Using zinc finger nuclease technology to generate reporter-labelled human pluripotent stem cells as a tool to optimize photoreceptor transplantation

Lead Research Organisation: Newcastle University
Department Name: Institute of Human Genetics

Abstract

Pluripotent stem cells are unspecialized cells that can be grown in the laboratory and programmed to become specialized cells of a desired type, such as blood cells, muscle cells etc. Human pluripotent stem cells can be derived in different ways, from very early embryos when they become available as surplus products during in vitro fertilization, or more generally by re-programming easily accessible cells from individuals, such as from a sample of skin cells. This possibility has led to great interest in using stem cells for therapeutic applications to treat disorders caused by loss of cells of a particular type. For example, blindness due to loss of retinal cells could in principle be treated by taking a sample of skin cells from the patient, re-programme the skin cells to make unspecialized pluripotent stem cells and then programme the resulting stem cells to give retinal cell progenitors that can be grafted into the patient's eye to give rise to retinal cells. One of the difficult problems in differentiating human pluripotent stem cells is to track the cells as they change into specialized cells and then to purify the desired specialized cells. This can be done relatively easily for mouse pluripotent stem cells by inserting genes that make reporter molecules tagged with a fluorescent that makes the cells glow under suitable conditions, but the method is very inefficient in human pluripotent stem cells. A new cutting edge technology now offers a potential solution. Zinc finger nucleases are artificially created scissors that can be designed to specifically cut both strands of DNA molecules at just one specific location. These nucleases create a gap in the DNA structure which activates the cell's response for DNA repair. Upon presence of a short DNA stretch which shows similarity to the region containing the excision but also harbouring the reporter gene, it is possible to introduce the reporter gene into the gene of interest in human pluripotent stem cells. This technology is very recent and has only been applied twice in human pluripotent stem cells; however the efficiency has been much higher than other reported methods and as such the potential applications are immense. In this proposal we seek to implement this technology to create labelled human pluripotent stem cells lines that will be used as tools to optimise cell transplantation into the degenerate retina. The retina has a very complex structure consisting of several layers of neurons that are interconnected with each other. The two main cell types that are directly sensitive to light are the rod and cone photoreceptors cells. Our group has shown that it is possible to produce human cells that have the characteristics of cones and rods from human pluripotent stem cells. Despite this progress, we are not able to select these cells amongst other cell types that arise during differentiation process. Normally cell selection is achieved using a technique called fluorescence activated cell sorting (FACS). The different cells of the body have specific proteins on their surface to which antibodies tagged with coloured or fluorescent molecules can bind, allowing us to identify and sort them using FACS, however, there are few such markers that can be used for isolating cones and rods. We intend to introduce a reporter into an important retinal gene that marks their differentiation to cone and rods. The presence of the fluorescent reporter will allow us to use the cell selection strategy mentioned above to purify these cells. We can then ask the question of whether these cells exhibit the properties associated with rods and cones using a variety of in vitro stem cell assays and electrophysiological analysis. If successful, this approach will allow us to prospectively isolate rod and cone cells, define their molecular phenotype and test their ability to restore vision in animal models of retinal disease.

Technical Summary

Blindness arising from outer retinal degeneration affects 314 million people worldwide. To date there are no effective treatments that can reverse the primary pathological abnormalities of retinal degeneration. For these reasons there is an emerging need for research into the replacement and/or reactivation of dysfunctional photoreceptors. New photoreceptors only make single synaptic connections to the inner retina, thus retinal repair by cell transplantation is a feasible approach. The only cells that have been shown to integrate successfully into host retina and restore vision are retinal cells that are already committed towards a photoreceptor fate. An equivalent human donor cell would have to be obtained from the second trimester embryo which raises ethical concerns and hence attention has been focused on differentiation of human pluripotent stem cells. Work carried out by our group and others has shown that it is possible to direct human pluripotent stem cell differentiation to cells that express photoreceptor markers in vitro, however their integration into the compromised retina in vivo is poor. This raises the question of whether the transplanted cells have matured to the correct ontogenetic stage that is needed for an efficient integration. To address this question we propose to use zinc finger nucleases to construct labelled human pluripotent stem cell lines in which a reporter gene is introduced into the endogenous loci of a key retinal transcription factor CRX shown to be expressed in postmitotic photoreceptor precursors and vital for their cell fate determination. This approach would enable isolation of photoreceptor precursors from human pluripotent stem cells, testing of their transplantation potential and full characterisation of their transcription profile with the aim of identifying cell surface markers that can be used for their easy isolation prior to transplantation.

