Elucidating splicing factor function and retinal splicing programmes: developing new therapeutic strategies for splicing factor retinitis pigmentosa
Lead Research Organisation:
Newcastle University
Department Name: Institute of Human Genetics
Abstract
Retinitis pigmentosa (RP) is a common form of hereditary, progressive sight loss: it has a prevalence of 1 in 2500 and more than 1 million people affected worldwide. A major form of RP is caused by defects ("mutations") in genes that encode protein components ("splicing factors") of the "spliceosome". The spliceosome is a complex of proteins that ensure the new RNA transcripts formed ("transcribed") from genes are then correctly spliced to form the final messenger or mRNA. The cell then uses the final mRNA to encode the production of proteins. Splicing removes non-coding RNA ("introns") from the essential coding regions ("exons") that encode proteins. An analogy is the editing of unwanted or nonsensical passages out of a set of instructions, so that only intelligible words and sentences remain in the final text. The spliceosome is the cellular apparatus that performs the editing and ensures the fidelity and specificity of splicing.
RP caused by mutations in splicing factors is a perplexing condition because splicing is ubiquitous in cells, but the condition only causes the degeneration of retinal cells. Previous work has suggested that mis-splicing of genes that encode retinal proteins may be important. However, our recently published work suggests that defective splicing of components of the splicing apparatus itself is the fundamental molecular defect. This positive feedback loop appears to only occur in retinal cells, suggesting that the targeting of this process might be particularly effective as a possible treatment. This work developed experimental methods and applied them to understand the function of PRPF31 in RP. In the present proposal, we now wish to broaden our investigations to include PRPF8, since this is a key structural component at the heart of the spliceosome and is essential for correct splicing. Mutations in PRPF8 are also a major cause of splicing factor RP.
In order to understand this mechanism of disease in greater depth and to assess potential treatments, we will use special cell systems that closely model human retinal tissue. We will use patient-specific human stem cells differentiated into retinal cells, allowing us to study cellular structures and functions in retinal tissue derived from patients with splicing factor RP. These investigations would be impossible if we were to rely on the very limited clinical resources of patient tissue, inappropriate cell models such as skin fibroblasts, or the available mouse mutants that do not recapitulate the human disease. We will use biochemical methods to understand the effect of PRPF8 mutations on the structure and function of the spliceosome. We will combine these studies with "next generation" or clonal sequencing to determine the nucleotide sequences of RNA from patient-derived retinal tissue. This will determine which tissue is first affected during retinal degeneration, what types of splicing defects occur and which genes are affected. These studies will then inform the design of pre-clinical studies into potential treatments of PRPF8-related RP, for example by specific ablation ("knock-down") of the mutant form of the protein in retinal cells.
The outcome of this proposed research will establish the disease mechanisms for RP caused by mutations in PRPFs, specifically PRPF8 and PRPF31, enabling the development of future therapeutic strategies to treat splicing factor RP. Current clinical trials for ocular gene therapies have focused on severe, early-onset disorders such as retinal dystrophies. However, there remains a large and unmet clinical need for the treatment of adult-onset RP, a large proportion of which are due to defects in PRFPs. These conditions present a particular challenge because patients can have useful residual vision into their fifth decade. A clear understanding of disease mechanism and greater requirement to demonstrate safety is therefore required before proceeding to clinical trials.
RP caused by mutations in splicing factors is a perplexing condition because splicing is ubiquitous in cells, but the condition only causes the degeneration of retinal cells. Previous work has suggested that mis-splicing of genes that encode retinal proteins may be important. However, our recently published work suggests that defective splicing of components of the splicing apparatus itself is the fundamental molecular defect. This positive feedback loop appears to only occur in retinal cells, suggesting that the targeting of this process might be particularly effective as a possible treatment. This work developed experimental methods and applied them to understand the function of PRPF31 in RP. In the present proposal, we now wish to broaden our investigations to include PRPF8, since this is a key structural component at the heart of the spliceosome and is essential for correct splicing. Mutations in PRPF8 are also a major cause of splicing factor RP.
