King's College London – Confidence in Concept 2019
Lead Research Organisation:
King's College London
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
The Confidence in Concept (CIC) scheme is a key part of MRC’s translational research strategy and provides annual awards to institutions to flexibly support a portfolio of early stage translational research projects. CIC is designed to accelerate the transition from discovery research to viable translational projects by supporting preliminary studies to establish proof-of-concept so that the approach will then become competitive for more substantial translational funding.
People |
ORCID iD |
Publications
Safinia N
(2021)
Advances in Liver Transplantation: where are we in the pursuit of transplantation tolerance?
in European journal of immunology
Egerton A
(2023)
Anterior cingulate glutamate metabolites as a predictor of antipsychotic response in first episode psychosis: data from the STRATA collaboration.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Hudecek J
(2020)
Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials.
in NPJ breast cancer
Li M
(2023)
B Cells in Breast Cancer Pathology
in Cancers
Cheung A
(2022)
CDK Inhibition Primes for Anti-PD-L1 Treatment in Triple-Negative Breast Cancer Models
in Cancers
Kurt AS
(2022)
IL-2 availability regulates the tissue specific phenotype of murine intra-hepatic Tregs.
in Frontiers in immunology
Alberts E
(2021)
Immune Crosstalk Between Lymph Nodes and Breast Carcinomas, With a Focus on B Cells.
in Frontiers in molecular biosciences
Griffiths K
(2022)
Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study.
in Schizophrenia (Heidelberg, Germany)
Williams S
(2022)
Interpolation of electrophysiology parameters using OpenEP: technology development and clinical application
in EP Europace
Beck K
(2022)
N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study
in European Psychiatry
Williams SE
(2021)
OpenEP: A Cross-Platform Electroanatomic Mapping Data Format and Analysis Platform for Electrophysiology Research.
in Frontiers in physiology
Quist J
(2021)
Random Forest Modelling of High-Dimensional Mixed-Type Data for Breast Cancer Classification.
in Cancers
Brito B
(2023)
Redox double-switch cancer theranostics through Pt( iv ) functionalised manganese dioxide nanostructures
in Nanoscale
Muliaditan T
(2021)
Synergistic T cell signaling by 41BB and CD28 is optimally achieved by membrane proximal positioning within parallel chimeric antigen receptors.
in Cell reports. Medicine
Beatson RE
(2021)
TGF-ß1 potentiates V?9Vd2 T cell adoptive immunotherapy of cancer.
in Cell reports. Medicine
Winstone H
(2021)
The Polybasic Cleavage Site in SARS-CoV-2 Spike Modulates Viral Sensitivity to Type I Interferon and IFITM2.
in Journal of virology
Rogeau A
(2022)
The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study.
in Molecular psychiatry
El Bairi K
(2021)
The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.
in NPJ breast cancer
Harris RJ
(2021)
Tumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes in Triple-Negative Breast Cancer.
in Cancer research
Sivakumar M
(2022)
Widespread gaps in the quality of care for primary biliary cholangitis in UK.
