PMI Pioneer Perspectives
In the Pioneer Perspectives series, PMI brings you closer to the people behind some of the ideas and discoveries that have shaped the field. In each portrait, a leading researcher reflects on the experiences, choices and people that have influenced their scientific journey – and shares lessons and advice for the next generation of researchers.
Pioneer Perspective: Kirsten Grønbæk
Professor Kirsten Grønbæk is a Danish haematologist and clinician-scientist whose research bridges basic and clinical science to better understand, prevent, and ultimately improve the treatment of blood cancers. One of her most highly cited publications, a review article on cancer epigenetics co-authored with Professor Peter Jones, was published in PMI.
What is your field of research, and how would you explain it to someone outside your field?
I am a haematologist, and throughout my career I have researched a broad range of blood diseases. Over the past decade, my research has focused on what happens before blood cancers, such as leukaemia, actually develop. We now know that around 10% of healthy people over the age of 60 carry genetic mutations in their blood stem cells that are identical to those found in leukaemia. However, most of these individuals never develop cancer. The key question is therefore not simply who carries these mutations, but why some people progress to disease while others remain healthy. This has become a rapidly evolving field over the past decade.
What particularly motivates our work is the possibility of intervention before cancer develops. It is one thing to identify people at increased risk, but quite another to offer them something that may prevent disease. We study individuals who have these mutations together with subtle abnormalities in their blood counts—an intermediate stage on the path towards leukaemia. These patients can participate in clinical trials investigating whether safe interventions, such as vitamin C, metformin, or exercise, might slow or prevent disease progression. The aim is to test safe, well-tolerated interventions and ultimately determine whether they could be used as genuine preventive strategies for the approximately 10% of older people who carry these genetic mutations.
What inspired you to pursue a career in this field?
My career – and my entire life – has been shaped as much by coincidence as by careful planning. After graduating from medical school, jobs were scarce, so I accepted a position in oncology. Because the on-call service was shared with haematology, I quickly discovered that this field fascinated me much more.
My first attempt at research was discouraging. After reviewing more than 2,400 patient records, I was told that I was not suited for research. For a while, I seriously considered giving up.
The turning point came when I attended a course at Hammersmith Hospital in London, where I met researchers who encouraged me to join their group. More importantly, I found a mentor, Elisabeth Ralfkiær, who believed in me, helped me secure funding, and introduced me to an inspiring environment where basic science and clinical medicine worked hand in hand. That experience shaped the way I have approached research ever since, always trying to keep one foot in the laboratory and the other in the clinic.
After seven years devoted mainly to research, I came to Rigshospitalet to complete my clinical training in haematology. Shortly afterwards, Professor Niels Borregaard encouraged me to apply for funding to establish my own laboratory. Looking back, that was another pivotal moment in my career and allowed me to continue combining laboratory research with clinical medicine.
Later, almost by chance, I attended a small scientific meeting on DNA methylation alongside a much larger conference. There I met Peter Jones – one of the pioneers of cancer epigenetics. I think I made an impression when we went for a run together. I happened to be training for a marathon at the time – something I had neglected to mention – so he was rather surprised that I managed to outrun him. That was the beginning of a collaboration that has continued ever since.
Looking back, many defining moments in my career have come from being open to unexpected opportunities rather than following a fixed plan.
Scientific discovery is exciting, but what gives me the greatest satisfaction is seeing young researchers develop. Creating an environment where people enjoy coming to work, support one another, and grow as scientists has always been very important to me.
Watching students and postdoctoral fellows evolve from inexperienced trainees into confident, independent researchers is incredibly rewarding. Several of my former trainees now lead their own research groups, and seeing them succeed probably makes me prouder than anything else in my career.
Of course, I still enjoy discovering new biology, but helping the next generation build successful careers is what I value most.
What has been the most exciting or surprising finding in your career so far?
One of the most surprising findings came from one of our vitamin C clinical trials. We expected to observe modest molecular changes, but what surprised us was how clearly we could detect biological effects directly in patients’ blood cells after one year of treatment.
We found that vitamin C appeared to alter specific genomic regions involved in blood cell development, precisely where vitamin C-dependent enzymes are expected to function. Even more remarkably, these effects were seen only in patients with a functional TET2 enzyme, perfectly matching the clinical responses we observed. Although these findings still require confirmation in larger studies, they provided compelling biological evidence that vitamin C has measurable biological effects in patients that align with the observed clinical outcomes, beyond what we had anticipated.
For me, that was a genuine moment of scientific surprise – seeing such clear biology emerge from patients rather than from an experimental model.
What has been the biggest challenge you have had to overcome as a researcher?
Early in my career, being told that I was not suited for research was undoubtedly one of the greatest challenges I faced. Fortunately, I met mentors who believed in me, and that experience taught me not to let other people’s opinions define my ambitions.
Research has continued to challenge me in different ways. Even today, I still find speaking in front of large audiences intimidating. I am always relieved when the talk is over, even though I enjoy communicating science. Sometimes I think that if I had just 10% of the confidence that some of my male colleagues seem to possess, things might have been a little easier.
Who or what has influenced or motivated you the most throughout your career?
Perhaps most importantly, I have learned that resilience matters. Whenever someone suggested that I could not do something, it strengthened my determination to prove them wrong, so I think a certain amount of grit has been essential throughout my career.
Beyond that, the people I have met along the way have had the greatest influence on my career. Several mentors appeared at exactly the right time and changed my trajectory.
Elisabeth Ralfkiær believed in me when I had almost lost confidence in myself and helped me establish my research career. During my seven years at the Danish Cancer Society, I continued collaborating with Elisabeth and worked with Per Guldberg, who taught me the fundamentals of molecular biology and genetics and how to work in the laboratory. Peter Jones introduced me to an international scientific network and long-term collaborations, while Niels Borregaard encouraged me to establish my own laboratory. Looking back, each of them opened doors that I would probably not have opened on my own.
What advice would you give to early-career researchers today?
Find good mentors – and preferably more than one. Build relationships with people you trust, because every researcher encounters setbacks, and it makes an enormous difference to have experienced people you can turn to for advice.
Get out into the world. Seek out courses, conferences, international meetings, even small ones. An international research stay during your PhD is also a great way to meet future collaborators. Some of the most important collaborations in my own career began with conversations at meetings that I almost did not attend.
If possible, spend time abroad. Looking back, one of my few regrets is that I never had the opportunity to spend a longer period working internationally. I had planned to spend time in the United States during my PhD, but those plans had to be cancelled after I developed a repetitive strain injury from years of pipetting. It is not the most common occupational injury for a PhD student, but it probably says something about how much time I spent in the laboratory. Those experiences abroad broaden your scientific perspective and create collaborations that can shape your career for decades.
