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By Alina Shrourou, on 16 June 2022
Top tips to communicate research to people living or caring for someone with a health condition. From early lab-based research all the way to new treatments and service improvements, you will gain valuable insights that benefit you, your research and ultimately patients and their carers.
Authors: Nordia Willis1, Iyamide Thomas2, Edwin Carr3 and Linda von Nerée3 (more…)
By Alina Shrourou, on 30 May 2022
In this interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdocs and non-tenured researchers at University College London (UCL), Dr Olga Kopach highlights her Regenerative Medicine Therapeutic Innovation Network (TIN) Pilot Data Fund awarded project, investigating the therapeutic potential of medicine encapsulation for treating chronic pain and nerve regeneration. (more…)
By Alina Shrourou, on 27 April 2022
In this interview as part of the Early Career Innovators series, recognising the amazing translational work of postdocs and non-tenured researchers at University College London (UCL), Dr Sarah Massey highlights her Devices & Diagnostics Therapeutic Innovation Network (TIN) Pilot Data Scheme awarded project involving the use of a mobile app to manage spasticity symptoms. (more…)
By Alina Shrourou, on 22 March 2022
In this interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdocs and non-tenured researchers at University College London (UCL), Dr Annalucia Darbey and Dr Charlotte Spicer highlight their joint Cell and Gene Therapy Therapeutic Innovation Network (TIN) Pilot Data Fund awarded project, investigating the comparison of novel gene therapies to treat an inherited neurodegenerative disorder. (more…)
By Alina Shrourou, on 15 March 2022
In this interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdocs and non-tenured researchers at University College London (UCL), Dr Ariel Finkielsztein highlights his Regenerative Medicine Therapeutic Innovation Network (TIN) Pilot Data Scheme awarded project involving the production of induced pluripotent stem cells (iPSC) for lung regeneration. (more…)
By Alina Shrourou, on 7 March 2022
In this interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdocs and non-tenured researchers at University College London (UCL), Dr Amy Richardson highlights her Cell and Gene Therapy Therapeutic Innovation Network (TIN) Pilot Data Fund awarded project based on testing a novel gene therapy for epilepsy. (more…)
By Alina Shrourou, on 1 March 2022
In this interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdocs and non-tenured researchers at University College London (UCL), Dr Apostolos Papandreou highlights his Small Molecules Therapeutic Innovation Network (TIN) Pilot Data Fund awarded project, involving novel drug development for a genetic neurodegenerative disorder.
The title of my project is ‘Development of novel autophagy inducers for the treatment of Beta-Propeller Protein-Associated Neurodegeneration (BPAN)’. It involves developing new drugs for a rare, devastating, life-limiting neurodegenerative disorder: Beta-Propeller Protein-Associated Neurodegeneration (BPAN).
In my previous work, I performed a drug screen and identified promising drugs that ‘treat’ BPAN nerve cells in the laboratory. Namely, I developed a brain model of BPAN; I converted patients’ skin cells into ‘stem cells’, which have the capacity to transform into any cell type in the body. I then manipulated these stem cells to create a specific type of brain cell (known as “dopaminergic neurons”) that are significantly affected in BPAN. I utilised this laboratory model (our “disease-in-a-dish”) to understand disease processes and confirmed that a crucial waste disposal and recycling system (termed ‘autophagy’) is defective.
I tested thousands of drugs for their capacity to treat BPAN in the dish – using both approved drugs, and others still under development. I successfully identified several promising drugs that restore autophagy in BPAN. I now want to test derivatives of the most promising of these drugs further, to identify ones with improved qualities, that can in turn be taken forward to future studies on other preclinical models and, ultimately, to a clinical trial.
BPAN is a recently identified genetic condition, emerging as the commonest form of a group of disorders known as childhood-onset Neurodegeneration with Brain Iron Accumulation (NBIA). Affected children initially present with delayed development, seizures and behavioural difficulties. A second devastating illness phase manifests in teenage years or early adulthood, with an irreversible decline in abilities (loss of independent walking and talking) and dementia. There is an urgent translational need to better understand BPAN and develop effective treatments for it.
At Great Ormond Street Hospital, we have established a nationally-recognised clinical service for children with BPAN, as well as a programme of important laboratory research at UCL. Since 2016, we have been working towards better understanding the processes causing BPAN in order to develop effective therapies.