in Frontline gastroenterology
| Description | Engage pathologists in research |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Description | 5763189 - City of London CRUK Studentship Award |
| Amount | £149,549 (GBP) |
| Funding ID | WT- 5763189 |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2021 |
| End | 09/2025 |
| Description | Engineering regulatory T cells (Tregs) to modulate kidney injury and prevent renal fibrosis |
| Amount | £186,808 (GBP) |
| Organisation | Kidney Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2022 |
| End | 05/2024 |
| Description | Infection and Immunity Board |
| Amount | £792,755 (GBP) |
| Funding ID | MR/W025221/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2022 |
| End | 05/2025 |
| Description | Inorganic nanoparticles for radiolabelling with 223Ra / 212Pb, for multimodal imaging and therapy in cancer. EPSRC -SMART IMAGING CDT/NNL |
| Amount | £115,000 (GBP) |
| Organisation | King's College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 08/2026 |
| Description | Optimization of the potency, specificity and survival properties of engineered regulatory T cells to treat inflammatory liver diseases |
| Amount | £198,505 (GBP) |
| Organisation | Rosetrees Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 11/2024 |
| Description | The mechanistic basis for the ZAP antiviral system targeting viral and cellular RNAs |
| Amount | £943,911 (GBP) |
| Funding ID | MR/W018519/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 03/2025 |
| Title | AI-based methodologies to capture immune responses in lymph nodes |
| Description | We have implemented a deep learning framework to capture and quantify immune responses in lymph nodes. Some of these immune responses in lymph nodes are informative of the risk of developing distant metastasis in triple negative breast cancers. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | If test in larger cohort, the deep learning methods can be included in a digital pathology approach in our clinics. |
| Title | Optimization of a 8-colour phosphoflow cytometry panel to identify and measure NF-kBp65 phosphorylation in blood cDC2 |
| Description | We have optimized a 8-colour phospho flow cytometry panel to measure NF-kBp65 phosphorylation in blood cDC2, streamlining out discovery assay previously established as biomarker assay to predict clinical response to the anti-TNF biologic drug adalimumab in psoriasis. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2022 |
| Provided To Others? | No |
| Impact | It simplifies the previous assay making it possible to run it on clincial grade flow cytometers |
| Title | Lymph node immune response detection |
| Description | We have collected a large cohort of lymph nodes from breast cancer patients across different hospitals. In addition, we have implemented a deep learning framework to capture diverse immune responses in lymph nodes. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2022 |
| Provided To Others? | No |
| Impact | We are currently submitting our research for publication and will then make our dataset publicly available. |
| Description | Exploring morphological immune responses in lymph nodes and tertiary lymphoid structure of breast cancer patients |
| Organisation | Boehringer Ingelheim |
| Country | Germany |
| Sector | Private |
| PI Contribution | My group has recently identified that immune responses in cancer-free and involved lymph nodes of breast cancer patients is indicative of disease progression, especially for high risk triple negative breast cancer with low levels of tumour immune infiltrates. In the confidence in concept 2019 grant, we can test these findings in neoadjuvantly treated triple negative breast cancer patients. We are exploring the spatial and cellular composition of cancer-free and involved lymph nodes in triple negative breast cancer patients, by spatial transcriptomics using the nanoString GeoMx DSP, multiplex immuno flurescence and CyTOF. |
| Collaborator Contribution | Dr Dinis Calado and his group at the Francis Crick has helped us to set up mouse models of triple negative breast cancers. Since Dr Calado is an expert in germinal center formation, he is directly advising us on the functional studies of lymph nodes, tumours and immune infiltrates at the primary tumour site. |
| Impact | PhD studentship from the CRUK City of London Major Center Opn2Expert collaboration with Boehringer Ingelheim MRC infection and immunity project grant This is a multidisciplinary collaboration -I am computer scientist and Dinis Calado is an expert in mouse models. For these above listed grants, we also work with Sarah Pinder, consultant pathologists (GSTT, KCL); with Simon Walker Samuel (UCL) on High-resolution Episcopic Microscopy; with Alan Ramsay (KCL) on ex vivo cultures; and Pascal Meier (ICR) how cell death influences immune reactions. |
| Start Year | 2020 |
| Description | Feasibility Study of an adapted app based anxiety intervention for autistic people |
| Organisation | Autistica |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | The anxiety app is co-owned by Autistica and King's College London. The product owner of the app (based at Autistica) supports the research team at King's College London to incorporate app content that they have designed, which is technically implemented by EqualEyes (the app developers). |