Planned Impact

Blindness is often assumed to be avoidable or reversible with modern medicine, however many causes of blindness remain untreatable. Severe visual loss has a very significant impact on quality of life leading to social isolation and depression. Perhaps surprisingly the impact of significant visual impairment on an individual's quality of life is similar to that encountered with such devastating diseases as catastrophic stroke and cancer. Two of the most prevalent causes of blindness, namely age related macular degeneration (AMD) and hereditary retinal dystrophies (HRD), share a final common pathway of irreversible visual loss resulting from outer retinal degeneration with photoreceptor loss. AMD in particular is the most common cause of blindness in the western world. It is estimated to currently affect over 400,000 people in the UK and 8 million worldwide with a predicted increasing prevalence as the population ages and developing countries adopt the western lifestyle and diet. Although treatments are evolving for early AMD there is currently no cure, and treatments are largely palliative. Unfortunately clinical experience shows that patients are frequently seen with advanced disease, impaired vision and established outer retinal degeneration. HRD, although less prevalent, have a high health impact often causing profound visual loss from an early age. Until treatments are found that can reverse the primary pathological abnormalities in AMD and HRD, there is a need for research into the reactivation and replacement of non-functioning and lost cells within compromised outer retinal circuitry, whilst, critically, the inner retina is still intact. Transplantation of retinal progenitor cells into the eyes of such patients is a plausible and achievable treatment. Substantial evidence suggests that if such cells can be isolated and differentiated to the optimum stage for integration into the retina, then transplantation could result in the restoration of visual function. Quite apart from the obvious benefit to the patient, the ability to restore sight in these patients would have enormous social and economic benefits following the cessation of their long term palliative care. Indeed AMD is not only a major public health problem that has a devastating effect upon patients; it also has marked adverse financial consequences for the economy. An economic analysis based upon losses to gross domestic product in the USA suggests that AMD alone has an approximate $30 billion annual negative impact. The return on investment is therefore potentially high for the research costs invested in the development of new treatment modalities.

Publications

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Lako M (2018) Special Series: Transplantation of Stem Cells into the Eye. in Stem cells (Dayton, Ohio)

 
Description The purpose of this study was to generate human embryonic stem cell (hESC) lines harbouring the green fluorescent protein (GFP) reporter at the endogenous loci of the Cone-Rod Homeobox (CRX) gene, a key transcription factor in retinal development. ZFNs designed to cleave in the 3' UTR of CRX were transfected into hESCs along with a donor construct containing homology to the target region, eGFP reporter and a puromycin selection cassette. Following selection, PCR and sequencing analysis of antibiotic resistant clones indicated targeted integration of the reporter cassette at the 3' of the CRX gene, generating a CRX-GFP fusion. Further analysis of a clone exhibiting homozygote integration of the GFP reporter was conducted suggesting genomic stability was preserved and no other copies of the targeting cassette were inserted elsewhere within the genome. This clone was selected for differentiation towards the retinal lineage. Immunocytochemistry of sections obtained from embryoid bodies and quantitative RT-PCR of GFP positive and negative subpopulations purified by fluorescence activated cell sorting during the differentiation indicated a significant correlation between GFP and endogenous CRX expression. Furthermore, GFP expression was found in photoreceptor precursors emerging during hESC differentiation, but not in the retinal pigmented epithelium (RPE), retinal ganglion cells or neurons of the developing inner nuclear layer. Together our data demonstrate the successful application of ZFN technology to generate CRX-GFP labelled hESC lines, which can be used to study and isolate photoreceptor precursors during hESC differentiation.
Exploitation Route The CRX-GFP human ESC line is an extremely important tool for monitoring and improving pluripotent stem cell differentiation protocols to retinal lineages. Since the manuscript has been published we have received more than ten requests to distribute the line which we are doing using a MTA.
Sectors Education,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description 3D hiPSC derived laminated retina model
Amount £100,000 (GBP)
Funding ID NC/C016106/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Private
Country United Kingdom
Start 01/2017 
End 06/2017
 