I now plan to further develop novel drugs that have the capacity to ‘treat BPAN in the dish’, with the ultimate goal to translate these novel therapies into the clinic for my BPAN patients.
The Small Molecules TIN is an excellent platform of drug development therapeutic innovation, into which my project and research fits really well. I am an early career researcher, and the fund was addressed to people at this career stage. Moreover, I have been working within UCL over the last few years in order to develop small molecule therapies for BPAN. UCL collaborators (from the TRO Drug Discovery Group) have now created derivatives of the most promising small molecules I identified in my previous work. My plans to further test, validate and develop these molecules not only build on my previous work and hold potential for translational therapeutic benefit, but promote intra-UCL collaborations between institutes, departments, and groups. For all these reasons, I feel that the Small Molecules TIN Pilot Data Scheme will be a very suitable springboard for future therapeutic development for BPAN, and also for my development as an academic clinician with a translational focus.
This process has been a very enjoyable and educational experience. The application was well advertised and straightforward, and the form easy to fill in and to the point. Importantly, as part of the application process and interview preparation, I had the chance to attend the associated ACCELERATE training workshop. This interactive workshop taught me to better pitch my research ideas in a way that my audience can understand; it was also very useful in improving my PowerPoint presentation skills. Hints and tips were given throughout, and it was nice to work interactively with other people in similar career stages within UCL. Overall, I think the whole process is an excellent opportunity for early career researchers looking for translational funding opportunities.
I hope to test the new drug derivatives, and identify ones that work well in ‘treating BPAN’ in the dish but are also effective in much smaller concentrations. These can then be tested in other models, as appropriate, prior to clinical trials. I also hope to better elucidate the mechanism of action of these compounds, which would be interesting in its own, but would also shed light into the pathophysiological mechanisms leading to disease in BPAN.
After the TIN project, promising candidate molecules will be tested in BPAN 3-D ‘mini-brains’ that I am concurrently developing in the lab, and/ or a mouse model of BPAN that I am also aiming to establish with help of international and intra-UCL collaborators. Discussions with MHRA will guide my steps to progression towards the clinic. My ultimate goal is to develop disease modifying/curative treatments for BPAN. I also aim to become an independent clinician scientist, with a particular interest in paediatric neurometabolic disorders and a bench-to-beside approach to developing novel therapeutics for my patients.
Dr Apostolos Papandreou was born in Greece in 1981. He studied medicine there, and subsequently moved to the UK in 2007. He had all his postgraduate paediatric training and then underwent paediatric neurology subspecialty training at Great Ormond Street Hospital, London (2013-2021). His PhD studies were on novel therapeutic development for rare disorders (PhD, University College London 2020).
He is now an NIHR BRC Catalyst fellow at UCL (Great Ormond Street Institute of Child Health), continuing his research in neurometabolic and neurodegenerative conditions with a focus on developing new, disease-specific treatments; he is also an honorary Paediatric Neurology Consultant at the Evelina London Children’s Hospital (Complex Motor Disorders Service).
By Alina Shrourou, on 23 June 2021
In this Cell & Gene Therapy TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Marion Mercier highlights her Cell & Gene Therapy TIN Pilot Data Fund awarded project, involving the validation of novel gene therapies for epilepsy.
Human brain tissue is routinely excised during epilepsy surgery, and can, given the right conditions, be maintained alive in slice culture for extended periods of time. My project, entitled “Validating novel AAV gene therapies for epilepsy in human organotypic slices”, involves firstly to optimise human tissue slicing and culture protocols for the successful maintenance of this tissue, and secondly to establish efficient viral transfection methods in these human organotypic slices. The specific virus used encodes for a protein that suppresses neuronal excitability and as such is being developed as a gene therapy strategy for epilepsy. Thus, the project aims to establish a human tissue model in which to validate and screen this, and future, gene therapies for epilepsy developed within the DCEE.
Filled and stained human pyramidal cell.
