Driving Translational Biomedical Research At The University Of Leicester

Lead Research Organisation: University of Leicester

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 scheme is a key part of MRC’s translational research strategy and provides annual awards to institutions, to be used flexibly to support the earliest stages of multiple translational research projects. The award can be used by the institution to support a number of preliminary-stage translational projects. The projects supported should aim to provide sufficient preliminary data to establish the viability of an approach –– before seeking more substantive funding.  It is intended to accelerate the transition from discovery research to translational development projects by supporting preliminary work or feasibility studies to establish the viability of an approach.

Publications

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Le Provost GS (2015) ß2-adrenoceptor activation modulates skin wound healing processes to reduce scarring. in The Journal of investigative dermatology

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Maddison DC (2015) The kynurenine pathway and neurodegenerative disease. in Seminars in cell & developmental biology

 
Description Breast Cancer Now preclinical catalyst award
Amount £670,000 (GBP)
Organisation Breast Cancer Now 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2018 
End 05/2021
 
Description EPSRC grant funding - Structural biology studies of COP9 signalosome.
Amount £464,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 08/2019
 
Description Leicester Molecular Diagnostics
Amount £15,000 (GBP)
Organisation Hope Against Cancer (Rutland and Leicestershire) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2016 
End 05/2018
 
Description Neurodegeneration
Amount $50,000 (USD)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2016 
End 01/2017
 
Description PDX project
Amount £100,000 (GBP)
Organisation Hope Against Cancer (Rutland and Leicestershire) 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2017 
End 04/2019
 
Description Wellcome Trust Seed Awards in Science
Amount £100,000 (GBP)
Funding ID No 1079914/Z/15/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2015 
End 08/2017
 
Title Explant project 
Description Using an ex vivo tissue explant to model patient responses to standard of care and novel drug therapies 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2015 
Provided To Others? Yes  
Impact We have been sharing information and developing the methodology in collaboration with CRT (2015-present) and LifeArc (contract in negotiation). These data are to validate the predictive ability of the current model (with a focus on NSCLC, colon cancer, breast cancer, and endometrial cancer) to predict patient responses. We have also tested some novel agents - these data have been used (in part) to make decisions on which molecules to take forward into additional pre-clinical (including animal) models. 
 
Description ADC synthesis 
Organisation Glythera Ltd
Country United Kingdom 
Sector Private 
PI Contribution Provision of expertise and knowledge in the field. Provision of testing of novel ADC in cells in university labs by experts.
Collaborator Contribution Synthesis of ADC molecules to specific target.
Impact ADCs were produced and tested in cells. Two manuscripts are in preparation (journal for publication still to be decided) with results obtained with LD3 support. This project is ongoing as a basic research project - some additional interest has been shown by YuYu Pharma but this is not formal as yet but RF will be updated if this changes. Update March 2019
Start Year 2015
 
Description Development of novel molecules for the treatment in non-Hodgkin's lymphoma 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution We have provided structural biology information and early cellular data to provide target validation. We are now supporting a GSK lead Med Chem programme by providing complex cellular and pre-clinical models.
Collaborator Contribution GSK are providing on-going structural biology data to support a med chem programme and are also developing novel assays to demonstrate target engagement
Impact It is hoped that this programme of work will ultimately result in a 'to clinic' drug. We have completed the FastTrack part of the GSK funding scheme, which was the early lead identification phase, and have progressed onto the GSK DPAC scheme which is the lead optimisation phase of the drug discovery pipeline.
Start Year 2016
 
Description Development of novel small molecules for the treatment of non-Hodgkin's lymphoma 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution We have provided structural biology information and cell-based assay data to provide target validation. We are now supporting a GSK lead Med Chem programme by providing and running complex cellular and pre-clinical models such as explants, PDX models and PK/PD studies.
Collaborator Contribution GSK are providing on-going structural biology data to support a medicinal chemistry programme and are also developing novel assays to demonstrate target engagement.
Impact We have progressed from the GSK FastTrack award scheme of lead identification to the DPAC award scheme which is the lead optimisation phase of the drug discovery pipeline. Work is ongoing and is described in RF returns associated with other CiC grants to reduce the issue of multiple counting out outcomes. Updated March 2019.
Start Year 2016
 