Description 3D hiPSC derived laminated retina model
Amount £1,000,000 (GBP)
Funding ID NC/C016106/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Private
Country United Kingdom
Start 11/2017 
End 10/2020
 
Description Capacity Building in Higher Education
Amount £700,000 (GBP)
Organisation erasmus + 
Sector Public
Country United Kingdom
Start 10/2017 
End 09/2020
 
Description Demonstrating proof of principle for generating a platform technology to direct differentiation of pluripotent stem cell using Sendai Viral vectors
Amount £62,000 (GBP)
Organisation Medical Research Council (MRC) 
Department MRC Confidence in Concept Scheme
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 08/2017
 
Description ERC CONSOLIDATOR FELLOWSHIP
Amount € 1,300,000 (EUR)
Funding ID 614620 
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 06/2014 
End 05/2018
 
Description European Bank of induced pluripotent stem cells (EbiSC)
Amount € 232,500 (EUR)
Funding ID EbiSC 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 05/2014 
End 09/2016
 
Description Fight for Sight UK project grant
Amount £166,000 (GBP)
Organisation Fight for Sight 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2009 
End 03/2012
 
Description Fight for Sight project grant
Amount £170,000 (GBP)
Funding ID 1456/1457 
Organisation Fight for Sight 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2013 
End 08/2017
 
Description Fight for Sight project grant
Amount £170,000 (GBP)
Organisation Fight for Sight 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 09/2021
 
Description MRC Confidence in Concept Scheme
Amount £26,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2016 
End 09/2016
 
Description MRC Integrated Mres/PhD studentship
Amount £100,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2012 
End 08/2016
 
Description MRC UK project grant
Amount £450,000 (GBP)
Funding ID # MR/S036237/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 12/2018 
End 12/2020
 
Description MRC project grant
Amount £456,000 (GBP)
Funding ID # MR/S035826/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 12/2018 
End 12/2020
 
Description MRC/BBSRC Human iPS cell research project grant
Amount £625,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2008 
End 03/2009
 
Description Macular Disease Society PROJECT GRANT
Amount £170,000 (GBP)
Organisation Macular Society 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2014 
End 03/2017
 
Description NOVARTIS PROJECT GRANT
Amount £41,400 (GBP)
Organisation Novartis 
Sector Private
Country Global
Start 04/2012 
End 03/2013
 
Description PhD studentship
Amount £100,000 (GBP)
Organisation Newcastle University 
Department Dr William Edmund Harker Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 10/2013 
End 09/2016
 
Description RP Fighting Blindness project grant
Amount £150,000 (GBP)
Funding ID GR584 
Organisation RP Fighting Blindness 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2013 
End 12/2015
 
Description RPFB Project grant
Amount £215,000 (GBP)
Organisation RP Fighting Blindness 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 02/2021
 
Description Sabbatical fellowship/Conselleria de Sanidad (Generalitat Valenciana), and the Instituto de Salud Carlos III (Ministry of Science and
Amount £750,000 (GBP)
Organisation Spanish Ministry of Science and Innovation 
Sector Public
Country Spain
Start 09/2009 
End 12/2010
 
Description Single Cell Genomics Unit
Amount £2,000,000 (GBP)
Funding ID MR/M008886/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2015 
End 12/2015
 
