Interview with Barbora Smolkova, 2025 Daniel Alagille Awardee

Barbora Smolkova, PhD, is a doctoral researcher at the Department of Paediatric Research at Oslo University Hospital, where she focuses on the cellular mechanisms of genetic liver diseases. Her work, which combines stem cell technologies and liver organoid models, recently earned her the prestigious Daniel Alagille Award 2025. In this interview, Barbora shares insights into her academic background, the inspiration behind her work in hepatology, and her ongoing efforts to better understand and ultimately treat rare cholestatic disorders like Aagenaes syndrome.

I hold a PhD in Biophysics, and since my master’s studies, my work has focused primarily on cellular biology. After completing my degree, I had the opportunity to spend a few months as a visiting researcher in the Department of Pediatric Research at Oslo University Hospital, where I worked with liver organoids. I was deeply impressed by both the high level of professionalism and the welcoming atmosphere of the team. When I was later offered the chance to return and contribute to research on Aagenaes syndrome, I didn’t hesitate for a moment. In today’s research, interdisciplinarity is essential, and my background has helped me see complex biomedical problems from different angle.

The Daniel Alagille Award will allow us to advance research into the molecular mechanisms underlying Aagenaes syndrome. Aagenaes disease, or lymphedema cholestasis syndrome 1, is a condition with cholestasis and lymphedema. This disease was first described by the Norwegian paediatrician Øystein Aagenæs in 1968, but its genetic cause remained unknown for the next 55 years. Our research group recently identified a variant in the 5’-untranslated region of UNC45A linked to the disease. However, the molecular mechanism still remains unclear. In this project, we use patient-derived iPSCs and liver organoids to model this genetic liver disease in the laboratory. This strategy will allow us to investigate cellular pathology, decipher critical disease mechanisms, and uncover potential avenues for therapeutic intervention.

The key goal of this research project is to understand the molecular mechanisms underlying Aagenaes syndrome. In general, genetic cholestatic diseases are rare conditions which are often overlooked in research, despite having serious effects on both patients and their families. Because of their complexity and low prevalence, they tend to receive insufficient attention and fewer resources. However, studying these conditions can not only benefit affected patients but also reveal common mechanisms that may apply to more widespread liver conditions. Understanding the biological background of the disease is essential for developing treatments that are not only more effective but also tailored to the specific mechanisms causing the condition, not just preventing the symptoms.

To study Aagenaes syndrome, we have established the foundations of this project by reprogramming PBMCs from several patients diagnosed with this syndrome into induced pluripotent stem cells (iPSCs). We then employed CRISPR/Cas9 gene editing to correct the variant in the 5’-untranslated region of UNC45A, creating isogenic iPSC controls, and from these we produced liver organoids. Currently, we are optimising liver organoid production and evaluating potential off target effects of gene editing in stem cells. The next research step is to conduct a thorough investigation of disease mechanisms spanning from the molecular level—including protein interactions and signalling cascades—to cellular dysfunction and tissue-level pathological changes.

Getting the Daniel Alagille Award has had a significant impact on my career. It has enhanced my recognition on an international level, allowing me to connect with other researchers in the field. Especially, the opportunity to attend my first EASL Congress in Amsterdam! As a group, we are now able to raise more awareness about Aagenaes syndrome, which is crucial both now and for the future. This recognition not only validates our hard work but also empowers us to push the boundaries of our research further.

It’s mostly the small things—the little moments of discovery and understanding that fuel my curiosity. Whether it’s unravelling a complex problem or learning new information that advances our research, these moments inspire me daily. I genuinely find joy in the process of expanding my knowledge, and it’s incredibly rewarding to know that my work can contribute to meaningful advancements in the field one day.

I would say that it’s not just one specific experience that has profoundly impacted me, but rather the overall opportunity to work closely with doctors and patients in the hospital. If I had to choose one story to share, it would be the moment I met a young girl with Aagenaes syndrome. She expressed her excitement about our research and how it gives her hope for better treatment. That interaction truly reinforced how much our work matters.

Don’t be afraid of failure, learn from it and start over. Just stay open minded, curious, and self-confident. And always make use of the opportunities like the Daniel Alagille Award.

Being involved with scientific organisations like EASL is extremely important, especially for early-career scientists. It offers great networking opportunities and recognition in the field. Meeting scientists who have achieved important milestones in hepatology is both inspiring and motivating. Engaging with these experts challenges me, especially when I encounter questions, I don’t have answers to. Yet, this experience encourages me to expand my knowledge. Personally, attending the EASL Congress in Amsterdam has been inspiring, as it provides a fantastic opportunity to share ideas and collaborate with others who are passionate about advancing the field.

Barbora Smolkova, PhD, is a doctoral researcher at the Department of Paediatric Research, Oslo University Hospital, specialising in cellular biology and liver organoid models to study genetic cholestatic diseases such as Aagenaes syndrome.

The Daniel Alagille Award, named after the renowned French pediatric hepatologist Prof. Daniel Alagille (1925–2005), honors his significant contributions to the field of hepatology, particularly in pediatric medicine. Prof. Alagille is best known for identifying and naming Alagille Syndrome and for his influential work that shaped the subspecialty he pioneered. The award aims to support promising young scientists dedicated to advancing research in genetic cholestatic diseases. Recipients are provided with EUR 25,000 in funding for their research over up to two years, along with a bursary to attend the EASL Congress to present their findings. This award not only acknowledges exceptional talent but also encourages the next generation of researchers to continue building on Prof. Alagille’s legacy, fostering innovation and excellence in hepatology.