In order to understand this mechanism of disease in greater depth and to assess potential treatments, we will use special cell systems that closely model human retinal tissue. We will use patient-specific human stem cells differentiated into retinal cells, allowing us to study cellular structures and functions in retinal tissue derived from patients with splicing factor RP. These investigations would be impossible if we were to rely on the very limited clinical resources of patient tissue, inappropriate cell models such as skin fibroblasts, or the available mouse mutants that do not recapitulate the human disease. We will use biochemical methods to understand the effect of PRPF8 mutations on the structure and function of the spliceosome. We will combine these studies with "next generation" or clonal sequencing to determine the nucleotide sequences of RNA from patient-derived retinal tissue. This will determine which tissue is first affected during retinal degeneration, what types of splicing defects occur and which genes are affected. These studies will then inform the design of pre-clinical studies into potential treatments of PRPF8-related RP, for example by specific ablation ("knock-down") of the mutant form of the protein in retinal cells.
The outcome of this proposed research will establish the disease mechanisms for RP caused by mutations in PRPFs, specifically PRPF8 and PRPF31, enabling the development of future therapeutic strategies to treat splicing factor RP. Current clinical trials for ocular gene therapies have focused on severe, early-onset disorders such as retinal dystrophies. However, there remains a large and unmet clinical need for the treatment of adult-onset RP, a large proportion of which are due to defects in PRFPs. These conditions present a particular challenge because patients can have useful residual vision into their fifth decade. A clear understanding of disease mechanism and greater requirement to demonstrate safety is therefore required before proceeding to clinical trials.
Technical Summary
Alternative splicing is a pre-mRNA processing step that removes or includes specific exons/introns enabling generation of multiple isoforms from a single gene. Mutations in pre-mRNA splicing factors (PRPFs) cause 15-20% of autosomal dominant retinitis pigmentosa (adRP). It is unknown how mutations in ubiquitously expressed splicing factors cause retinal disease. In collaborative work, we have used patient-specific induced pluripotent stem cells (iPSC) differentiated to retinal cell-types to show that PRPF31 haploinsufficiency results in reduced spliceosome activity, defective splicing and impaired ciliogenesis in retinal pigment epithelium (RPE) and photoreceptors. Building upon these multidisciplinary skills and expertise, we aim to focus on a key essential structural component of the activated spliceosome, PRPF8, in order to identify genes and functional pathways that are affected by splicing factor dysfunction and their contribution to adRP. Mechanistic insights into splicing regulation of key candidate genes will inform the development of proof-of-concept splice-correcting gene therapies for RP.
The specific aims of this proposal are to:
1) use RNA-seq, quantitative proteomics and cellular assays to determine the effect of PRPF8 mutations on retinal cell structure and function, and identify mis-spliced genes and dysregulated splicing programmes;
2) use biochemical & in vivo splicing assays to assess the effect of PRPF8 mutations on splicing kinetics, and spliceosome assembly, stability, activity and function;
3) use RNA-Seq/iCLIP-Seq to identify the physiological & disease relevant RNA-binding sites of PRPF8 in the nucleus and cytoplasm;
4) use splice-switching morpholino oligonucleotides to validate the candidate mis-spliced transcripts in retinal cells;
5) gain insights into functional & splicing defects in PRPF8-related RP to develop new targeted therapeutic interventions, leading to translation into Phase I clinical trials for PRPF8-RP.
The specific aims of this proposal are to:
1) use RNA-seq, quantitative proteomics and cellular assays to determine the effect of PRPF8 mutations on retinal cell structure and function, and identify mis-spliced genes and dysregulated splicing programmes;
2) use biochemical & in vivo splicing assays to assess the effect of PRPF8 mutations on splicing kinetics, and spliceosome assembly, stability, activity and function;
3) use RNA-Seq/iCLIP-Seq to identify the physiological & disease relevant RNA-binding sites of PRPF8 in the nucleus and cytoplasm;
4) use splice-switching morpholino oligonucleotides to validate the candidate mis-spliced transcripts in retinal cells;
5) gain insights into functional & splicing defects in PRPF8-related RP to develop new targeted therapeutic interventions, leading to translation into Phase I clinical trials for PRPF8-RP.
