DPFS Devolved Portfolio (Pilot).
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
This is an award of a devolved portfolio under a pilot phase, as part of the implementation of the Development Pathway Funding Scheme (DPFS). DPFS Devolved Portfolios are block awards for specific universities to support goal-orientated translational research projects. The award allows universities to allocate the money to different translational projects more responsively based on their relative progress. For example the university might decide to stop a particular project and recycle the money allocated to it into other proposals. All projects supported by the Portfolio fall within the remit of the Development Pathway Funding Scheme (DPFS).
Organisations
People |
ORCID iD |
Publications
Reeder C
(2010)
Different components of metacognition and their relationship to psychotic-like experiences.
in Behavioural and cognitive psychotherapy
Holdom MD
(2011)
Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor Fc?RI.
in Nature structural & molecular biology
| Description | Circuits |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Description | DPFS |
| Amount | £172,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2010 |
| End | 08/2012 |
| Title | Arterial smooth muscle cell lines |
| Description | Immortalized versions of pulmonary arterial smooth muscle cells derived from control subject and a pulmonary arterial hypertension patient. |
| Type Of Material | Cell line |
| Provided To Others? | No |
| Impact | Cell lines suitable for downstream research |
| Title | Arterial stiffness database |
| Description | The database comprises measures of isobaric arterial stiffness in relation to patient characteristics such as 24 hour ambulatory blood pressure and target organ damage. It will be used to assess the discriminatory value of isobaric arterial stiffness with respect to hypertension severity as assessed by target organ damage. |
| Type Of Material | Biological samples |
| Provided To Others? | No |
| Impact | N/A |
| Title | Coincidence detection |
| Description | This is a DNA capture method reliant on two-component proximity to enable sensitive detection of proteins. |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | nA |
| Title | Neuroimaging biomarkers |
| Description | MRI data |
| Type Of Material | Biological samples |
| Provided To Others? | No |
| Impact | NA |
| Title | V12RAS-zebrafish transgenic cell line: Model of mechanisms or symptoms - non-mammalian in vivo |
| Description | We have now established a breeding stock at KCL of this transgenic fish which has RAS driven tumour formation in the larval stage |
| Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
| Provided To Others? | No |
| Impact | NA |
| Title | joystick runway task |
| Description | The defensive model of anxiety can be used to explain behavior in a wide range of settings |
| Type Of Material | Model of mechanisms or symptoms - human |
| Year Produced | 2011 |
| Provided To Others? | Yes |
| Impact | Three TV programmes and a section in the popular science book The Psychopath Test by Jon Ronson. Also my work is cited highly enough to give me an H index of 7, ahead of what would be expected for a PhD graduate from 2009. |
| Title | AORTIC PULSE WAVE VELOCITY MEASUREMENT |
| Description | Embodiments of the present invention provide a measurement protocol that is able to non- invasively provide a degree of characterisation of aortic stiffness, at least qualitatively. The measurement protocol includes varying intra-thoracic pressure via a series of respiratory manoeuvres, whilst collecting aortic blood flow velocity information using a suitable scanning technique, and from which pulse wave velocity (PWV) may then be found. Plotting PWV against aortic trans-mural pressure variations caused by the changes in intra-thoracic pressure should allow a degree or aortic stiffness characterisation to be performed, in that a diseased aorta should show less variation in PWV with changes in trans-mural pressure than a healthy aorta. Also developed as another embodiment is a magnetic resonance (MR) technique for measuring aortic pulse wave velocity, which is able to achieve high temporal resolution on pulse velocity data capture, and hence lead to accurate PWV calculation. The technique uses a time sliding subtraction of velocity projections obtained from bipolar phase encoding gradients to produce velocity profiles at least every second repetition time TR, and in some variants every TR. |
| IP Reference | WO2013110929 |
| Protection | Patent application published |
| Year Protection Granted | 2013 |
| Licensed | No |
| Impact | N/A |
| Title | CIRCuiTS - Computerised Remediation of Cognition - Training for Schizophrenia |
| Description | This is novel computerized psychological therapy for people with a diagnosis of schizophrenia which aims to improve thinking skills such as attention, memory and problem-solving. |
| IP Reference | |
| Protection | Copyrighted (e.g. software) |
| Year Protection Granted | 2011 |
| Licensed | Yes |
| Impact | Currently being used in a number of RCTs of CRT across the world (see above). |
| Title | COINCIDENCE DETECTION |