Epilepsy affects 1% of the global population, and 30% of patients are pharmaco-resistant, with significant associated morbidity. Several novel gene therapies for epilepsy have recently been identified and developed within the DCEE, and offer real hope for these patients. However, while results from animal models have been promising, understanding how these genetic manipulations, and the adeno-associated viral vectors (AAVs) used to deliver them, will behave in the human brain still poses a significant challenge. Furthermore, the irreversible nature of gene therapy makes transitioning from animal models to human patients particularly risky. By establishing human organotypic slices to extend the viability of excised human brain tissue, and thereby enabling transfection with AAVs (which take 2-3 weeks to express), I aim to develop a human neuronal tissue model in which to screen and validate these novel gene therapies for epilepsy and thereby help to bridge this important translational gap.
Obtaining funding for your own independent ideas and research is particularly challenging as an early career researcher, and is often impossible without considerable preliminary data. This makes getting started on new projects, and gaining the independence necessary to progress on to more senior, permanent positions, especially difficult. Furthermore, as an early career researcher working at the intersect between clinical and more basic science, I have found the complex translational research pathway quite challenging to navigate.
I have two main objectives for the 6 months duration of the project. The first is to establish good quality human organotypic slices that are viable for up to 3 weeks, and the second is to develop effective viral transfection methods in these slices. I will be transfecting the tissue with AAV-hCaMKII-EKC-GFP, a virus that aims to increase expression of an enhanced K+ channel (EKC) in human excitatory neurons, and which has shown promise as a gene therapy strategy in animal models of epilepsy. Thus, while optimising protocols for viral transfection of human organotypic slices, I hope to also start to collect clinically-relevant data pertaining to the safety of the viral transfection and the selectivity of the expression. I am currently in the first phase of the project and have already improved the human tissue slicing protocol and started to optimise the slice culture methods.
In order to start this project, all I required was two specialised pieces of equipment and a little extra funding for consumables. The Cell and Gene Therapy TIN Pilot Data Fund is ideally suited for this, and therefore provides the perfect stepping stone for getting started and obtaining quality preliminary data with which to then apply for further funding. Furthermore, it has enabled me to progress my research in a more translational direction, and to learn more about the translational pathway and all of the steps involved in getting a therapy from the lab to the clinic. This will not only be an invaluable help in establishing and advancing this current project, but also in informing my future research plans.
We are currently in the process of determining our funding availability for the Cell & Gene Therapy TIN for 2021. Please join the Cell & Gene Therapy TIN and sign up to the TIN newsletter to keep updated.
The application process was rewarding and a great learning experience. I attended the ACCELERATE coaching session on pitching projects, through which I learnt a great deal about how to communicate my ideas effectively, concisely and convincingly. Receiving this training prior to the interview made the final pitching exercise exciting rather than daunting and made it an overall positive experience through which I received a lot of constructive feedback. This has given me more confidence in my ideas and capabilities and pushed me to be more competitive and ambitious in driving my research forward.
Dr Marion Mercier a postdoctoral researcher in Prof. Dimitri Kullmann’s laboratory within the UCL Institute of Neurology’s Department of Clinical and Experimental Epilepsy (DCEE). After an undergraduate degree in Psychology at Reading University and a year as a technician working on drug discovery for epilepsy, Marion moved to Bristol to do her PhD in the laboratory of Prof. Graham Collingridge where she studied glutamate transmission and synaptic plasticity in the hippocampus.
Throughout her postdoctoral work, her research interests have evolved at the intersect between basic and clinical neuroscience, focusing specifically on interneuron plasticity and synaptic function in both physiological states and pathological conditions such as epilepsy. Recently, she has begun to study human cortical function in resected human brain tissue, and is interested in establishing human neuronal models from this tissue in order to validate the gene therapy strategies for epilepsy currently being developed within the DCEE.
By Alina Shrourou, on 3 June 2021
In this Cell & Gene Therapy TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Ellie Crompton highlights her Cell & Gene Therapy TIN Pilot Data Fund awarded project, involving new therapies for rare disease Maple Syrup Urine Disease (MSUD).
My project is entitled “Development of novel therapies for Maple Syrup Urine Disease (MSUD)”. MSUD is a rare, paediatric, metabolic disease caused by mutations in three genes. When mutated, the body cannot produce a functional enzyme complex that is used to break down branched chain amino acids (BCAAs) in the liver. This leads to a build-up of these BCAAs and metabolic decompensation of the patient. In this project, we are attempting to treat the underlying disease pathology using a bioengineered novel therapy, developed at UCL, with the aim that this will lead to improved BCAA metabolism, provide neuroprotection and prolong survival.