Planned Impact
The completed research will have outputs that will have the following impacts, benefiting both basic and translational research:
1) Reagents
Patient-specific iPSCs and isogenic controls will be deposited in the European Bank of Induced Pluripotent Stem Cells (EbiSC). Various constructs generated during the lifetime of this project will form an essential resource and will be deposited at Addgene.
2) Data sharing
The research programme will generate large amounts of RNA-Seq and proteomic data. These will be stored in standard formats, with standards-compliant metadata, to ensure that data are easily shared with other researchers. All raw sequence data and initially mapped data will be deposited in established public repositories including NCBI SRA (Short Read Archive), NCBI Gene Expression Omnibus and ProteomeXchange. High content imaging data will be in the form of indexed .tiff files and associated meta-data that will be up-loaded to open access microscopy-based phenogenomic resources ("Image Data Repository" https://idr-demo.openmicroscopy.org/, "Mineotaur" http://www.mineotaur.org/).
3) Publications
Data sets will be valuable to other researchers, so we will publish a "marker paper" and other peer-reviewed publication to enable new users to assess our data and existing users to cite their usage of our resource. We will disseminate our research findings and data sets to the scientific community through presentations at national and international conferences. All published work will be open-access and will be deposited in PubMed Central Universities' ePrints facilities, Research Gate, etc. in accordance with RC-UK, HEFCE and EU policies. Publications will acknowledge the support received from RC-UK.
4) Clinical and translational research advances
Retinitis pigmentosa (RP) comprises a heterogeneous group of rare inherited conditions (1 in 2500) and remain difficult to diagnose and treat. In the UK, about 23,000 patients are affected. There are very few preventative treatments or new therapeutic interventions that may modify disease progression or the long-term outlook of patients. The identification of new disease pathways in RP may enable the future rational design of therapeutics to modify or treat retinal degeneration or disease progression, or improve the long-term outlook of patients with RP. Since these conditions result from reduced levels of normal protein or dominant negative effects of mutant protein, they can in principle be corrected by gene-replacement or allele-specific knock-down, therapeutic approaches that are currently undergoing Phase III clinical trials. Patients who carry splicing factor mutations may therefore be given a clearer prognosis and enable them to be prioritized as patients that can most benefit from future targeted therapies. Next generation sequencing projects have shown that somatic mutations in splicing factors (PRPF8, U2AF1, SRSF2, SF3B1 etc.) are common in myeloid neoplasms and associated with specific phenotypes. While the focus of this application is deeper understanding and design of therapeutic interventions for PRPF8-RP, identification of PRPF targets and their functional validation will have far-reaching significance in other common clinical conditions such as blood cancers.
5) Intellectual Property (IP)
The proposed funding will produce foreground IP that will lead directly to 'composition of matter' patent filings. These will protect siRNA sequences that demonstrate the greatest efficacy at restoring the normal phenotype, and will be broad enough to protect any sequences that have 70% sequence identity to the lead targets. Prof. Lako has engaged with the technology transfer officer at Newcastle University and prior art searches have been conducted. These searches indicate that patent filings in this area primarily focus on up-regulation of the wild type allele. Therefore, our proposed strategy in modulating the expression of the mutant allele is innovative.
1) Reagents
Patient-specific iPSCs and isogenic controls will be deposited in the European Bank of Induced Pluripotent Stem Cells (EbiSC). Various constructs generated during the lifetime of this project will form an essential resource and will be deposited at Addgene.
2) Data sharing
The research programme will generate large amounts of RNA-Seq and proteomic data. These will be stored in standard formats, with standards-compliant metadata, to ensure that data are easily shared with other researchers. All raw sequence data and initially mapped data will be deposited in established public repositories including NCBI SRA (Short Read Archive), NCBI Gene Expression Omnibus and ProteomeXchange. High content imaging data will be in the form of indexed .tiff files and associated meta-data that will be up-loaded to open access microscopy-based phenogenomic resources ("Image Data Repository" https://idr-demo.openmicroscopy.org/, "Mineotaur" http://www.mineotaur.org/).
