From representing Sweden as a junior in international eventing competitions to promising cancer researcher with a global workplace. Her competitive streak has taken Linda Bojmar to new and exciting domains in the research community. Returning home, she will conduct studies of a type never before done in Sweden.
After a couple of years in the US, Linda Bojmar has returned to Sweden to continue her research career. The research she plans to carry out at Linköping University builds upon pilot studies from her time as postdoc in David Lyden’s lab at Weill Cornell Medicine and the Memorial Sloan Kettering Cancer Center in New York. She will examine the role of the liver in the processes that contribute to the ability of pancreatic cancer to spread as metastases in the liver.
The pre-metastatic niche
The research will look primarily at pancreatic cancer, an aggressive form of cancer with a high mortality rate and limited treatment possibilities. When the tumour cells have spread to the liver and formed secondary tumours known as metastases, the period of survival is usually short. In her research, Linda Bojmar is to investigate the early stages in the spread of tumour cells to the liver. Her hypothesis is that the liver plays an active role in this process, and that changes in the liver can either help or resist metastisation. The researchers hope to be able to measure these changes early on, before metastisation.
“We’re trying to get into what we call the pre-metastatic niche, a term that was coined by David Lyden, the principal investigator I worked with in the US. We carried out pilot studies that focused on the liver, since we knew that the cancer types we were interested in usually spread there. We also wanted to see what happens in the liver when the primary tumour grows, and how this determines whether the metastases form early, late, or not at all. We were looking for a property of the liver that we could use to slow the process, quite simply.”
Linda Bojmar is working hard to get her lab up and running in Linköping.. Photo credit John Karlsson Several animal studies have suggested that changes occur in the liver. What Linda Bojmar started when she arrived in New York was a study in humans, in which they took liver biopsies to look for changes. It’s not easy to take liver biopsies from patients. She had originally intended to start the study in Sweden before travelling to the US, but that’s not how it happened. The pilot studies in the US have now been under way for a couple of years, and the results are promising.
“After working with around 100 patients in the US, we know that taking liver biopsies doesn’t involve any major risk. The liver is easy to work with in this respect, since it regenerates itself. Now we plan to start similar work in Linköping.”
The liver biopsies are taken during surgery, but it can be difficult to follow a patient if you want to see, for example, whether the cancer comes back. In addition to the liver biopsies, Linda Bojmar and the research group will look at small particles in the blood. These particles contain proteins, and the cells can use these to communicate with each other across large distances – both in healthy people and in those with disease. The particles are known as “EVPs”, an abbreviation of “extracellular vesicles and particles”.
“These vesicles change when the cells become malignant, or if anything else happens in this microenvironment. We want to use them as biomarkers to follow the disease more easily. We are trying to correlate what we see happening in the liver to what we can detect in the blood.”
A biomarker is a biological variable that reflects a physiological change that occurs as a result of disease, drug treatment or other external influence. Biomarkers can be easily measured in, for example, blood.
We are the first to use this type of research method on humans.
Linda Bojmar outside the glazed entrance to Campus US. Photo credit John Karlsson The next natural step is to bring the research to a Swedish context and carry out the study in the Swedish population, based in Linköping.
“The concept for this type of research is starting to attract attention, and it’s starting to spread around the world, which is great. Many in vitro and in vivo studies have been carried out in animal models, but we are the first to use this type of research method on humans. If we get reliable results, we hope that this will become a new and large research field.”
The term “in vitro” is used to refer to research using cells in culture, while “in vivo” means the experiments have been done on a live subject. Most in vivo experiments are done using animals, but experiments using human volunteers are also in vivo experiments.
Linda Bojmar hopes that, as a first step, her research will help patients with pancreatic cancer. The prognosis for such patients is poor.
“You could say that we are trying to tailor treatments using the means we have available. The next step, of course, is to see whether we can discover any new molecules that we may be able to use as targets for treatment. One possible target is the immune system. The general treatments we have available today are not very effective against pancreatic cancer, but this may because we are not giving them to the right patients. It may be the case that these treatments are only effective in patients who have an active immune response. So we must be able to identify these patients, either through blood tests, or by looking at the liver or their primary tumour. This is the next step.”
The primary focus of the research is to increase survival of the patients.
“We hope that we can extend the lives of patients with pancreatic cancer, and those with cancer of the gastrointestinal system or oesophagus. Many of these types of cancer spread mainly to the liver. This is our primary focus.”
The Linköping research group
Linda Bojmar is busy getting the research fully under way in Linköping during the autumn of 2022. The ethical vetting has been carried out, and approval granted for the study on humans here in Sweden. She is looking forward to getting things started, with financing from her three main supporters: the Swedish Cancer Society, the Swedish Research Council and the Swedish Society for Medical Research (SSMF).
“We have got the Swedish study under way, and have recruited the first patients who will provide liver biopsies. We are now planning to start the studies on those with stomach and oesophageal cancer. And then we plan to start on bowel cancer. We have also started to inform other hospitals in Sweden about the studies. I’m in the process of setting up the lab – looking at where we will be located and deciding which collaborations we can initiate at LiU. At the moment, getting things properly started is what’s most exciting.”
At a later stage, additional centres in Sweden that work with pancreatic cancer will become involved.