Description Explant 
Organisation Cancer Research Technology (CRT)
Country United Kingdom 
Sector Private 
PI Contribution The development of tumour explant models for breast, lung and colorectal cancers (including liver metastases) to assess patient responses to current standard of care treatments. Follow on data shows that the model has a strong predictive power in prediction patient responses to therapy and survival. Going forward the plan is to use this as a 'test' system for novel compounds as part of their pre-clinical assessment.
Collaborator Contribution MCR Toxicology (Leicester) and the University of Leicester have worked in collaboration to develop the model to its current format (since 2007). The collaboration with CRT began in 2015 and encompasses access to individuals and facilities at CRT-DL (Cambridge) and work to trial a number of their novel compounds. CRT will continue the collaboration under the name of Cancer Research UK Therapeutic Discovery Laboratories and the MRCT will continue the collaboration under the name of LifeArc.
Impact A number of publications have used this methodology (prior to MRC funding) from this source. This project has now produced an additional publication, in addition to several poster presentations with published abstracts, alongside further collaborations with other tech transfer companies. Leicester University will collaborate with Cancer Research UK Therapeutic Discovery Laboratories and LifeArc to test a range of novel anti-cancer drugs, attracting investment totalling >£500K. This project received follow on CiC funding until 2017 - most recient updates have been reported against the final year of funding to prevent duplication of returns. Updated March 2019
Start Year 2015
 
Description Explant 
Organisation LifeArc
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution The development of tumour explant models for breast, lung and colorectal cancers (including liver metastases) to assess patient responses to current standard of care treatments. Follow on data shows that the model has a strong predictive power in prediction patient responses to therapy and survival. Going forward the plan is to use this as a 'test' system for novel compounds as part of their pre-clinical assessment.
Collaborator Contribution MCR Toxicology (Leicester) and the University of Leicester have worked in collaboration to develop the model to its current format (since 2007). The collaboration with CRT began in 2015 and encompasses access to individuals and facilities at CRT-DL (Cambridge) and work to trial a number of their novel compounds. CRT will continue the collaboration under the name of Cancer Research UK Therapeutic Discovery Laboratories and the MRCT will continue the collaboration under the name of LifeArc.
Impact A number of publications have used this methodology (prior to MRC funding) from this source. This project has now produced an additional publication, in addition to several poster presentations with published abstracts, alongside further collaborations with other tech transfer companies. Leicester University will collaborate with Cancer Research UK Therapeutic Discovery Laboratories and LifeArc to test a range of novel anti-cancer drugs, attracting investment totalling >£500K. This project received follow on CiC funding until 2017 - most recient updates have been reported against the final year of funding to prevent duplication of returns. Updated March 2019
Start Year 2015
 
Description Explant 
Organisation Medical Research Council (MRC)
Department MRC Toxicology Unit
Country United Kingdom 
Sector Public 
PI Contribution The development of tumour explant models for breast, lung and colorectal cancers (including liver metastases) to assess patient responses to current standard of care treatments. Follow on data shows that the model has a strong predictive power in prediction patient responses to therapy and survival. Going forward the plan is to use this as a 'test' system for novel compounds as part of their pre-clinical assessment.
Collaborator Contribution MCR Toxicology (Leicester) and the University of Leicester have worked in collaboration to develop the model to its current format (since 2007). The collaboration with CRT began in 2015 and encompasses access to individuals and facilities at CRT-DL (Cambridge) and work to trial a number of their novel compounds. CRT will continue the collaboration under the name of Cancer Research UK Therapeutic Discovery Laboratories and the MRCT will continue the collaboration under the name of LifeArc.
Impact A number of publications have used this methodology (prior to MRC funding) from this source. This project has now produced an additional publication, in addition to several poster presentations with published abstracts, alongside further collaborations with other tech transfer companies. Leicester University will collaborate with Cancer Research UK Therapeutic Discovery Laboratories and LifeArc to test a range of novel anti-cancer drugs, attracting investment totalling >£500K. This project received follow on CiC funding until 2017 - most recient updates have been reported against the final year of funding to prevent duplication of returns. Updated March 2019
Start Year 2015
 
