“Pick the supervisor and not the project!”

Continuing strong with our virtual interviews we sat down with Johanna Ungerstedt, Associate Professor of Haematology and a Specialist in Haematology and Internal Medicine at the Department of Medicine Huddinge to discuss the intricacies of combining a clinical appointment with a research group and a family, as well as her journey of finding the right mentors.

Johanna Ungerstedt, MedH

The competitive and strong-willed nature of Johanna Ungerstedt was shown very early on in her life. In fact by the time she was at ‘gymnasium’ (last three years of school here in Sweden, age 16-19) she was a member of the junior national team for bridge playing and already a National and Nordic Bridge Champion- as she puts it: “it was me and roughly 500 boys!”. What an opening statement, one that we (Cancer Research KI) could not have expected, so of course there were a lot of follow-up questions! It became clear from our conversation that Johanna enjoys being challenged and has no issues with some ‘friendly’ competition. Sadly, however, we also learnt that her best friend passed away from cancer during that time-frame. As she was already contemplating a move into medical school it became quite clear to her that the next challenge she wanted to face was that of medical school coupled to research. Her journey started when she was accepted onto the KI Summer School programme, and then once in medical school at KI, onto the FOLÄK course (in English ‘Research Introduction Course for Medical Studies’). As it turns out she knew quite a few people at KI as they were her bridge tournament competition; “I soon realised that the research environment is very much like the bridge environment and I felt that I fit in immediately. I quit bridge playing after 2 years of medical school as it was impossible to keep up with everything. I wanted to get involved in research, and to seek something that was more meaningful and important than the short-lived thrill of success when you outsmart your competition in an exciting game of cards."

In search for her PhD supervisor, during medical studies, she quickly discovered that it is not always about finding the right project, as projects can change over time, but about finding an understanding supervisor that will let you grow. For her this was Professor Emeritus in coagulation research Margareta Blombäck, that gave Johanna the freedom to navigate her time and test different research ideas. Her journey post-PhD included a cutting edge 1-year postdoc at Sloan Kettering in New York to gain more pre-clinical oriented experience, a general internship as a doctor in the North of Sweden with her family, followed by what she described as “pipetting withdrawal symptoms” that resulted to a move back to Stockholm to become a pre-clinical KI postdoc. As part of her KI funded postdoc, she entered an extensive interview process with a psychologist to match her to a suitable mentor- that became a critical step. The mentor asked questions about what Johanna’s 5-year plan was, and what her career plan looked like. She didn’t actually have any answers at the time, but it forced her to think and plan, that resulted in a new challenge – a clinical residency in Haematology and Internal Medicine.

What is your WHY? 

“This is easy for a haematologist: it’s the patients!”

With a smile on her face and a small twinkle in her eye Johanna talks about how close she, and others within her profession get to their patients. In her speciality, patients are often very sick at diagnosis which prompts frequent contact with the treating physician. This results in the relationship between the doctor and the patient to become very strong in their common struggle against disease. To follow a patient’s journey which starts with a tough diagnosis, treatment as well as see their day-to-day struggle mixed with success and setbacks results in the feeling: “it’s all about the patients!”

