Dr. Lucia Celkova
Following a competitive application process, we awarded an Emerging Researcher Award in 2022 to Dr Lucia Celkova (Trinity College Dublin) for her project ‘Establishing an iPSC-derived RPE model to study PANoptosis in RPE pathology.’ The award amount was €10,000.
Dr Lucia Celkova is currently working in the lab of Prof Sarah Doyle, Associate Professor in Immunology, Department of Clinical Medicine at the School of Medicine, Trinity College of Dublin and Head of the Immunobiology Research Group.
A key priority for Fighting Blindness is to support the next generation of vision researchers. We recognise that training, networking and developing collaborations are key to the career development of early-stage career researchers and clinicians.
Our Fighting Blindness Emerging Researcher Award supports promising early-stage researchers and clinicians in exploring or developing novel, ambitious ideas, new research directions, or finishing projects with the goal of establishing their own record of independent research.
We spoke to the Fighting Blindness Emerging Researcher Awardee, Dr Lucia Celkova, about her research.
1.What are the overall aims of the project you are working on, including how it could have an impact on those affected by sight loss?
Age-related Macular Degeneration (AMD), which affects 1 in 5 people over 70, is the leading cause of central vision loss in older adults, significantly reducing independence and quality of life. As the global population ages, AMD is expected to become a significant health and financial challenge. Despite extensive research efforts, there are currently no effective treatments for AMD because we still don’t fully understand how and why it develops.
In this project I aim to create a lab-based model of a specific type of eye cell called retinal pigment epithelium (RPE) using advanced stem cell technology. These RPE cells will be grown from human stem cells known as induced pluripotent stem cells (iPSCs). The RPE is a thin layer of specialised cells at the back of the eye that supports the retina and is crucial for normal vision. When RPE cells are damaged or die, it can lead to vision problems and even blindness. To understand how RPE cells become dysfunctional and die, researchers need reliable lab models that closely mimic how these cells behave in the human eye. This model will help us study how and why RPE cells die, a key factor in many blinding retinal diseases, including AMD.
With this model, I want to study a newly discovered form of cell death called PANoptosis, which combines several different ways cells can die into one unified process. This pathway allows a cell to find alternative ways to die if one method is blocked, making it highly efficient. PANoptosis could play a key role in AMD because it can be triggered by double-stranded RNA (dsRNA), a type of stress signal linked to the disease. Understanding PANoptosis could help us find ways to stop multiple cell death pathways at once, potentially preventing RPE cell death and vision loss. Beyond advancing our understanding of RPE degeneration, the model could also support future patient-specific studies, potentially leading to personalised treatments and new therapeutic strategies to prevent sight loss and improve outcomes for those affected.
2.Why did you get into research and what do you most enjoy about it?
I guess it was through natural curiosity that my parents encouraged from very early on in my life that I got interested in solving puzzles and discovering how things work. During my school years, I grew particularly fond of biology, chemistry and mathematics to later become fascinated by the complex functioning of human body and how all things inside it are orchestrated to keep us alive. As I didn’t feel like medicine was the right career path for me, science was the logical choice at the time. While at the beginning I wasn’t sure which scientific direction I want to pursue, when an opportunity came to choose Molecular Medicine as specialisation for my undergraduate degree, I immediately knew that this was the right fit for me. It allowed me to delve deeper into understanding various disease mechanisms, which remains my passion to this day. It also helped me to discover my specific research interest in the immune system and how it can impact disease development.
What I keep enjoying about science, and research in general, is the ability to ask virtually any question and have the available tools to find out the answer. I find it very rewarding and exciting to eventually come to the root of a problem after spending weeks (and sometimes months) trying to solve it. Research has certainly taught me not to give up and be creative about finding solutions as issues arise along the way. I also very much enjoy discussing my ideas with colleagues at conferences, sharing their perspective on my work and learning about all the different amazing endeavours by other people in research.
3.Within the next five years, where do you expect great advances to be made in vision research?
The past number of years have already seen great advances in gene therapy for inherited retinal disorders and I think this will continue to transform the available treatment options, hopefully becoming more widely available and accessible to patients. I believe that we will also see significant advancements in the area of non-inherited eye diseases, such as AMD, as the technological progress has allowed much higher throughput studies to be carried out. With tools such as RNA sequencing, spatial transcriptomics or multiomics analyses, we are now able to gain large amount of information and identify many more potential therapeutic targets. In addition, artificial intelligence (AI) has been having a tremendous impact on many different areas of life and I believe that the vision research field will be no exception, with the AI not only significantly improving patient diagnosis but also enhancing the existing tools in basic research.
4.What are your other interests?
Growing up with mountains on my doorstep, I particularly enjoy hiking and skiing. In Ireland, I have found a fantastic alternative to these in cliff walking and cycling along the coast, taking in the beautiful sceneries and sea views. I have recently re-discovered my childhood hobby of knitting and crocheting to give my mind some time to relax after a long day at work. I also enjoy all things handmade, from soap and cosmetics to cheese.