3) Publications
Data sets will be valuable to other researchers, so we will publish a "marker paper" and other peer-reviewed publication to enable new users to assess our data and existing users to cite their usage of our resource. We will disseminate our research findings and data sets to the scientific community through presentations at national and international conferences. All published work will be open-access and will be deposited in PubMed Central Universities' ePrints facilities, Research Gate, etc. in accordance with RC-UK, HEFCE and EU policies. Publications will acknowledge the support received from RC-UK.
4) Clinical and translational research advances
Retinitis pigmentosa (RP) comprises a heterogeneous group of rare inherited conditions (1 in 2500) and remain difficult to diagnose and treat. In the UK, about 23,000 patients are affected. There are very few preventative treatments or new therapeutic interventions that may modify disease progression or the long-term outlook of patients. The identification of new disease pathways in RP may enable the future rational design of therapeutics to modify or treat retinal degeneration or disease progression, or improve the long-term outlook of patients with RP. Since these conditions result from reduced levels of normal protein or dominant negative effects of mutant protein, they can in principle be corrected by gene-replacement or allele-specific knock-down, therapeutic approaches that are currently undergoing Phase III clinical trials. Patients who carry splicing factor mutations may therefore be given a clearer prognosis and enable them to be prioritized as patients that can most benefit from future targeted therapies. Next generation sequencing projects have shown that somatic mutations in splicing factors (PRPF8, U2AF1, SRSF2, SF3B1 etc.) are common in myeloid neoplasms and associated with specific phenotypes. While the focus of this application is deeper understanding and design of therapeutic interventions for PRPF8-RP, identification of PRPF targets and their functional validation will have far-reaching significance in other common clinical conditions such as blood cancers.
5) Intellectual Property (IP)
The proposed funding will produce foreground IP that will lead directly to 'composition of matter' patent filings. These will protect siRNA sequences that demonstrate the greatest efficacy at restoring the normal phenotype, and will be broad enough to protect any sequences that have 70% sequence identity to the lead targets. Prof. Lako has engaged with the technology transfer officer at Newcastle University and prior art searches have been conducted. These searches indicate that patent filings in this area primarily focus on up-regulation of the wild type allele. Therefore, our proposed strategy in modulating the expression of the mutant allele is innovative.
Publications
Armstrong L
(2023)
Editorial: Methods and advances in induced pluripotent stem cells-ophthalmology
in Frontiers in Cell and Developmental Biology
Atkinson R
(2024)
PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects
in Nature Communications
Best S
(2022)
Molecular diagnoses in the congenital malformations caused by ciliopathies cohort of the 100,000 Genomes Project.
in Journal of medical genetics
Best S
(2022)
Uncovering the burden of hidden ciliopathies in the 100 000 Genomes Project: a reverse phenotyping approach.
in Journal of medical genetics
Best S
(2022)
Unlocking the potential of the UK 100,000 Genomes Project-lessons learned from analysis of the "Congenital Malformations caused by Ciliopathies" cohort.
in American journal of medical genetics. Part C, Seminars in medical genetics
Chichagova V
(2023)
Incorporating microglia-like cells in human induced pluripotent stem cell-derived retinal organoids
in Journal of Cellular and Molecular Medicine
Dorgau B
(2022)
Human Retinal Organoids Provide a Suitable Tool for Toxicological Investigations: A Comprehensive Validation Using Drugs and Compounds Affecting the Retina.