| Description | The invention relates to a method of detecting the coincidence of two biomolecular structures in a solid phase sample, said method comprising: (i) providing a first and a second fusion protein, each fusion protein comprising (a) a detection domain, said detection domain comprising a DNA binding domain; said detection domain capable of binding a cognate specific nucleotide sequence in co-operation with a further detection domain; (b) a recognition domain, said recognition domain capable of binding a target biomolecular structure; and (c) a connector domain; said connector domain being fused at one end to the detection domain and being fused at the other end to the recognition domain; wherein at least two of (a), (b) and (c) are heterologous to one another; wherein the recognition domains of said first and said second fusion proteins are capable of binding to first and second biomolecular structures; (ii) contacting the sample with said first and second fusion proteins; (iii) incubating to allow binding; (iv) removing unbound fusion protein; (v) contacting the sample with nucleic acid comprising said cognate specific nucleotide sequence; (vi) incubating to allow heterotrimeric binding of the nucleic acid; (vii) detecting nucleic acid bound to the sample wherein detection of nucleic acid in step; (vii) indicates that the two biomolecular structures are present coincidentally in said sample. |
| IP Reference | WO2011161420 |
| Protection | Patent application published |
| Year Protection Granted | 2011 |
| Licensed | No |
| Impact | NA |
| Title | Circuits |
| Description | Computer software for Cognitive Remedial Therapy |
| IP Reference | |
| Protection | Copyrighted (e.g. software) |
| Year Protection Granted | 2011 |
| Licensed | No |
| Impact | Software is being evaluated in a RCT |
| Title | A Repeatable and Objective Behavioural Assay of Anxiety in Humans |
| Description | The Joystick Operated Runway Task is now being tested with anxiety patients with a view to being used to characterize treatment response. |
| Type | Support Tool - For Medical Intervention |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | We have proved the joystick task is sensitive to the established anti-anxiety drug lorazepam so the task can now be used to test new drugs for anti-anxiety properties |
| Title | Antithrombotic agent for the prevention of antibody mediated rejection in renal transplantation |
| Description | "This project seeks to establish the feasibility of using a novel class of antithrombotic agents - cytotopic thrombin inhibitors - in transplantation. The clinical target is antibody-mediated acute rejection (AMR). This can arise because potential recipients of grafts have pre-existing antibodies against blood group (ABO) or human leukocyte antigens in the donated organ. At least 15% of potential recipients are denied transplantation for this reason and some manifestation of AMR is estimated to occur in 10-15% of renal transplants. AMR involves activation of the classical pathway of the complement system but this system interacts with coagulation pathways so that complement activation and thrombotic consequences go hand in hand. Thrombosis treated with anticoagulants given systemically is associated with a bleeding risk which is generally unacceptable in transplant surgery. Building on a chemical strategy which has been applied successfully to modified complement regulatory molecules, we have prepared novel inhibitors of thrombin which can be anchored to the vascular surface in organs by perfusion prior to transplantation. This permits the graft rather than the recipient patient to be anticoagulated. We have used an animal model of AMR in which sensitised rats rapidly reject transplanted kidneys. Preliminary results with a locally perfused lead compound have suggested that graft survival can be prolonged under conditions that avoid a major risk of bleeding. We are seeking support to validate this conclusion and to investigate if combination with complement inhibitors provides added benefit. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | On hold |
| Impact | tbc |
| Title | Circuits |
| Description | We are currently undertaking early clinical assessment in a feasibility RCT (n=120) funded by a RfPB grant (see above). Also, being assessed in various other RCTs around the world. Current pilot feasibility data being collected using different methods of delivery (e.g. in groups). |
| Type | Therapeutic Intervention - Psychological/Behavioural |
| Current Stage Of Development | Refinement. Clinical |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | The program is currently being tested in a RCT. This CRT programme is unique in (a) having clear theoretical underpinnings; (b) being specifically designed for a schizophrenia patient group; (c) incorporating a metacognitive therapeutic stance; (d) incorporating a clear role for therapists; (e) being easily translatable and already translated into several languages. |
| Title | Computerised cognitive remediation therapy programme for schizophrenia |
| Description | "Cognitive Remediation Therapy (CRT) improves cognitive and social functioning in schizophrenia, but reliance on intensive therapist input limits its implementation within the NHS. Computerised CRT reduces therapist burden but existing packages have not been designed for schizophrenia. CIRCuiTS is a new, ecologically-valid, graphically and functionally sophisticated computerised CRT programme, driven by clear theoretical principles and relies on well-researched training techniques for schizophrenia. The software is complete, but its feasibility and acceptability, particularly in relation to its method of delivery and dose of treatment have not been assessed. This study will investigate: (a) the acceptability and feasibility of CIRCuiTS for a wide range of cognitive and computer abilities; (b) the extent to which patients need therapist assistance; (c) any therapist interface difficulties that might arise (d) the levels of within-therapy change that impact on outcome cognitive change to provide therapists with a within-therapy goal for task change. Feedback from this study will result in a refined therapeutic manual so that the programme will be ready to be tested in clinical trials. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Psychological/Behavioural |