Description Patient-Derived Xenografts to enable personalised medicine 
Organisation Ono Pharmaceutical
Country Japan 
Sector Private 
PI Contribution Working with individuals from Ono we have been using our access to a unique catalog of lymphoid cell lines to model resistance to BTK inhibition. Support has also been supplied for the development of PDX models of DLBCL.
Collaborator Contribution A member of Ono staff has been working with in Leicester to develop and assay models of BTK resistance.
Impact Outputs include - development of resistant lines, with full genetic analysis, the development of PDX models of lymphoid disease. Work ongoing with support of the Earnest and Helen Scott Haematological Institute. Models are being used to support GSK DPAc project - fully updated in other RF returns. Update March 2019
Start Year 2016
 
Description Structural Biology of the COP9 Signalosome 
Organisation Domainex
Country United Kingdom 
Sector Private 
PI Contribution The 2014/15 CiC award was used to optimise our novel in-house assays to detect the catalytic activity of the COP9 complex which along with the 2.6 A°. These data enabled us to win a competitive award from Domainex (the STAR Award for in silico screening) and we are now in the process of validating hits from the Domianex in silico screen.
Collaborator Contribution Domainex for a STAR award (awarded in July 2015 ~ value £10,000). This award has led to an in silico screen of the Domainex LeadBuilder library of 1.2 million collated 'lead-like' molecules - the outputs of which are now being validated.
Impact This partnership has ended but an application to the CRUK Structural Biology Accelerator is in preparation. Work has been ongoing by PhD Student (now supervised by Marck Carr) - PhD submission compleded 2018 and viva due early 2019. We expect a number of publication to be writing in the post viva period and will update RF with this during the next 6 months. Update March 2019
Start Year 2015
 
Title METHODS 
Description A method for improving skin scar colour matching, for example reducing scar hyperpigmentation, the method comprising administering a therapeutically effective amount of an agent, which positively modulates ß2-adrenergic receptor conformation, or receptor activity, or activation thereof, to a subject in need thereof. The subject typically is in need of improving skin scar colour matching, for example reducing scar hyperpigmentation, because the subject has or is at risk of hyperpigmentation. The subject typically is selected as being at risk of hyperpigmentation on the basis of one or more of the following factors: · the subject has previously developed hyperpigmentation of a scar • the subject tans readily on exposure to sunshine or ultraviolet (UV) radiation, rather than burning • the subject has a non-Caucasian racial origin • the subject's skin colour (for example in an area that is not tanned) is considered to be darker than that typical of a naturally fair-haired Caucasian person. The subject may be selected as being at risk of hyperpigmentation because they are at least predominantly of Chinese, black African, Asian or Southern European racial origin, and/or if their skin type can be assessed under the Fitzpatrick Scale as Type III, IV, V or VI. 
IP Reference WO2014135896 
Protection Patent granted
Year Protection Granted 2014
Licensed No
Impact This is the basis of an Biomedical catalyst funded first in man clinical trial of Salbutamol as a topical treatment.
 
Title MODULATION OF FIBROBLAST ACTIVITY 
Description The invention includes a method for simultaneously decreasing the amount of TGFß1 and increasing the amount of TGFß3 produced by a fibroblast, the method comprising contacting the fibroblast with an agent which positively modulates ß2-adrenergic receptor; a method for reducing fibroblast differentiation, the method comprising contacting the fibroblast with an agent which positively modulates ß2-adrenergic receptor; and a method of reducing the deposition of collagen in a subject, the method comprising administering to the subject an agent which positively modulates ß2-adrenergic receptor. 
IP Reference WO2009118541 
Protection Patent granted
Year Protection Granted 2009
Licensed No
Impact This was the basis for a MRC Biomedical catalyst funded first in man Phase I Clinical Trial of Salbutamol as a topical therapy.
 