in Stem cells translational medicine
Georgiou M
(2022)
Activation of autophagy reverses progressive and deleterious protein aggregation in PRPF31 patient-induced pluripotent stem cell-derived retinal pigment epithelium cells
in Clinical and Translational Medicine
Description | Generation and transplantation of hypoimmunogenic pluripotent stem cell derived photoreceptor precursors into a mouse model of advanced retinal degeneration: a proof-of-concept study for the USH2A and RP treatment |
Amount | £250,000 (GBP) |
Organisation | Retina UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2023 |
End | 05/2025 |
Description | Harnessing the power of patient specific organoids to discover new therapeutic treatments for Retinoblastoma |
Amount | £200,000 (GBP) |
Organisation | Little Princess Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2025 |
Description | Off-the-shelf hypoimmunogenic photoreceptors for treatment of blinding retinal disease |
Amount | € 2,500,000 (EUR) |
Funding ID | EP/Y031016/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2024 |
End | 02/2029 |
Description | SCILS Consortium: "Studying Ciliary Signalling in Development and Disease" |
Amount | € 8,000,000 (EUR) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 06/2020 |
End | 12/2023 |
Description | To assess the engraftment of hESC-derived photoreceptors and their ability to restore vision in early and advanced stages of Retinitis Pigmentosa. |
Amount | £1,100,000 (GBP) |
Funding ID | MR/X001687/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2023 |
End | 08/2026 |
Description | To establish PRPF31-AAV based gene augmentation in RPE and photoreceptor cells and assess its efficacy in restoring RPE and photoreceptor function |
Amount | £299,000 (GBP) |
Organisation | Retina UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2022 |
End | 06/2025 |
Title | patient specific PRPF31 and PRPF8 iPSC lines |
Description | PRPF31 iPSC lines have been deposited to EbiSC for enabling access to all researchers. PRPF8 patient iPSC lines are being characterised and will be also deposited to EbiSC. |
Type Of Material | Cell line |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Several research groups are already using PRPF31 iPSC lines for their work in disease modelling and gene therapy. |
Title | transcriptomic, iClip and proteomics data of PRPF8 retinal organoids and RPE cells + single cell RNA-seq data of PRPF8 retinal organoids |
Description | The trimmed FASTQ data for bulk RNA-Seq of all samples included in this study were uploaded to SRA under the accession number BioProject ID PRJNA989762 and GEO under the accession number GSE236702. The mass spectrometry proteomics data have been deposited to the ProteomeXchange under the accession number PXD043645. The single cell RNA-Seq data have been deposited to the GEO under the accession number GSE235866. The iCLIP-Seq data have been uploaded to Annotare under the accession number E-MTAB-13171. |
Type Of Material | Database/Collection of data |
Year Produced | 2024 |
Provided To Others? | Yes |
Impact | open access use by the research community |
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 | building a tissue bank form patients with inherited retinal disorders |
Organisation | University of Leeds |
Department | Vision Research Group |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We generate fibroblasts from skin biopsies and use those to derive patient specific induced pluripotent stem cells which can be used for disease modelling |
Collaborator Contribution | Prof. Chris Inglehearn and Dr Martin McKibbin (University of Leeds) are providing for us skin samples from a variety of patients with inherited retinal disorders. The aim of this work is to establish a bank of induced pluripotent stem cells from a large group of patients which can be used as tools for understanding disease pathology and drug screening. |
Impact | not yet |
Start Year | 2010 |
Description | collaboration with Merck Pharmauceticals |
Organisation | Merck |
Country | Germany |
Sector | Private |
PI Contribution | My group provides retinal organoids for in vitro testing of retinotoxic substances. |
Collaborator Contribution | The Merck scientists in the in vitro toxicology group provide advise and reagents for the crack it retina challenge project. |
Impact | paper published together, Hallam et al. Stem cells 2018 |
Start Year | 2017 |
Description | collaboration with Novartis and Roche. |
Organisation | Novartis |
Country | Global |
Sector | Private |
PI Contribution | My group generates retinal organoids for in vitro testing of retinotoxins. This is part of the NC3R 3D retina challenge project. |
Collaborator Contribution | The scientists at Novartis and Roche provide guidance for characterisation of retinal organoids after exposure to toxins. |
Impact | joint manuscript, Hallam et al. Stem Cells 2018 |
Start Year | 2017 |
Description | collaboration with Prof. Luhrman's group |
Organisation | Max Planck Society |
Department | Max Planck Institute for Biophysical Chemistry Goettingen |
Country | Germany |
Sector | Academic/University |
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's group, King's College London |