| Collaborator Contribution | App and app content development and implementation. Co-author of publication on study protocol (in submission). Developing the app for ORCHA approval. |
| Impact | Molehill Mountain app (https://www.autistica.org.uk/molehill-mountain). Publication on study protocol (in submission PLOS ONE). |
| Start Year | 2020 |
| Description | Inorganic nanoparticles for radiolabelling with 223Ra / 212Pb, for multimodal imaging and therapy in cancer. |
| Organisation | National Nuclear Laboratory |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We are developing radiotherapy nanoparticles (Quantum dots) |
| Collaborator Contribution | NNL have sponsored a PhD student in my research group under the topic above, this started in September 2022. |
| Impact | none so far. |
| Start Year | 2022 |
| Description | Investigating effect of radiation therapy combined with anti-LIF mAb on the tumour immune microenvironment |
| Organisation | AstraZeneca |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We are optimising radiotherapy/LIF protocols in cancer/immune cell cocultures |
| Collaborator Contribution | AstraZeneca have contributed the anti LIF mab |
| Impact | N/A |
| Start Year | 2022 |
| Title | HO-1 targeting immunotherapeutics |
| Description | The patent covers the manufacture and use of a novel inhibitor of Heme oxygenase-1. The inhibitor has superior anti-tumour efficacy and bioavailability as validated using preclinical models of cancer. We have also developed and validated a novel synthetic manufacture pipeline for the large scale production of the compound. |
| IP Reference | |
| Protection | Patent / Patent application |
| Year Protection Granted | 2023 |
| Licensed | No |
| Impact | None to report yet |
| Title | 3D Fetal Brain MRI reconstruction AIDE app |
| Description | AIDE is an open-source platform for the deployment of AI applications in healthcare settings. This software packages automated 3D Fetal Brain MRI reconstruction into a MONAI Application Package (MAP) for execution on AIDE. |
| Type Of Technology | Software |
| Year Produced | 2022 |
| Impact | Just released. Integration of 3D fetal brain MRI to AIDE makes it accessible cat King's College Hospital NHS Foundation Trust, to support NHS clinicians to help improve direct patient care. |
| URL | https://github.com/SVRTK/aide-svrtk |
| Title | Molehill Mountain |
| Description | An app-based tool for anxiety management specifically adapted for autistic people. |
| Type Of Technology | Webtool/Application |
| Year Produced | 2021 |
| Open Source License? | Yes |
| Impact | The app has been downloaded by well over 15,000 people. We are now implementing the app in a clinically derived population of autistic people for the first time. The app is currently under further development for a clinical trial design (specifically, through the development of a diary control app alongside the main active app version). |
| Title | Radiopharmaceutical dispenser |
| Description | The commercial dispenser currently operated within PERL has a number of weaknesses: overly complex control software, reliability issues, cost, and slow overall processing time (which is too long for dispensing radiopharmaceuticals labelled with short-lived radionuclides). An in-house constructed radiopharmaceutical dispenser, suitable for dispensing 64CuGTSM, was proposed: the design focus was towards developing a GMP grade dispenser that can be installed into an R&D lab environment. This approach enables the capability to develop a 64Cu-labelled GTSM dispensing process within an R&D lab prior to technology transfer into GMP manufacturing. A prototype system was developed, capable of rapid dispensing of a 5 mL volume into 2 vials with a dispensed volume accuracy +/-1% - testing was successfully completed. The 64CuGTSM dispenser is now under construction, which will be capable of dispensing a 10 mL volume into 4 vials. These platforms have been constructed using 3D printed hardware and low-cost components for automation. |
| Type Of Technology | Systems, Materials & Instrumental Engineering |
| Year Produced | 2022 |
| Impact | The development of this dispensing product will overcome a number of weaknesses associated with the current dispenser used, and allow the translation of 64CuGTSM from R&D phase to GMP, via direct technology transfer. |
| Description | EMBO workshop on codon usage |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I presented a talk at the EMBO workshop on codon usage entitled 'Inhibition of HIV-1 replication by ZAP-response elements in the viral RNA genome'. In addition, a postdoc in the lab presented a poster on synonymous genome recoding of the influenza A virus. These presentations to discussion and new ideas. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://meetings.embo.org/event/21-codon |