Description Stem cells for biological assays of novel drugs and predictive toxicology
Amount € 2,200,000 (EUR)
Funding ID STEMBANCC 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 10/2012 
End 09/2017
 
Title donor contructs for introducing GFP reporter into the 3' UTR of CRX gene 
Description a donor construct was made to introduce GFP into the endogenous CRX locus 
Type Of Material Technology assay or reagent 
Year Produced 2013 
Provided To Others? Yes  
Impact this will enable other researchers to introduce this reporter into their human ESC and iPSC lines and monitor differentiation process 
 
Description Collaboration with Prof. Colin Johnson's group 
Organisation University of Leeds
Department Faculty of Medicine and Health
Country United Kingdom 
Sector Academic/University 
PI Contribution My group generates iPSC derived 3D retinal organoids from patients with PRPFs haploinsufficiencies which are further analysed by Prof. Johnson's group.
Collaborator Contribution My group generates iPSC derived 3D retinal organoids which are analysed using high content imaging by Prof. Johnson's group.
Impact manuscript under preparation
Start Year 2014
 
Description Collaboration with Prof. Marius Ader group on subretinal injections 
Organisation University of Dresden
Country Germany 
Sector Academic/University 
PI Contribution We have learnt the method of subretinal injections from Prof. Ader's group
Collaborator Contribution Prof. Ader group has made a significant contribution to training of two team members.
Impact collaboration just started, no outputs as yet
Start Year 2017
 
Description Roche collaboration 
Organisation F. Hoffmann-La Roche AG
Country Global 
Sector Private 
PI Contribution We are setting up collaboration with Roche pharmauceticals on pluripotent stem cell differentiation and genetic manipulation
Start Year 2014
 
Description Testing of functionality of lab made retina using MEA 
Organisation Newcastle University
Department Institute of Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution We are improving methods for generating hESC and hiPSC lab made retina.
Collaborator Contribution Dr. Sernagor's group is testing the functionality of lab made retina using MEA.
Impact collaboration, manuscript and further funding
Start Year 2009
 
Description ZFN for retinal differentiation 
Organisation Johns Hopkins University
Department Institute for Cell Engineering Stem Cell Program
Country United States 
Sector Academic/University 
PI Contribution Our aims are to use ZFN to establish reporter marked pluripotent stem cell lines for identifying optimal stages of photoreceptor emergence (for example CRX and NRL-GFP labelled cell lines) and correcting inherited mutations in patient specific pluripotent cell lines (for example RP1 patients).
Collaborator Contribution Dr Linzhao Cheng's group at John Hopkins University (Baltimore, USA) has helped us to establish the Zinc finger nuclease (ZFN) technology in our laboratory.
Impact one joint manuscript in preparation
Start Year 2009
 
Description collaboration with Prof. Luhrman's group 
Organisation Max Planck Society
Department Max Planck Institute for Biophysical Chemistry Goettingen
Country Germany 
Sector Public 
PI Contribution My group generats control and patient specific 3D retinal organoids.
Collaborator Contribution Prof. Luhrman's group performs the biochemical splicing assays.
Impact manuscript under preparation
Start Year 2016
 
Description collaboration with Prof. Robin Ali 
Organisation University College London
Department Institute of Ophthalmology UCL
Country United Kingdom 
Sector Academic/University 
PI Contribution Our research groups are testing in collaboration the engraftment of hESC/hiPSC derived photoreceptor precursors
Collaborator Contribution provision of skils, murine models and transplantation techniques
Impact succesful award from Fight for Sight UK (two year project grant)
Start Year 2010
 