Organisation | King's College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My group has generated PRPF31 and PRPF8 retinal models which we are using to understand the pathogenesis of retinitis pigmentosa caused by mutations in these two important splicing factors. |
Collaborator Contribution | Prof. Ali's group is generating PRPF31.AAV particles to supplement PRPF31 in the patient specific retinal organoids and RPE cells. |
Impact | There have been four publications arising from this joint work as follows: PMID: 35297555 PMID: 34395430 PMID: 30315276 The fourth publication "Dysregulation of hBrr2 helicase by PRPF8 disrupts human spliceosome kinetics and 5´-splice site selection, revealing tissue-specific alternative and cryptic splicing defects" has been provisionally accepted by Nature communications. |
Start Year | 2021 |
Description | Genetics matters |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Genetics Matters is an annual event organised by Newcastle University focusing on rare diseases and their diagnosis and treatment. My research team organises a table showcasing our work in eye disease and stem cells. |
Year(s) Of Engagement Activity | 2024 |
Description | Genetics matters |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Genetics matters is an annual event organised by Newcastle University to celebrate Rare Disease Research day. Research groups organise a table each showcasing their work. Members of the public visit each table, engaging with the researchers and their projects. |
Year(s) Of Engagement Activity | 2023 |
Description | Invited Speaker at the Department of Biological Sciences, Durham University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invited speaker at University of Durham, talk focusing on application of retinal organoids for disease modelling, cell transplantation and drug discovery. |
Year(s) Of Engagement Activity | 2022 |
Description | Invited speaker at ERN workshop ""New therapeutic approaches for inherited retinal diseases", Valencia, Spain, 2023 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Prof. Lako was invited speaker at this event attended by members of the ERN consortium, patients and members of various retinal charities. |
Year(s) Of Engagement Activity | 2023 |
Description | Keynote speaker at Women in Vision UK Annual Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Prof. Lako was invited to give the Keynote lecture on this prestigious meeting that brings together UK women scientists working in vision research. |
Year(s) Of Engagement Activity | 2022 |
Description | Keynote speaker at the Organoid workshop, University of Leeds |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Prof. Lako delivered the keynote lecture on this organoid workshop. |
Year(s) Of Engagement Activity | 2022 |
Description | Member of Freigeist scientific fellowship assessment panel, December 2020 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | I was member of Freigeist scientific fellowship assessment panel, December 2020, evaluating long term fellowships focusing on pluripotent stem cell derived retinal organoids and applications. |
Year(s) Of Engagement Activity | 2020 |
Description | Prof. Lako - invited speaker at the ERN-EYE 4th scientific workshop |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Prof. Lako described her group's work on modelling rare disease in the lab using organoids and primary tumour tissue |
Year(s) Of Engagement Activity | 2021 |
Description | Prof. Lako invited to give a talk at the UCI Centre for Translational and Vision Research Distinguished Speakers |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Prof. Lako delivered a research talk on this prestigious seminar series. |
Year(s) Of Engagement Activity | 2022 |
Description | Prof. Lako: invited speaker University of Manchester |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Prof. Lako delivered a research talk focusing on application of retinal organoids for basic biology studies, disease modelling, cell transplantation and drug repurposing. |
Year(s) Of Engagement Activity | 2023 |
Description | Prof. Lako: invited speaker at the UK Eye Genetics Meeting |
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 | Prof. Lako described her group's work on enrichment of LSCs and single cell analyses of adult human cornea. |
Year(s) Of Engagement Activity | 2021 |
Description | Speaker at the The 3DMM2O Conference: 3D Hybrid Organotypic Systems |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | interesting and stimulating discussions following my talk |
Year(s) Of Engagement Activity | 2021 |
Description | Speaker at the Winter Anatomy Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | > 100 RESEARCHERS ATTENDED THE CONFERENCE. I enjoyed the discussion after the talk, which sparked lots of interesting ideas. |
Year(s) Of Engagement Activity | 2021 |
Description | invited speaker at ISER 2023 Gold Coast Australia |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Prof. Lako was session organiser and speaker at the ISER 2023 in Gold Coast Australia. |
Year(s) Of Engagement Activity | 2023 |
Description | • Keynote speaker at the 11th Mercia Stem Cell Alliance scientific meeting, Nottingham 2023 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Prof. Lako invited to give the keynote lecture in this event attended by postgraduate students and industrial partners. |
Year(s) Of Engagement Activity | 2023 |