| Description | Microbiology Society Annual Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | In 2017, I gave a talk at the Microbiology Society Annual Conference entitled "Regulation of human immunodeficiency virus type 1 (HIV-1) Gag expression and virion production by SR proteins". In addition, a PhD student in my lab, gave a talk on "Altering the CG content of the HIV-1 gag sequence attenuates viral replication". Finally, a PhD student in a lab that I am collaborating with on how HIV-1 RNA sequences regulate its replication gave an talk on "Cis-acting RNA sequences regulate HIV-1 envelope and Vpu translation". In 2022, I gave a talk at the Microbiology Society Annual Conference entitled "Inhibition of viral gene expression and replication by ZAP, TRIM25 and KHNYN". In addition, a postdoc in my lab presented a poster on synonymous genome recoding of Influenza A virus. |
| Year(s) Of Engagement Activity | 2017,2022 |
| Description | Molehill Mountain Stakeholder Advisory Group |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | We have engaged in several stakeholder engagement activities over the course of the project, and are in frequent ongoing contact with our stakeholder group (e.g., via email, Slack), resulting in meaningful outcomes in terms of the project progress. Our stakeholder engagement activities to date have included: 1) A kick-off meeting to discuss the study and gather overall feedback from the group; 2) Co-designing an outcome measure to assess change in anxiety related functional outcomes (the GAS), now being administered to all participants in the study; 3) Selection of optimal autistic trait measures, now being administered to all participants in the study; 4) Co-designing endpoint surveys and interview questions; 5) Feedback on our statistical analysis plan; 6) A preliminary discussion regarding future clinical trial designs in this area (planned for March 2023). In future, we have further plans for, sharing quantitative and qualitative data analyses with the group for discussion and feedback (also on interpretation of findings); and facilitating contributions to the final write up and dissemination of main study results. |
| Year(s) Of Engagement Activity | 2022,2023 |
| Description | Presentation at British Nuclear Medicine Society |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a presentation given at the BNMS meeting to an audience of nuclear medicine professionals including nuclear medicine/PET consultants and doctors, clinical scientists, physicists, technicians, radiographers, technologists, nuclear medicine industry, academics, and radiochemists. The purpose of the presentation was to inform and engage the Nuclear Medicine community about the potential of metal radionuclides in nuclear medicine, and specifically the 64CuGTSM tracer (and others) which can deliver metal radionuclides across the blood brain barrier; likely clinical applications include imaging of Wilson's Disease, Alzheimer's Disease and other neurological diseases. Feedback from delegates rated the talk 4.50 (weighted average; scale 1= poor and 5 = excellent); average score for all talks was 4.20. Several discussions followed about the use of metal radionuclides in nuclear medicine. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.bnms.org.uk/mpage/Autumn2022homepage |
| Description | Presentation at UKRG |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a presentation given at the UK Radiopharmacy Group meeting to an audience of nuclear medicine professionals including radiopharmacists, radiopharmaceutical scientists, nuclear medicine industry, technicians, and physicists. The purpose of the presentation was to inform and engage the Nuclear Medicine community about the potential of metal radionuclides in nuclear medicine, and specifically the 64CuGTSM tracer (and others) which can deliver metal radionuclides across the blood brain barrier; likely clinical applications include imaging of Wilson's Disease, Alzheimer's Disease and other neurological diseases. Several discussions followed about the use of metal radionuclides in nuclear medicine. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Press interviews |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Media interviews leading to published articles eg in The Guardian |
| Year(s) Of Engagement Activity | 2022,2023 |
| Description | Provide information to a student panel on science |
| 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 | Discussed with a student doing a science engagement course who wrote an internet piece and youtube video |
| Year(s) Of Engagement Activity | 2022 |
| Description | Technical Workshop - PET radiopharmaceuticals dispensing and validation |
| 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 | Attended PET workshops about dispensers and validation and discussed the potential for making our in-house dispenser, and methods for validation of new products, using the approach followed internally in PERL. The information we shared was useful to other attendees as our approach is more comprehensive than their methods. This was a meeting of people working in PET radiochemistry providing clinical PET radiopharmaceuticals for patients. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Zooniverse project |
| 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 | Public/other audiences |
| Results and Impact | We created a zooniverse project in which we ask the general public to help us annotate lymph nodes https://www.zooniverse.org/projects/effeli/node-code-breakers-looking-for-patterns-in-lymph-nodes? |
| Year(s) Of Engagement Activity | 2021,2022 |
| URL | https://www.zooniverse.org/projects/effeli/node-code-breakers-looking-for-patterns-in-lymph-nodes |