Lymphocyte ligands for the endothelial adhesion molecule vascular adhesion protein-1

Lead Research Organisation: University of Birmingham
Department Name: Clinical and Experimental Medicine

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.

Publications

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Adams DH (2018) Could endothelial TGFß signaling be a promising new target for liver disease? in Expert review of gastroenterology & hepatology

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Adams DH (2010) Mechanisms of immune-mediated liver injury. in Toxicological sciences : an official journal of the Society of Toxicology

 
Description Clinical training fellowship
Amount £220,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Research Training Fellowship
Sector Charity/Non Profit
Country United Kingdom
Start 01/2008 
End 02/2011
 
Description EME Project:12/165/31 - Targeting vascular adhesion protein-1 (VAP-1) for the treatment of liver fibrosis: a study of efficacy and mechanisms in patients with primary sclerosing cholangitis (PSC).
Amount £1,000,000 (GBP)
Funding ID EME Project:12/165/31 - Targeting vascular adhesion protein-1 (VAP-1) for the treatment of liver fibrosis: a study of efficacy and mechanisms in patients with primary sclerosing cholangitis (PSC). 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2015 
End 01/2019
 
Description Enterprising Birmingham Fund (Felicity de Cogan)
Amount £18,000 (GBP)
Organisation University of Birmingham 
Sector Academic/University
Country United Kingdom
Start  
 
Description H2020_COLLAB_HEP-CAR
Amount € 750,000 (EUR)
Funding ID 667273 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2016 
End 12/2019
 
Description MRC Project Grant
Amount £300,000 (GBP)
Funding ID G0700301 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2007 
End 02/2011
 
Description Marie Curie TOK
Amount £450,000 (GBP)
Organisation Marie Sklodowska-Curie Actions 
Sector Charity/Non Profit
Country Global
Start 04/2006 
End 03/2010
 
Description NIHR BRU
Amount £6,500,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 05/2012 
End 06/2017
 
Description NIHR BRU in Cell and Immunotherapy for LIver disease
Amount £6,500,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR Birmingham Liver Biomedical Research Unit
Sector Academic/University
Country United Kingdom
Start 09/2008 
End 09/2012
 
Description Wellcome Trust Clinical Fellowship
Amount £300,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Research Training Fellowship
Sector Charity/Non Profit
Country United Kingdom
Start 06/2011 
End 05/2015
 
Description Wellcome Trust Project grant (The role of vascular adhesion protein-1 in leucocyte transmigration across liver endothelium)
Amount £330,065 (GBP)
Funding ID 081079/Z/06/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2007 
End 03/2010
 
Title Transfectants 
Description We made mutant forms of teh protein expressed in cell lines 
Type Of Material Cell line 
Provided To Others? No  
Impact Have promoted our progress 
 
Description Clinical trial of anti-VAP-1 
Organisation Oxford University Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Academic/University 
PI Contribution Led successful EME application to fund a clinical trial involving Oxford hepatologists
Collaborator Contribution Recruitment of patients and trial design
Impact Award of grant EME Project:12/165/31 - Targeting vascular adhesion protein-1 (VAP-1) for the treatment of liver fibrosis: a study of efficacy and mechanisms in patients with primary sclerosing cholangitis (PSC).
Start Year 2013
 
Description Edinburgh 
Organisation University of Edinburgh
Department MRC Centre for Inflammation Research
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed a successful local collaboration with my colleague Dr Newsome andPorfs Forbes and Iredale in Edinburgh resulting an ongoing collaboration which ahs contributed to a recent MRC grant awarded in 2009.
Collaborator Contribution We have several ongoing collaborations sharing technology and expertise
Impact Ongoing publications and research collaborations
Start Year 2008
 
Description Levitates EU Marie Curie TOK programme 
Organisation Biotie Therapies
Country Finland 
Sector Private 
PI Contribution This is an EU funded two centre collaboration with Biotie therapies in Finland to develop VAP-1 as a theraeutic target in liver disease.
Collaborator Contribution Research collaboration and transfer of knowledge and reagentsResearch collaboration and transfer of reagents and technologies
Impact Two patents on VAP-1 as a biomarker and as a therapeutic target in liver disease. Publications in preparation Pubmed ID 17911464
Start Year 2007
 
Description Levitates EU Marie Curie TOK programme 
Organisation Biotie Therapies
Country Finland 
Sector Private 
PI Contribution This is an EU funded two centre collaboration with Biotie therapies in Finland to develop VAP-1 as a theraeutic target in liver disease.
Collaborator Contribution Research collaboration and transfer of knowledge and reagentsResearch collaboration and transfer of reagents and technologies
Impact Two patents on VAP-1 as a biomarker and as a therapeutic target in liver disease. Publications in preparation Pubmed ID 17911464
Start Year 2007
 