Currently, MSUD patients are commonly treated with strict dietary management, or in some cases patients are offered a liver transplant to correct the underlying disease. Both of these approaches have major pitfalls. The low-protein diet needed to avoid build-up of BCAAs is often said to not be palatable and this leads to compliance issues in infants and children prescribed this diet. A lack of available donors also severely limits the possibility of liver transplant. By restoring metabolic function in MSUD patient cells, we have the potential to allow the body to produce the enzymes necessary to break down BCAAs and alleviate the need for sub-optimal diet management and transplant strategies. Furthermore, our therapy is unique because it will be relevant to all MSUD patients regardless of their specific genotype or phenotype. If successful and translated to the clinic, this has the potential to fulfil an unmet medical need.
As a Research Fellow in my first post-doctoral position, I am beginning to navigate my way around the field in which I work. Before I started this post, I was unaware of the need to start generating ideas that could lead to fellowship applications at the very beginning of your post. The need to bring in funding of your own whilst only just starting your career can be daunting, especially when a majority of grant applications require you to have certain level of seniority to be eligible. There is some pressure that ECRs need to secure grant funding to progress their career, but this can be difficult when fresh out of a PhD, with one publication and no previous track record of successful grants.
The work proposed in this project is really exciting and is definitely worth exploring. I think there are some great advantages to the novel therapy approach we are researching, and without the TIN grant, this work may not have been possible. The TIN pilot fund has given me the opportunity to generate invaluable preliminary data that can support future, larger grants. There is the age-old dilemma of needing good preliminary data for large grant applications, but having no money to generate it. The TIN funding has allowed me to begin this process. I wanted to apply for this funding to kickstart my career in the cell and gene therapy field, allowing me to build my portfolio of work only a few months after finishing my PhD.
The Cell & Gene Therapy Therapeutic Innovation Network (TIN) are offering the opportunity to appear in a resource to showcase and promote the diversity/depth and breadth of expertise within the Cell & Gene Therapy space across UCL. Appearing here will raise your profile and visibility in the field of Cell & Gene Therapy, not only across UCL but with also with external academic and industrial partners leading to rewarding collaboration and funding opportunities.
UCL Researchers in the Cell and Gene Therapy field are advised to register their details to appear in the resource. To create your research profile for inclusion please click here to complete the online form.
Applying for the TIN Pilot Data Fund was a simple process with an application form consisting of only a couple of pages, rather than a large grant application with tens of pages. This made it feel far less intimidating. After being told I was shortlisted, the offer of a coaching session from ACCELERATE to improve the three-minute, 2-slide presentation that was requested was incredibly helpful. I learnt which elements of the project and application I should highlight, and which to prepare answers to questions, but not immediately bring up. The coach was very helpful and really useful experience for my career.
Within the 6-month duration of this project I hope to generate preliminary data that can elucidate whether a broadly applicable pan-genotype approach is more beneficial, and whether novel therapy is better than other therapies currently under development. The progress of my project has been slowed considerably due to Covid-19 and the challenges this has produced, but I am hopeful that we can generate a good package of data at the end, even if it is not entirely the same as that which was proposed.
Dr Ellie Crompton is a Research Fellow within the Maternal and Fetal Medicine department at the EGA Institute for Women’s Health. After having completed her PhD at Royal Holloway, University of London, Ellie joined UCL in August 2020.
Her current research aims to use gene therapy and gene editing techniques in a range of paediatric diseases with the goal to develop potential new therapeutic approaches.
By Alina Shrourou, on 13 April 2021
In this Repurposing TIN interview as part of the Early Career Innovators series, acknowledging the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Pilar Acedo highlights her Repurposing TIN Pilot Data Fund awarded project, involving the repurposing of gene P53 reactivators to treat pancreatic cancer.
My project is entitled ‘Repurposing p53 reactivators for the treatment of pancreatic cancer’. TP53 is frequently mutated in pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic neoplasms, and these mutations are associated with poor outcomes, making mutant p53 (mtp53) an attractive target. Having higher levels of reactive oxygen species (ROS) compared to normal cells, cancer cells are more sensitive to further oxidative insult.