| Current Stage Of Development | Refinement. Clinical |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | Still in development |
| URL | http://www.isrctn.com/ISRCTN55488371 |
| Title | Detection and characterisation of Clostridium difficile in diarrhoeal stools |
| Description | "This is academic/industry collaboration between KCL, Brandeis University and Smiths Detection. Clostridium difficile (CD) is a major cause of hospital/healthcare outbreaks of diarrhoea, associated with significant morbidity and mortality. CD causes disease by production of toxins A and B (encoded by genes tcdA, tcdB). Recent outbreaks have been due to virulent strains, most commonly ribotype 027, which produces an additional binary toxin (encoded by cdtA, cdtB) and hyperproduces toxin because of variation in the repressor gene tcdC. Rapid diagnosis is essential for patient management and infection control. Diagnosis is usually by Enzyme Immuno-Assay (EIA) of toxins A and B, but performance of present kits is unsatisfactory. Detection of glutamate dehydrogenase (GDH) is more specific but does not distinguish toxigenic from non-toxigenic strains. One commercial PCR system for detection of genes for B and binary toxins and one genetic variation in tcdC has been announced performance data are limited. There is a need for a rapid test to simultaneously detect genes for toxins A/B and binary, toxin hyperproduction and CD type. We propose to develop such a test using the Smiths Bioseeq automated LATE-PCR system, which allows complex multiplexing and can be run safely by non-specialised staff in non-laboratory settings. Most recent work supported by DPFS Portfolio Award" |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2011 |
| Development Status | Closed |
| Impact | tbc |
| Title | ESTABLISHING EARLY NEUROIMAGING BIOMARKERS TO PREDICT TREATMENT RESPONSE IN SCHIZOPHRENIA |
| Description | The findings of this study are pointing to the presence of neuroanatomical markers that could be used as early predictors of response to treatment and outcome. |
| Type | Diagnostic Tool - Imaging |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2012 |
| Development Status | Actively seeking support |
| Impact | NA |
| Title | Fluorescent zebrafish model of invasive melanoma |
| Description | "Melanoma is an increasingly common cancer with high mortality and there are currently no high throughput animal models of growth and invasion. Zebrafish is an ideal vertebrate model system for target validation and inhibitor screening where the aetiology and pathogenesis of cancer in zebrafish mirrors that in mammals. We wish to demonstrate that our zebrafish melanoma model can be used for target validation and as a drug-discovery tool using PAK4 as a proof of principle. Our model is published and validated as representative of human disease and has an advantage over previous zebrafish models because aberrant melanocyte proliferation occurs at an early larval stages which makes it amenable to high through put analysis. Tumour growth can be monitored by quantification of melanin expression and the fluorescently labelled tumour cells can be imaged in real time. We are seeking funds to strengthen our DPFS full proposal by 1. Generating a V12Ras vector with a commercially acceptable Green flourescent protein (GFP). We can then use this vector to establish a new zebrafish line at KCL as soon as we have full funding - this will significantly advance the project 2. Develop quantitative high-through-put analysis protocols for tumour growth and invasive behaviour - this will strengthen the unique aspects of the project proposal. 3. Identify siRNA sequences to knockdown zebrafish PAK4 - this will progress the proof of concept element of our proposal. Most recent work supported by DPFS Portfolio Award" |
| Type | Support Tool - For Medical Intervention |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | On hold |
| Impact | tbc |
| Title | Multiplex, coincidence detection of biomarkers |
| Description | "A significant challenge of biomedical translational research is the identification of molecular biomarkers that can be used in diagnosis, prognosis and in predicting and evaluating responses to treatments. The reliable assessment of these biomarkers in biological samples, particularly those from the clinic, has proved challenging; immunohistochemistry in this context has been poorly controlled, minimally quantified and lacking in the specificity required. Prior work has established that an optical, coincidence detection approach can drive specificity to yield spatially resolved, robust and meaningful patient data. We have now translated the principle of coincidence detection into a novel coincidence biodetector that has been tested successfully as a coincidence readout. Through the generation of a small repertoire of recombinant detectors fused to this novel coincidence readout, we now propose to establish the proof of concept for this biomarker approach Most recent work supported by DPFS Portfolio Award" |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | tbc |
| Title | NOGO Receptor ( NgR1) inhibitors for Brain Repair |