Description LiverMultiscan with MRI - replacing liver biopsy 
Organisation Perspectum Diagnosis
Country United Kingdom 
Sector Private 
PI Contribution One of two UK liver Centres (Edinburgh the second) involved this this project to validate 1. Production of LiverMultiscan software: led by Perspectum an Oxford spin-out company, but requiring clinician and imaging input to devlope LiverMultiscan prototype technology into a product that can be readily used in real world clinical settings; 2. Quantification of liver fibrosis using liver biopsy histology as reference standard: we with Edinburgh host large academic liver programmes, and working together, with shared transnational aspirations, we will conduct independent evaluation of the new MRI technology as compared to current standard of care, as well as to other non-invasive approaches (blood biomarkers, fibroscan), in patients with liver disease; 3. The LiverMultiscan in the context of inhomogeneous liver disease: as part of a process of generality to all liver disease, a defined pilot study of MRI scanning in patients with primary sclerosing cholangitis will be performed, the goal being to demonstrate the utility of imaging in a disease that is hetereogeneous, presently lacking therapy as well as non-invasive surrogates of disease progression for use in both clinical trials and clinical practice. 4. The LiverMultiscan against histology in ex planted liver: finally as part of the important long term validation process, Birmingham will use its unique access to fresh liver tissue to directly validate MRI findings with whole liver explant histologic findings.
Collaborator Contribution Development and testing of image analysis in liver diease
Impact TSB award to support this development
Start Year 2013
 
Description LiverMultiscan with MRI - replacing liver biopsy 
Organisation University of Edinburgh
Department Centre for Cardiovascular Science
Country United Kingdom 
Sector Academic/University 
PI Contribution One of two UK liver Centres (Edinburgh the second) involved this this project to validate 1. Production of LiverMultiscan software: led by Perspectum an Oxford spin-out company, but requiring clinician and imaging input to devlope LiverMultiscan prototype technology into a product that can be readily used in real world clinical settings; 2. Quantification of liver fibrosis using liver biopsy histology as reference standard: we with Edinburgh host large academic liver programmes, and working together, with shared transnational aspirations, we will conduct independent evaluation of the new MRI technology as compared to current standard of care, as well as to other non-invasive approaches (blood biomarkers, fibroscan), in patients with liver disease; 3. The LiverMultiscan in the context of inhomogeneous liver disease: as part of a process of generality to all liver disease, a defined pilot study of MRI scanning in patients with primary sclerosing cholangitis will be performed, the goal being to demonstrate the utility of imaging in a disease that is hetereogeneous, presently lacking therapy as well as non-invasive surrogates of disease progression for use in both clinical trials and clinical practice. 4. The LiverMultiscan against histology in ex planted liver: finally as part of the important long term validation process, Birmingham will use its unique access to fresh liver tissue to directly validate MRI findings with whole liver explant histologic findings.
Collaborator Contribution Development and testing of image analysis in liver diease
Impact TSB award to support this development
Start Year 2013
 
Description Proximagen 
Organisation Proximagen
Country United States 
Sector Private 
PI Contribution Looking at SSAO inhibitors in leukocyte trafficking
Collaborator Contribution Proximagen produce a VAP-1 antagonist
Impact n/a
Start Year 2012
 
Description Research fellowship 
Organisation Albert Ludwig University of Freiburg
Country Germany 
Sector Academic/University 
PI Contribution EU funded research fellowship for Nico Buettner to visit our laboratory for 2 years
Collaborator Contribution Funded research fellow
Impact Conference presentation Publications in preparation
Start Year 2014
 
Description VAP-1 
Organisation Biotie Therapies
Country Finland 
Sector Private 
PI Contribution On going collaboration on a liver endothelial receptor VAP-1. We have defined this as a biomarker and theraeutic traget in liver disease resulting in a recent award of an EME grant fund a proof of concept clinical trial
Collaborator Contribution Biotie therapeutic antibodies University of Turku reagents and intellectual collaboration
Impact 2 patents several publication recent EME award
 
Description VAP-1 
Organisation University of Turku
Department MediCity Research Laboratory
Country Finland 
Sector Academic/University 
PI Contribution On going collaboration on a liver endothelial receptor VAP-1. We have defined this as a biomarker and theraeutic traget in liver disease resulting in a recent award of an EME grant fund a proof of concept clinical trial
Collaborator Contribution Biotie therapeutic antibodies University of Turku reagents and intellectual collaboration
Impact 2 patents several publication recent EME award
 
Title Use of VAP-1 inhibitors to treat fibrotic diseases 
Description Use of VAP-1 as a theraeutic target for liver disease 
IP Reference TW201134484 
Protection Patent application published
Year Protection Granted 2011
Licensed No
Impact None
 
Title sVAP-1 as a biomarker in liver fibrosis 
Description We reported the use of sVAP-1 as a biomarker for liver fibrosis The present invention relates to inhibitors of VAP-1 and their use as medicaments in treating fibrotic conditions. Furthermore, the present invention relates to a method of diagnosing a fibrotic condition on the basis of elevated level of soluble VAP-1 or SSAO activity in a bodily fluid, and to a kit for use in said diagnostic method. 
IP Reference WO2011029996 
Protection Patent granted
Year Protection Granted 2011
Licensed No
Impact Second patent pending
 