“We are members of a Swedish network called the Swedish Study Group for Pancreatic Cancer (SSPAC), and this has supported me when I was working abroad. It is behind some of the research grants, and involves centres throughout Sweden. We will inform them about the studies and see whether we can get any more centres interested. And we plan to expand throughout the Nordic region, but that lies a few years away at the moment.”
Tell us about your research group?
A meeting of Linda’s translational research group with clinicians and preclinicians from different fields. Photo credit John Karlsson “It’s a mixed bunch. We work in a translational manner, because that’s how I want it to be. Many members are clinicians and preclinicians from different fields, doing their best to keep the projects moving forward. This is how we organised the projects in the US, as well. It’ll be very important to get these people involved.”
The group includes Hakon Andersen Blomstrand (pathologist), Anette Jönsson (research nurse), Anna Lindhoff Larsson (research nurse), Carolin Jönsson (research engineer), Linda Bojmar, Bergthor Björnsson (surgeon and associate professor), Jonas Burman (master’s student in biomedical laboratory science, and soon to be doctoral student), Per Sandström (surgeon and professor), Constantinos Zambirinis (surgical oncologist), Peter Gumberger (surgical specialist physician and soon to be doctoral student), and Elena Arlaman (soon to be research-based resident physician).
Linda Bojmar emphasises how important it is that all who are involved in the projects participate along the complete chain.
“I don’t want a surgeon to excise a piece of tissue and then not know what happens after this. I want the people in the project to participate, and this is also what they want.”
And the same applies for the students.
“Yes, the students also follow this principle. Even if a person analyses samples in a lab, I want them to know where the samples come from, who they come from, and why we are studying them. In this way, everyone sees the bigger picture, and the work becomes more fulfilling. It creates bonding in the team.”
From jodhpurs to lab coat
Even though research occupies much of her time, Linda Bojmar tries to find time for other activities. When younger, she competed for the Swedish junior eventing team. But she reached a point where she had to make a choice. She gave her last horse away on the day she started her research education, and has since then felt a deep sense of loss. She decided to put on some trainers and start running, to keep fit. While out running one day along the banks of East River in New York, she saw a sign with the symbol of a horse. Hidden in the shade of Manhattan she discovered a couple of small red barns surrounded by a fence.
The Swedish junior eventing team at the Nordic Championships in Denmark, 1999. Linda Bojmar is third from the left on her mount, Blue Steel. Sweden took gold in the team event, and Linda individual bronze.“It turned out they belonged to a couple, both more than 90 years old, who run a small riding club during the summer. I’ve been involved with this riding club in the past few years. I was really surprised to find a riding club there, just across a footbridge from the lab. It’s pretty amazing to ride in Manhattan. And most people who live there don’t know about the riding club. But a country lass like me will always find places like this,” laughs Linda Bojmar.
It’s a short walk across the footbridge from the small red barns to Manhattan and Upper East Side where she spends her days in the lab.
Love in the lab
It wasn’t just the research that was exciting in the lab – Linda also found love. She met the man who was to become her husband while working on the research project.
“He’s a clinician and was at the cancer centre with the surgeons who were working with the samples. You can say without exaggeration that we met in the lab.”
Linda Bojmar with her younger son at a research group meeting at Linköping University Hospital. Photo credit John Karlsson
I didn’t realise it would be so difficult to combine a family and this career.
The pair now has two children, and they plan to bring the whole family to Linköping. At the moment, Linda’s husband is still working in the US, and will move to Linköping University Hospital as research-focussed surgeon in the summer of 2023.
“One of the things he will have to find time for is learning the language. Our older son speaks three languages. I speak Swedish with him, my husband Greek, and we use English when talking to each other. My husband can probably manage to communicate in Swedish with a three-year-old, but not a 70-year-old patient,” she laughs.
She has given up riding at an elite level, but the competitive streak in her is still strong.
“I didn’t realise it would be so difficult to combine a family and this career. I’m always looking to win, so I’m sure I’ll make it work, somehow.”
Linda describes how living with one foot on each side of the Atlantic, small children at home, and a research project to conduct takes its toll.
“There’s not really any provisions for childcare in Sweden for children under 1 year, when they can start preschool. You have to find a solution yourself if you want to maintain progress in the research project, otherwise it’ll just stop for a year. This is something you have to consider. Research is international, and it’s difficult to just switch things off for a year if you want to remain competitive in an international context. This is the way it is, for better or for worse. Being based in Sweden will probably make things easier and will give us security. Sometimes I feel that I will become some sort of ambassador, promoting the idea of working internationally with an international family, holding a child on one arm. But I’m quite happy about doing that.”
Where will your research career be in five years’ time?
“Well, we’ll have some results from Sweden and we hope that these will confirm the results we already have from the US showing that the liver plays a role in metastisation. Maybe we’ll also have confirmed the identity of some of the target molecules in the extracellular vesicles, and will show that they can be used as treatment targets. Also, we hope to be able to use some form of drug to slow the progress, and improve in this way the situation for this group of patients. After five years, we’ll probably have started studies on other types of tumour, and will be looking for differences and similarities. We want to find out whether we can use something to stop spread to the liver in general, or whether we need to use different treatments depending on the primary tumour.”
Translation: George Farrants