Title ACT clinical trial 
Description The co-applicant of these proposals (Mr. David steel) has performed RPE transplantation in patients with Stargardt's disease as part of the multi centre ACT trial. 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2014
Development Status Under active development/distribution
Clinical Trial? Yes
Impact This is a phase I trial assessing the safety of hESC derived RPE cell transplantation into patients with severe retinal degeneration. Although the final data from this phase have not been published as yet, promising clinical results from a limited number of patients suggest that a phase II/III trial is very likely to go ahead and our centre is one of the partners involved in funding and liasons with regulatory bodies. 
URL https://clinicaltrials.gov/show/NCT01345006
 
Description Core member of committee C, BBSRC 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact member of committee C: reading and reviewing proposals, helping to shape UK policy
Year(s) Of Engagement Activity 2017,2018,2019
 
Description 2 articles for reader digest published by the Macular Disease Society 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Prof. Lako and Dr. Hallam described in two reader digest articles (respectively 2013 and 2014) the impact of their work on retinal disease understanding and modelling.

we have been asked to participate again for 2015
Year(s) Of Engagement Activity 2013,2014
 
Description Efficient stage specific differentiation of human pluripotent stem cells to photoreceptor progenitors 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited lecture at EURETINA meeting, 29th January 2012, Rome, Italy Prof. Lako gave a 30 minute lecture on the retinal differentiation from human pluripotent stem cells where BBSRC funding and project topic was recognised. 30 minute lecture

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description European Commission, Evaluator of REA-FET-OPEN-2017 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact panel member: discuss proposals and reach funding decisions
Year(s) Of Engagement Activity 2017,2018,2019
 
Description European Commission, Member of H02020 panel "Clinical Research on regenerative medicine", June 2017 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact panel member: proposal discussion and selection for funding
Year(s) Of Engagement Activity 2017,2018,2019
 
Description Insulin growth factor 1 is able to orchestrate formation of primitive ocular structures and stratified neural retina from human pluripotent stem cells 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact plenary lecture lecture at Southampton Medical School

no actual impacts realised to date
Year(s) Of Engagement Activity 2013,2014
 
Description Invited Speaker at Basel Life 2017 Stem Cell Forum, Basel, Switzerland, September 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An invited talk at stem cell forum organised by pharma.
Year(s) Of Engagement Activity 2017
 
Description Invited Speaker at the 8th Alliance for Healthy Ageing Conference, Groningen, Nov. 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An invited lecture on AMD and impacts on society and patients.
Year(s) Of Engagement Activity 2017
 
Description Invited Speaker at the MipTec 2014 - The Leading European Event for Drug Discovery 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact More than 500 industrial research participants attend this conference every year.

A collaborative research project with ROCHE is being developed following the talk at this conference.
Year(s) Of Engagement Activity 2014
 
Description Invited panellist of the European Opthalmology Futures Forum, London 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Opthalmologists from clinical and academic areas get together in this forum to learn the most recent achievements in disease understanding and drug discovery

press release plus publication
Year(s) Of Engagement Activity 2014
 
Description Invited presenting scientist at the Northern Alliance RP Meeting, Newcastle 
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 This is a regular event (2-3 times per year) in which Lako's group contributes regularly and serves to inform patients on recent progress made on treatment of retinal blindness as well as bringing the research group closer to patient needs.
Year(s) Of Engagement Activity 2015
 
Description Invited presenting scientist at the Northern Alliance RP meeting, Newcastle, 19th November 2016 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact 50 patients and their families attended the event.
Year(s) Of Engagement Activity 2016
URL http://www.retinalstemcellresearch.co.uk
 
Description Invited presenting scientists at the Northern Alliance RP Meeting, Newcastle, 16th April 2016. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact around 50 patients attended the event, asked questions and reinvited our team to attend the next local gathering.
Year(s) Of Engagement Activity 2016
 
Description Invited speaker at the RPFB patient day, 2014, Birmingham 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact more than 200 patients and their families attended the event.

We got amazing feedback from patients, how much they enjoyed the talks and how much they learnt on the recent scientific developments in the field.
Year(s) Of Engagement Activity 2014
 
Description Invited speaker at the annual research day organised by Macular Disease society UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Around 80 patients and their families attended this event. Prof. Lako and Dr. Collin delivered two talks on the impact of stem cell developments and technologies on disease modelling and understanding.

