part in a "Chat Show" style Q&A. |
Year(s) Of Engagement Activity | 2023 |
Description | Visit of Professor Dr HRH Princess Chulabhorn Princess of Thailand |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Policymakers/politicians |
Results and Impact | Visit of Professor Dr HRH Princess Chulabhorn Princess of Thailand and President of the Chulabhorn Research Institute. (Research presentation & reception) |
Year(s) Of Engagement Activity | 2023 |