The focus of the group

“My group works to understand the pathobiology of myeloid haematological malignancies, with focus on  chronic myelomonocytic leukemia (CMML) and systemic mastocytosis (SM). These are rare disorders hence our aim is to understand disease biology, improve diagnostics and prognostication for an individual patient, as well as to identify potential novel treatment targets. Our angle is to use primary patient samples from diagnosis and during the course of disease, and sort subsets of cells to understand what factors contribute to disease phenotype; cellular clonal involvement and transcriptional output. Both CMML and SM have been tricky to mimic in animal models, and we believe that our approach of studying primary patient cells is a good way to understand the disease, connecting genotype to clinical phenotype. I am the clinical haematology lead of the Centre of Excellence for Systemic Mastocytosis at the Karolinska University Hospital. This means that I get referrals from all over Sweden, and I have built a biobank which enables for example, studies of mast cells and mast cell progenitors, that need to be processed and analysed immediately without freezing and thawing. Here, we work closely with our collaborator Joakim Dahlin at KI, who knows when patients are scheduled and he can plan ahead for experiments in order to ensure he has access to fresh high quality samples. Sharing biobank samples in our national and international collaborations are essential to build knowledge of this disease, as SM is very rare. We have many national and international collaborators and are also part of the European Network for SM, which is essential for understanding this type of rare diseases. Together with a few colleagues, I wrote the national guidelines for Systemic Mastocytosis a couple of years ago. Given the rare nature of CMML my group is involved in several large international collaborations, in order to collect a sufficient sample size to really understand the molecular pathobiology of CMML. As an example, one of my PhD students is doing part of her PhD learning sequencing and bioinformatics in Kyoto with Professor Ogawa, and we have also been a part of several national and international epidemiological efforts to understand the heterogeneity of CMML.”

Names presented from left to right, back row: Johanna Ungerstedt, Wouter van Midden, Matilda Kjellander, front row: Kajsa Ax, Stina Söderlund, Nour Bahadi. Missing: Ebba Lundin and Linda Forsell.

What will we only know about you after we’ve worked together for a year? 

“I love my work, I work long hours and I never give up. I have a high energy level, and I think I spread energy and enthusiasm to my co-workers as well."

For over a decade Johanna has been involved in the Haematology Educational program in the Swedish Haematology Association as well as the European Haematology Association, including introducing the European Haematology Exams, as well as revising the Swedish yearly and final Haematology exams. She was the Director of Residency Studies in Haematology at Karolinska University Hospital  (ST-studierektor, 2017 to 2020) and worked hard to ensure that there is a scientific education included in the residency program, with regular journal clubs and  inspirational lectures- it’s not only about learning to diagnose and treat a certain disease. The goal is to ensure the resident doctors are involved in research. She highlights that KI  also needs clinicians in research and the resident programs are important for this, “we should make sure that their education is as good as possible, and I am not afraid to step up for what I believe in, despite a tough clinical schedule there must be time for reading and reflection.”

The triple challenge: a clinical appointment, a research group and a family

“We can talk about this for a week!” She says whilst laughing and shaking her head. Attempting to balance this type of work- life commitment is a real challenge. Johanna’s first comment and thought goes directly to her patients as she outlines below:

“As a haematologist you have a cohort of patients that you are responsible for. The upside to this is that you follow their every step and if something happens like a transformation to overt leukemia, a sudden drop in haemoglobin levels- you need to be able to see this immediately and act. This also means that you have a chance to take important biobank samples or enrol the patient into a clinical trial. You most likely have a plan in place for what to do in the event of this progression, thus the current system is beneficial for the patient. The downside is that the situation requires immediate action, and this may coincide with me not being on clinical duty.”

Johanna Ungerstedt

Johanna describes that the great advantage of having her research lab at HERM is the collaborative atmosphere with a close contact between clinical and pre-clinical groups. If Johanna is on-call over the weekend (in Swedish bakjour), and takes note of a new patient that will undergo a bone marrow examination on the following Monday, it is easy to notify her pre-clinical colleagues interested in the particular disease that is suspected that there will be a patient sample at a certain time. Thus, many patients will be included in different types of research, and no samples will be missed. “This highlights the need for more information transfer and collaboration between the clinical and pre-clinical researchers; which has been an effort driven by HERM chair Professor Eva Hellström Lindberg” when HERM was initiated.

As for family life, she has a husband that is a surgeon, three children, a dog and a big wooden sailboat that needs to be taken care of. Johanna, and her husband, had their children during the time they were in the North of Sweden and during her KI clinical postdoc appointment which helped juggle such a career choice. When it came time to starting her research group, she could ask her staff to come to whichever place she was having her rotation for lab group meetings. This is the benefit of being the boss! If the children were ill- then the group meeting could be at her home. “As a supervisor I am trying to teach those of my students who are also clinicians, to take it a step at a time and to not overload. You only have one life, and that you cannot work 100% in the clinic and have small children and do your PhD. These projects will take the time they need. From my mentors I learned that you have to have a long-term goal, with shorter interim milestones.”