Title New compounds and uses _KMO 
Description The discovery is a class of drugs that can penetrate the blood brain barrier and inhibit Kynurenine- 3-­Monoxygenase (KMO) inhibitor, one of the key enzymes in the kynurenine pathway. This pathway is crucial for catabolism of tryptophan (TRP), which has been implicated in neurodegenerative disorders including Huntington's Disease (HD). 
IP Reference GB2568549 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact This research has revealed a unique class of compounds which penetrate the blood brain barrier concentrating the active compound at the therapeutic site. This coudl be used as the basis for a number of additional neurogenerative therapies.
 
Title SENESCENCE 
Description The invention provides an inhibitor of a Tec family tyrosine kinase and uses thereof. The invention also extends to methods of treating, ameliorating or preventing senescence or an age-related disorder or a solid tumour in a subject. The invention also extends to Tec family tyrosine kinase gene-silencing molecules, pharmaceutical compositions, methods of making the compositions and compound screening assays. 
IP Reference WO2016128744 
Protection Patent application published
Year Protection Granted 2016
Licensed Commercial In Confidence
Impact Another patent application has been granted: GB2015/051480
 
Title Phase I clinical trial of Salbutamol as a topical treatment to reduce scarring 
Description This is a topical gel formulation of Salbutamol, currently being assessed in a Phase I study. The therapy is intended to reduce scarring and hyper-pigmentation of wounds, in the case of this trial, a test incision of healthy volunteers. The trial is being funded by Biomedical Catalyst (Grant ref: MR/M024679/1) 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2019
Development Status Under active development/distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier SSCART
Impact This represents a unique re-purposing of a drug therapy from an inhaled asthma product to a topical wound healing modifier. The relative low cost of the active ingredient and excellent safety profile established after many years of use, mean that successful clinical trials should lead to a widely available product. A number of previous products to reduce scarring were high cost biologics that required injections to administer, this made their cost effectiveness very limited despite having some positive results. The completion of this phase I trial will position the product for further commercial investment or acquisition. 
URL https://clinicaltrials.gov/show/NCT03514615
 
Description CR-UK outreach 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Engagement with activities organised as part of the Cancer Research UK Leicester Centre. Typically bi-annual events are put on to engage with the general public with hands on activities, talks, films and discussions (inc Q&A sessions).
Year(s) Of Engagement Activity 2015,2016
 
Description Girlguiding 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact multiple events within Girlguiding Leicestershire -
1) age appropriate hands on activities performed with girls from 4-17 to make science fun and engaging - with the purpose of promoting Science Technology Engineering and Maths (STEM) activities to young women (small groups - individual meetings and also to division/county events including camps and activity days)
2) training sessions for leaders in Girlguiding to enable/encourage them to undertake STEM activities within their units
3) to promote Women In Science and Engineering (WISE)
4) provide positive female role models
Year(s) Of Engagement Activity 2015,2016,2017,2018
 
Description MCB Open Day 
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 Schools
Results and Impact Open day to school children from across the region for widening participation purposes. Hands on activities explaining 'precision medicine' were undertaken
Year(s) Of Engagement Activity 2016,2017
URL http://www2.le.ac.uk/departments/molcellbiol/file-store/science-open-day-2016
 
Description Patient group talks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Talks about advances in drug discovery research at the University (special emphasis on lung/thoracic and haematological diseases). Typically 'after dinner style' talks with Q&A sessions.
Year(s) Of Engagement Activity 2015,2016,2017,2018
 
Description School visits 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talks given on malaria research - typically to a year group (60-80 students) - discussions, Q&A sessions to follow and careers advice given.

Typically 3-4 such events are undertaken annually.
Year(s) Of Engagement Activity 2015,2016,2017,2018
 
Description School visits to UOL 
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 Schools
Results and Impact Participation in Dynamic DNA and Richard III open days - which open up the University to children and members of the general public. Typically a mixture of hands on activities (covering science subjects and other activities of note for the University e.g. archeology). The positive effects are increased engagement with the local (and wider community) and in widening participation (making a University education more approachable for all).
Year(s) Of Engagement Activity 2015,2016,2017,2018