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We are excited to introduce Dr. Magdalena Lorenowicz, our new principal investigator!

Magdalena joined the RMCU in 2015 with her interest for mesenchymal stem/stromal cells (MSCs). Together with her team, she is currently working to unveil the biology of MSC to improve MSC-based therapies.

Find out more about Magdalena and her research in this interview!

Hi Magdalena. Congratulations on your PI position at the RMCU!

Thank you!

What and where did you study? How did you arrive in Utrecht?

I am Polish, I studied Biotechnology in Kraków. It was quite a new faculty by then, but it is now grown with hundreds of students. There is also a new campus, it is a quite dynamic faculty! During my studies, I have been abroad for two internships. The first one in France, and the other one in Holland (Amsterdam, at the blood bank Sanquin). They offered me a PhD position in Amsterdam, so I continued living there and study the signaling underlying the migration of leukocytes in context of inflammation. After my PhD, I wanted to follow my fascination for signal transduction, by using genetic manipulation tools: this is how I ended up in Utrecht, at the Hubrecht Institute. I worked on C. elegans and migration of neuronal cells in the group of Hendrik Korswagen. This was quite a change compared to my PhD project, as I was working on cell migration from a different point of view. Migration of neurons is guided by the WNT signaling pathway, and this is actually what brought me to be interested in trafficking: we discovered a novel trafficking pathway that regulates the secretion of WNT., and it was quite cool: I appreciated the power of genetics in a model organism. C. elegans is transparent, so it is possible to follow cells in their migration, and it was so fascinating!

I then moved from the Hubrecht Institute to the UMCU, because even if I was still interested in fundamental questions, I wanted to switch to a more applied research. This is how I ended up in the department of Cell Biology, in 2012. Then, following Paul Coffer’s lab, I moved at the RMCU, back again to the Hubrecht building!

The trafficking regulation by signaling is a very fascinating topic, so I kept doing research on this, in a translatable manner. This is how I started working on MSCs and their extracellular vesicles (EVs), to understand the regulation of signaling and how could they be used in therapy. I really like the idea to apply knowledge derived from fundamental questions to clinical applications.

What do you like the most of your new position?

One of the aspects I like the most is mentoring. It is something that evolves slowly, I was already supervising some students, and I found it always very inspiring!  Younger people’s enthusiasm is refreshing, and everyone adds their own energy and perspective by working together on one subject. I enjoyed that from the beginning, I like to take a flavor from each person I am supervising into my research. I still enjoy doing it also now, having my own group. I also feel that I am building up something in a specific direction, contributing to science adding my small piece of puzzle with my own group. I think you can do it better as a team.

This brings us to my next question!
Your own group grew recently, who joined you in your research and how are they contributing to it?

I have two postdocs working in my group. Suzy Varderidou was the first one joining my team. It was a new experience for both of us, and it was really nice to start together. She is working on signal transduction by MSC-derived EVs in context of cartilage regeneration. During the lockdown period we had also time for thinking, and this inspired us to bring her expertise in mass spectrometry and knowledge into our research. She was working on neurons, and we are now interested in pursuing this direction: the therapeutic potential of MSC is quite broad, and can be applied in many conditions, neuronal disorders included. This is exactly what I like from having different people putting their own flavors into our research. If this project gets funded, it will be a nice addition to our questions.

In the end of last year, Bahar Arik joined my group as my second postdoc. She is working on another application of MSCs, in this case for protecting from Graft-versus-Host Disease. This is a project in collaboration with Caroline Lindemans’ group, and we aim to establish an in vitro system to understand the efficiency of MSC-based cell therapy. Only half of the patients receiving MSC-therapy respond to treatment, and our goal is understanding why. Graft-versus-Host Disease is a very severe condition, and it is difficult to study the molecular mechanisms in murine models. We hope that in an organoid-based coculture system could be able to answer more basic questions and let us understand why some people respond better to the treatment. Combining fundamental questions to clinical applications is what drives me the most!

There are also some students, one is joining Bahar in her project, Aina Casademont. She is originally from Spain. I really like having people in my group with their own backgrounds from different parts of the world. I also got to learn from different cultures, and supervising international people is enriching for me, one of the aspects I like the most of being a PI.

We also have another student, Vivian Hegeman, and her project is also a nice addition to our group. We are in contact with her previous supervisor, Peter van Hasselt, for the potential use of MSCs in treating lysosomal storage disorders (MPS I in particular). This is another case in which different ideas and interests add somethign to the group, while remaining focused on the main subject. I found the lysosomal disorders interesting to study, and this topic is also connected to vesicular trafficking and autophagy and my previous work. Sometimes you can go across subjects by “accident”, by keeping the main focus and interest.

What makes mesenchymal stem/stromal cells and extracellular vesicles so interesting to you?

MSCs are still a “mystery”. They have benefits to patients in the context of a broad spectrum of disorders, but we are still lacking the molecular understanding of MSC-based therapies. There are conflicting data from different centers, because there is no standardization yet. I think that the molecular understanding will solve this problem, elucidating the mechanism behind the therapeutic effect for different disorders.

I am really fascinated that I can approach the topic from a molecular view, and maybe solving the mystery! The challenges in the topic are driving me: the answers are there, we only have to ask the questions in the right way. At the moment, also with new technology available compared to the past, we can finally address fundamental questions that still wait to be answered.

The EVs field is also developing very fast.  I am confident that the technical limitations related to detection and quantification of small particles will be overcome in the near future. There are new methods for following vesicles in vivo, with switchable reporters for looking at the EV-release. Characterizing and studying EVs will contribute to our understanding of MSC biology as well. Alongside secretory factors, I believe that the cell-to-cell contacts are also very important. This is the right time to study these processes in details.

Thank you for the detailed answers! I still have some final personal questions, to get to know you better.

What do you like to do in your free time?

Free time (laughing)!

This will be a short answer at the moment. With two kids at home, free time is limited. I try to reserve an evening per week for my long-standing passion… dance! I like to dance individually, in a modern/ballet type of dancing. It is a very artistic type of dancing!

You have been in the Netherlands for quite some time now. What was the most Dutch experience you had in your time here?

Dutch experience? Mmh, I think that it would be living by agenda. That was a cultural shock when I moved here, and I am still trying to adjust to it. In Poland, people are more spontaneous in organizing social life, you can call someone and meet in 30 minutes time for a coffee. I ended up having appointments in three months’ time, a small but shocking cultural difference for me.

Follow what fascinates you: if this drives you, you should be able to reach your goals!

Do you have any advice for students and early stage researchers reading this blog?

I think it is important to stay open to follow different directions and options. We are entering a multidisciplinary era: use this opportunity, learn from different disciplines. This is also something I try to incorporate in the course I am coordinating: science is multidisciplinary, understanding each other’s language is important.

Be open for options and explore different experiences, for example during the PhD, develop different skills. Academia is quite competitive, but it is not the end of the world ending up with something that could be equally valid! Follow what fascinates you: if this drives you, you should be able to reach your goals!

Don’t be discouraged by obstacles, follow your interests! Don’t lose the drive!

This blog is written by Alessandro Cutilli, PhD candidate in Regenerative Medicine (2019-current).