Building on this, in this TIN awarded project, I decided to take advantage of patient-derived models we had previously developed in our lab to assess the efficacy and mechanism of action of combining a P53 reactivator with Photodynamic Therapy (PDT), a light-based therapy which promotes ROS overproduction. I anticipate this strategy will exert a synergistic anti-tumour effect leading to oxidative damage and cell death of mtp53-harbouring cancer cells. The RNA-sequencing and efficacy data derived from this project will be used to apply for follow-on funding to move our research project down the translational pathway.
Pancreatic cancer is the 5th most deadly cancer worldwide (~432,000 deaths/year) and is projected to rank 2nd by 2030. PDAC outcomes are very poor (5-year survival rate <9%) and mtp53 expression correlate with poor prognosis. Adjuvant treatment with gemcitabine following surgery is the standard of care, however, <20% of patients are found eligible for surgery. Aggressive chemotherapy combinations, restricted to fit patients, only marginally improve outcomes so novel therapeutic strategies are urgently needed. Using a therapeutic strategy that restores the tumour suppressor functions of mtp53, and induces oxidative stress (ROS), has the potential to kill cancer cells. However, this strategy for PDAC therapy remains underexplored.
Considering the limited benefits provided by current treatment options, the variety of dysregulated signalling pathways in PDAC, and that mtp53 confers chemotherapy resistance, targeted and combination therapies hold potential to improve patient outcomes. I propose a novel approach to synergistically target the impaired antioxidative response of cancer cells, inducing extensive cell death. I expect the proposed combination to be more effective than chemotherapy alone, with significantly less systemic side effects, enabling treatment of less fit patients.
As an early career researcher in the translational research field, obtaining funding to perform your own independent research is challenging and usually requires having preliminary data already available. Gaining access to patient-derived samples can also be a tricky and slow process. I could also say, surviving in academia as an early career researcher, without a permanent position is on its own, a big challenge! I have also found it challenging to develop a network of collaborators and partnerships, particularly with industry. Moreover, understating the complexity of the translational research pathway, including intellectual property (IP), and developing an entrepreneurial mind set, requires specific training.
I had obtained some preliminary data supporting this project, but which needed further validation. The Repurposing TIN Pilot Data Fund therefore was the perfect scheme to take this work forward, while also allowing me to lead and manage a grant from scratch, fostering my career development, and supporting my career goal of becoming an independent investigator. I expect data derived from this project will attract follow-on funding to accelerate our research project into the next phase in the translational pathway.
I think the guidelines were detailed and clear. The application process was well-organised, with excellent communication from the TIN Pilot Data Fund team, of which I am very grateful for the help throughout the process. I also truly appreciated the constructive feedback and advice provided by the committee.
Learn more about the support provided through the TINs
The ACCELERATE training programme has been very important in my translational progression – I think I have attended the majority of the workshops! Prior to the submission of my application, I particularly valued the seminars on IP, Entrepreneurship Skills for Researchers and ‘Grant Writing and Data Management for Translational Research’. Additionally, the pitch coaching we received was key to winning the award.
In this proof-of-concept study, I plan to evaluate the potential of a p53 reactivator in combination with a ROS-mediated therapy as a new therapeutic strategy for pancreatic cancer, using patient-derived models available in the lab. The resulting RNA-sequencing data will improve our understanding of the mechanisms underlying PDAC vulnerability/resistance to therapy and identify new therapeutic targets. I hope this study will constitute the foundation for subsequent grant applications to move the project closer to clinical translation.
Dr Pilar Acedo, is a Senior Research Fellow at the UCL Institute for Liver and Digestive Health, in the Division of Medicine, based at the Royal Free Hospital campus. After receiving her PhD in Genetics and Cell Biology from the Autonomous University of Madrid (Spain), Pilar held a postdoctoral position at the Karolinska Institute (Sweden), before joining UCL in October 2015.
Her current research aims to generate patient-derived cancer models as preclinical tools to study disease progression and to predict treatment response. Pilar investigates novel combination therapies to treat pancreatic and bile duct tumours, using nanomedicine and light-based therapies. Her research interests also include the development of biomarkers and imaging tools for the early detection of pancreaticobiliary cancers, using non-invasive approaches (Follow Pilar on Twitter: @pilar_acedo).
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