| Description | "The Nogo receptor 1 (NgR1) limits regeneration in the damaged nervous system and has been identified as a therapeutic target for a wide range of conditions including motor neuron disease (MND/ALS). A number of pharmaceutical companies have programmes to develop biological agents (e.g. antibodies) that inhibit NgR1 function (Biogen, Novartis and GSK). We have used virtual screening to identify the first small drug-like NgR1 inhibitors; however, for reasons discussed in section 4.2 below we would like to identify additional hits to advance this programme. To this end we have used similar in silico techniques to identify ~100 compounds that are closely related to the existing hits, as well as ~100 novel candidates all from the ChemBridge library of 800,000 compounds. The aim of this project is to obtain evidence that our "in-house" approach can identify novel selective NgR1 antagonists, and to use this as the starting point for seeking funding for a major drug discovery programme. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | tbc |
| Title | Novel, non-invasive clinical tool to provide a patient-specific measure of isobaric aortic stiffness in hypertensive patients |
| Description | "Need: Hypertension contributes to approximately 50% of all cardiovascular deaths (estimated 8 million deaths/year worldwide), the vast majority attributable to systolic hypertension which is related to stiffening of the aorta and great arteries. Recent studies have shown that lowering blood pressure does not normalise aortic stiffness. However, there is no clinical tool currently available to specifically assess the aortic stiffness, independent of blood pressure, for an individual patient. Solution: We will design and clinically validate a novel tool for clinical use to measure aortic stiffness through an innovative application of magnetic resonance imaging technology. Rationale: To identify high-risk individuals and tailor drug treatment aiming specifically at reducing large artery stiffness and hence mortality/morbity. Development plan: Implementation and validation of realtime MR flow techniques, providing an integrated PC-unit to display changing pulse wave velocity versus physiological parameters in real time and clinical study in hypertensive patients. s Most recent work supported by DPFS Portfolio Award" |
| Type | Diagnostic Tool - Imaging |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | tbc |
| Title | Therapeutic resolution of BMPR2 mediated signalling defects in pulmonary arterial hypertension (PAH) |
| Description | "PAH is a devastating cardiovascular disorder caused by extensive vascular remodelling of blood vessels in the lung and in the absence of effective therapy, leads to right-heart failure (1). We have demonstrated that heterozygous nonsense mutation in the type II receptor (BMPR-II) for bone morphogenetic proteins, underlie the majority of the inherited and familial forms of PAH (2). The principle aim of this project is to develop a therapy for PAH by promoting translation readthrough of pathogenic nonsense alleles using non-toxic chemical agents. Current systems are not suitable for high-throughput screening, thus we have developed a dual-fluorescence reporter assay. We now seek to enhance the development of this assay and use it to identify small molecules capable of resolving BMPR2 mediated signalling defects. Studies performed in mammalian cells and a mouse model will provide proof of principle for restoration of receptor mediated signalling by demonstrating therapeutic effecacy prior to and following the onset of PAH Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | On hold |
| Impact | tbc |
| Title | Treg sub-populations in patients with advanced kidney disease for induction of transplant tolerance |
| Description | A regulatory T cell based cell product for use in clinical trials. Most recent funding is via the EU Consortium, as above. |
| Type | Therapeutic Intervention - Cellular and gene therapies |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2012 |
| Development Status | Under active development/distribution |
| Impact | tbc |
| Title | [11]C-methionine positron emission computerised tomography in diagnosing neurofibromatosis 1 |
| Description | "Neurofibromatosis 1 (NF1) is a complex inherited disease that involves the skin and nervous system predominantly and predisposes affected individuals to the development of benign and malignant tumours. It is characterised by multiple benign peripheral nerve sheath tumours (neurofibromas). Affected individuals have a 7%-13% life-time risk of developing malignant peripheral nerve sheath tumours (MPNSTs) that ususally arise from benign plexiform neurofibromas. MPNST are challenging to diagnose and treat, frequently heralding a poor prognosis. Magnetic resonance imaging (MRI) shows the site and extent of the tumour but is not a reliable indicator of malignancy. [18]-F-fluorodeoxyglucose positron emission computerised tomography (FDG PET-CT) has enabled the selection of patients likely to have MPNST by virtue of the increased metabolic activity of the tumours, but demonstrates an overlap between benign and malignant tumours, necessitating potentially hazardous diagnostic surgery. Sensitive and specific diagnostic imaging is essential to predict MPNST grade and prognosis and to permit monitoring of response to drug therapy. [11]C- methionine PET (MET PET) will be evaluated as a diagnostic tool for NF1-MPNSTs to determine its' superiority to FDG PET. MET and FDG PET findings will be compared with tumour histology (microscopic structure) to determine its ability to predict tumour grade and prognosis. Most recent work supported by DPFS Portfolio Award" |
| Type | Diagnostic Tool - Imaging |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | tbc |