Sciencewise, I have recently got very interested in microbiome and its role in aging and disease. Having two small children, I was wondering about the impact that I was making on their future health when introducing different types of foods into their diet and as every mom does, I wanted to be sure that I was making the right choices for them. So, I started reading up and discovering more about this topic and was amazed by all the emerging evidence in relation to how our gut’s microbiota can influence many different aspects of our lives, from mental health to aging. I became particularly fascinated by the microbiome’s capacity to influence our immune responses, enhance inflammation and contribute to many chronic diseases, and how this has been impacted by our modern food processing technologies and food availability. This knowledge has now made me curious about the role that our gut microbiome could play in eye-related diseases and I would be very keen on exploring this in detail, should I, hopefully, get an opportunity in the future.
5.And last question, could you tell us a bit more about your background Lucia?
I graduated from Trinity College Dublin with a B.A. (Mod.) degree in Natural Sciences (Molecular Medicine) and an M.Sc. degree in Molecular Medicine. During my studies I became particularly interested in immunology and the role of the immune system not only in fighting infections, but also in chronic inflammatory diseases. I worked for some time as a research assistant with Prof. Helen Roche at the UCD Conway Institute studying obesity-associated inflammation, before returning to TCD to join Prof. Matthew Campbell’s lab at the Smurfit Institute of Genetics for my PhD.
During my PhD, I was involved in several projects focusing on the role of the immune system in the retina and examination of the blood-retina barrier (BRB) regulation. Excitingly, we discovered that the BRB is physiologically a very dynamic structure that periodically changes its properties throughout the day and that its disruption can lead to the development of a dry AMD-like phenotype, which was considered a breakthrough in the vision research field. Following my PhD, I was recruited by Prof. Sarah Doyle to address the role of an immune cytokine IL-36 in retinal neovascular diseases.
I subsequently diverged from the eye research for a short period of time to finish an ongoing project examining the role of IL-18 in the epidermis in the context of childhood atopic dermatitis, a skin condition affecting around 20% of children in developed countries. This helped me to gain new insights and perspective, before coming back to my main research interest, which is the study of eye-related immune responses.
In 2022, I managed to make an important step forward in my career progression towards research independence by securing my own postdoctoral fellowship and the Fighting Blindness Emerging Researcher Award, which both allowed me to pursue my own ideas and lead my own research projects based at the Smurfit Institute of Genetics and Trinity Institute of Neuroscience.
A detailed overview of Lucia’s project:
AMD is an irreversible progressive eye condition and the leading cause of central vision loss in older people, significantly impacting their quality of life and well-being, taking away their ability to recognise faces, read, drive and making performance of many routine daily tasks difficult, if not impossible, often leading to social isolation, depression and anxiety. Currently, approximately 1 in 5 people over the age of 70 suffer from the disease and as the life expectancy increases globally, AMD is expected to pose a significant health and economic burden on our aging society. Unfortunately, devastatingly for those diagnosed and their families, and frustratingly for me as a researcher, there are currently no treatments available for AMD, mainly because we still do not fully understand the pathological mechanisms leading to its development despite great efforts in recent years to address this challenge.
In this project, I wish to establish a cell culture model of the retinal pigment epithelium (RPE) derived from human induced pluripotent stem cells (iPSCs), which will subsequently allow me to study the molecular mechanisms of RPE cell death, one of the main features underlying several blinding retinal diseases, including age-related macular degeneration (AMD).
What is the RPE and why is it important?
The RPE is formed by a single layer of highly specialised cells that support the retina at the back of the eye. As such, RPE cells are indispensable for normal vision and if they become damaged, this may, sometimes very rapidly, result in visual impairment and even blindness. In order to understand how exactly these cells become dysfunctional and die, reliable and reproducible cell culture models are required that can adequately mimic and reflect the natural characteristics of the native RPE to allow us to dissect the underlying molecular processes and signalling networks. However, in the case of the RPE, such models remain rather limited. Therefore, I wish to establish a stem cell-derived RPE cell culture model that could be used to further our understanding of complex molecular mechanisms underlying RPE degeneration.
Exploring Cell Death and PANoptosis
As part of this project, I subsequently want to use this model to study a recently described concept of multifaceted programmed cell death pathway, termed PANoptosis in response to the double-stranded RNA (dsRNA), one of the AMD-associated stress signals. PANoptosis has recently been introduced as a single unified programmed cell death mechanism, integrating seemingly distinct cell death pathways. Based on this, a cell can take an alternative route to die, if one or more of the pathway(s) become compromised, suggesting that PANoptosis inhibition could simultaneously block several alternative arms of cell death and making its central master regulators ideal targets for cell death prevention.
In sum, establishment of the iPSC-derived RPE cell culture model will not only allow me to study any scientific question related to RPE function in the future but would also open up an exciting possibility of isolating stem cells directly from patients living with sight loss due to RPE-affected conditions to better understand their disease pathology and offer personalised type of therapy. Implicating PANoptosis in RPE dysfunction would represent a breakthrough in our understanding of RPE death in general, not only in response to dsRNA, and identifying any master regulators would open up novel avenues for global manipulation of programmed cell death to prevent RPE degeneration.
Emerging Researcher Award 2022 Winners Announcement
You can read here about our Emerging Researcher Award 2022 Winners Announcement