Description AASLDTV on Youtube 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The film that we made for AASLDTV is now on Youtube and links have been put onto our own and other websites including the PSC Support Group Website (URL below)

There has been a great deal of interest amongst our patient support groups and we have had positive feedback from the PSC Support Group. The Chair of PSC Support, commented that "This is welcome news for patients with diseases like Primary Sclerosing Cholangitis, which currently has no effective treatment. Knowing that the unit is at the cutting edge of medicine and focused on developing novel therapies for liver disease including PSC gives such hope to patients. The unit works closely with patients and patient groups and we can be confident that these outstanding clinicians will continue to make unique breakthroughs in research and medicine to help patients with liver disease."
Year(s) Of Engagement Activity 2013
URL http://www.pscsupport.org.uk/news/exciting-era-translational-research
 
Description Development of a PPI panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact In 2009 we held an education day and recruited 20 PPI panel members who were interested in liver research. Our Liver PPI panel is now well established. Members attend meetings on liver disease and liver research twice a year. The panel contribute to the research process and collaborate with researchers on patient Information sheets, consent forms and lay summaries for academic and pharma studies and grant applications. Their comments have been pertinent and useful to the researchers- for example the panel asked for explanations of "minimal risk" and clarification of what samples would be taken in one study. They also provide positive feedback - e.g. a "scheduled procedure timetable" was of great value, "success of the study may not be of benefit to the patient but perhaps for others". In another study they raised specific questions about a definition, whether the trial was worthwhile and if the recruitment target was achievable in a sensible time frame. The panel have developed into a well- informed resource who provide invaluable and sometimes challenging feedback which has a positive benefit for the BRU research programme We have proactive PPI members (2 patients and one lay) on the strategy board who bring very different and challenging perspectives to the BRU. They provide strategic advice on stakeholder related aspects of the research programme but they also offer tactical guidance on governance and finance

The impact of the panel has been significant in several areas. The panel are now well informed and are able to offer constructive advice on our research. One panel member is assisting with literature searches and reviews. Being engaged allows PPI members to share best practice about research and to champion the research being undertaken within the BRU to the wider community. Members regularly participate in open days and public engagement events along with researchers from the BRU. They also instigated and regularly contribute to "Liver Focus" a biannual news letter on our research in liver disease. We continue to evaluate the effect of the panel through an annual survey to panel members (also part of a UHB initiative). We are developing a robust evaluation tool through the BRU that will allow them to assess the PPI panel's impact on how they deliver their research portfolio and to ensure that their involvement is positive.

Other benefits to the BRU include better designed clinical studies and trials; more accessible patient information, resulting in improvements in informed consent; education of the public about liver disease and the importance and potential of research and clinical trials
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013
URL http://www.birmingham.ac.uk/research/activity/mds/centres/liver/involvement/index.aspx
 
Description Guardian 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact -Article in the Guardian on liver disease and transplantation www.guardian.co.uk/society/2008/nov/28/organ-donation-health-policy-transplant

Incraesed public profile
Year(s) Of Engagement Activity 2008
 
Description PPI initiatve 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact 20 members of the public and patients attended a seminar/workshop on liver research in Birmingham

Panel agreed to review our research patient information sheets
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014
 
Description PSC 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Hosted meeting of the PSC patient group to discuss our research
Took on role as Trustee of the Charity in 2013

Asked to host the meeting on an annual basis
Helped develop a research funding programme for the charity
Helped write guieldlines and provide clinical advice
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013,2014
URL http://www.pscsupport.org.uk/?gclid=Cj0KEQiAp4yjBRCE_enjmpug944BEiQATCpLvU1wXwOybMo7BSFeWs_AEICLJAiy...
 
Description Public engagement 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact PSC Trust meeting London

Discussion of the potential for stem cell therapy in liver disease. A funding initiative to support genomics in liver disease.
Year(s) Of Engagement Activity 2007
 
Description Schools 
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 -Students from local schools come to the department to learn about research and to carry out short projects

Goldcrest award and Nuffield Bursary award
Year(s) Of Engagement Activity 2007,2008,2009,2010,2011,2012,2013,2014,2015
 
Description Trustee PSC Support 
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 Trustee of patients support charity responsible for overseeing charity and organising meeting to share research advances
Year(s) Of Engagement Activity 2015,2016,2017
URL http://www.pscsupport.org.uk/?gclid=CjwKEAjwqZ7GBRC1srKSv9TV_iwSJADKTjaDl5WWgqCsixq9oG84SRlUY8FyF_2U...
 
Description World hepatitis 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 Public/other audiences
Results and Impact -Hosted public meeting for World hepatitis day attended by patient groups, politicians, press. Featured on Kerrang Radio & Naked scientist website http://www.thenakedscientists.com/HTML/podcasts/specials/show/2009.06.10/

Increased profile
Year(s) Of Engagement Activity 2009