We have been asked to participate in the next's year annual event.
Year(s) Of Engagement Activity 2014
 
Description Invited speaker at the annual research day organised by RP Fighting Blindness UK 
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 more than 200 RP patients and their families attended the events as well as health professionals and researchers working in this area

we were asked to participate in the 2014 patient day event organised by RPFB
Year(s) Of Engagement Activity 2014
 
Description Keynote speaker at 13th British SCEV 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Around 100 eye clinicians attended this meeting which discussed the recent progress on stem cell and gene therapy.
Year(s) Of Engagement Activity 2015
 
Description Member of the H2020-JTI-IMI2-panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Ho2020 panel member: proposal discussion and funding, helping to share EU research policy and funding.
Year(s) Of Engagement Activity 2017,2018
 
Description Member of the H2020: SC1-BHC-09-2018 panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Ho2020 panel member: proposal discussion and funding, helping to share EU research policy and funding.
Year(s) Of Engagement Activity 2006,2017
 
Description New tools for treating human inherited diseases 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker: LivES symposium: Embryonic Stem Cells: Paris, 12-13th March 2012

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description Organiser of the Newcastle RP Patient Information Day, 8th June 2016 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact 98 patients and their families attended the event which sparked a lot of questions, discussion and increased interest in application of stem cell therapies for retinal disease.
Year(s) Of Engagement Activity 2016
URL https://campus.recap.ncl.ac.uk/Panopto/Pages/Viewer.aspx?id=d7b01a8a-3dfe-486e-b0ae-bc8d02b3e3f9
 
Description Poster presentation at 10th anniversary of ERC 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Four poster presentations from my group with broad reach to patients with retinal dystrophies and policymakers.
Year(s) Of Engagement Activity 2017
 
Description Presenter at Café Scientifique. 'Can stem cells restore vision in AMD?' Middlesbrough, 16th May 2017 
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 Talk to patients with AMD and general public
Year(s) Of Engagement Activity 2017
 
Description Presenter at the Macular Society Roadshow. 'Hopes for restoring vision in AMD with stem cells'. Hull, 11th May 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Invited talk at the event organised by the Macular Society UK
Year(s) Of Engagement Activity 2017
 
Description Presenter at the Northern Alliance RP & Usher Group event 
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 Engagement event with RP patients
Year(s) Of Engagement Activity 2017
 
Description Presenter at the Northern Alliance RP & Usher Group event. 
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 Regular engagement event with RP patients
Year(s) Of Engagement Activity 2017
 
Description Putting a finger on stem cell biology 
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 EURETINA meeting, Rome, January 2012 Invited talk to the annual EURETINA meeting which brings together clinicians, researchers and policy makers from EU countries.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description Seeing through stem cells 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker and co-chair of "pluripotent stem cell differentiation session" at the UK-ISRAEL BIRAX conference organised by the British Council in Haifa, March 2014 Abstract for published conference book

no actual impacts realised to date
Year(s) Of Engagement Activity 2014
 
Description Stem Cells for treatment of blindness:Invited speaker at the Medica meeting Dusseldorf 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact More than 500 health professionals attended this session

no actual impacts realised to date
Year(s) Of Engagement Activity 2013
 
Description Using stem cells to understand our development and human disease 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Talk

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description inaugural meeting of Stem Cell Therapy Interest Group, Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Lako: keynote speaker

This was an excellent event bringing together stem cell biologists from Glasgow and surrounding regions and great opportunity for networking.
Year(s) Of Engagement Activity 2013
 
Description invited speaker at the patient day macular society uk 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact Invited speaker: update on research funded by macular society UK
Year(s) Of Engagement Activity 2018
 
Description stem cell festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact about 300 members of the public attended the event

we have been asked to participate every year
Year(s) Of Engagement Activity 2012,2013,2014