The Junior Clinical Research position and the joy of long-term planning

“The Junior Clinical Research position from Cancerfonden (Swedish Cancer Society), has been absolutely crucial. When you receive a grant for 6 years you have the opportunity, and luxury, to make a long-term plan. This means that you don’t have to push projects prematurely, take unnecessary risks to complete them, and you are able to plan the safe way to execute them! If you think about it a three-year position may seem like a lot but it really isn’t. The first year goes to planning, the second to execution and by the third you have to be ready to apply for more money- and you never are. I got this position in 2018 and I am currently in my third year where we are getting ready to submit and publish a number of good quality manuscripts. Everything somehow always takes longer than planned, and unexpected things like co-workers having children, or the COVID pandemic comes and we suddenly need to adapt. In spite of this, in six years we will be able to achieve our long-term goal. For translational and even pre-clinical research this type of grant is crucial and means you can indulge in more complex long-term projects and not take the low hanging fruit!”

Cancer-related initiatives to look out for?

In general, Johanna describes that the key to cancer related initiatives are large collaborative efforts, in order to collect enough patient material to really understand disease biology. “We are involved in several such initiatives both for SM and CMML. CMML is a very heterogenous disease, and here we are currently completing a study trying to really correlate genotype to phenotype and symptoms. For the field of Haematology, heterozygous somatic mutations were described over a decade ago, the same mutations existing and many driving disease, in all myeloid haematological malignancies”. Over the last years, it has become increasingly clear that many of these mutations can also be found in the ageing healthy population, conferring an increase but still not very high risk for haematological disease. How these mutations actually drive disease and under what circumstances they can exist without initiating disease, is a large focus of the current Haematology research field, “and also a great clinical interest as we now have a patient cohort carrying mutations but no overt disease in the bone marrow, with or without mild cytopenia, who of course want to know their risk of developing disease in the future”. For CMML specifically, Johanna’s epidemiological studies have shown that some patients have cytopenia and monocytosis for years without any disease in the bone marrow, and then suddenly progress into overt CMML disease.

“Many patients with CMML have symptoms and monocytosis or thrombocytopenia for years before onset of overt CMML disease. We are currently trying to understand how the bone marrow microenvironment can switch to a permissive state allowing overt CMML disease onset.”

Johanna Ungerstedt

Reflections: what would you advise your younger self about research?

Some general advice: “Pick the supervisor and not the project. You have to choose a supervisor that understands you and that you can learn from and thrive, for 4 years (or more)! Projects can change or be modified.”

For clinical undergraduates: “If you know from before that you want to head into pre-clinical research and lead your own research group, it is not a good idea to go into a heavy clinical speciality- as this entails being busy on-call and with many clinical duties. These clinical specialities demand a lot of hands on experience- which takes a long time to achieve. Hence, it might be better to choose something with less direct patient contact and no on-site on-call duties. Frequently, these are specialities with the prefix 'clinical' something that may have a heavy work-load, but involves less patient contact- this means that it is easier to plan your time. There is a clear trend of less physicians going into translational research, and those who manage are frequently not from the very hands-on clinical specialities (like haematology).  It is wise to think twice about choosing your speciality and if this speciality is compatible with your other interests, for example research and a family life."

If we [Cancer Research KI] could wave a magic wand and do anything together, what would that look like?

After some time for deliberation, Johanna emphasised that changes in the funding systems should be considered. “I missed a lot of funding opportunities as my profile did not fit the ‘who can apply’ check-boxes given that I completed my PhD early and then performed my clinical training. I was either too merited scientifically, or too unmerited clinically! Initially I thought it was just me as I chose a slightly different career path, but over the years I have seen that there are actually many that are in the same situation, both clinical and pre-clinical researchers, especially those who want to pursue a translational research career. Overall, my opinion is that this results in a lot of talented researchers being excluded from crucial funding and opportunities."