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30. Sept. 2022
The 7th edition of the Purkyne Foundation Award ceremony for the best manuscripts published in impacted journals for 2021 took place in September 2022. Among the winners was Vaclav Seda from CEITEC Masaryk University (MU) and the Department of Internal Medicine, Hematology and Oncology of the University Hospital Brno and from the Faculty of Medicine of Masaryk University. The evaluation committee selected the best publications in each category, taking into account the impact factor (IF) and the overall quality of the submitted manuscripts. In the award-winning publication, Vaclav Seda described a fundamental finding in the biology of chronic lymphocytic leukaemia (CLL), the most common leukaemia in adults. Václav Šeda and his colleagues from the laboratory of Marek Mraz have discovered how cancer cells regulate their migration in the patient's body and, above all, how they survive treatment with drugs from the group of so-called BCR inhibitors.
Read the interview with the talented molecular biologist Vaclav Seda. For which publication did he receive the Purkyne Foundation Award, and what is the focus of his research? What are his plans and career dreams?
You won the award in the 2021 competition for the best manuscript published in impacted journals. Can you describe the main findings presented in your manuscript?
The award went to our paper titled FoxO1-GAB1 axis regulates homing capacity and tonic AKT activity in chronic lymphocytic leukemia, published in Blood. As the title suggests, we show that GAB1 protein is responsible for the migration and survival of malignant B cells and their adaptation to treatment with BCR inhibitors.
In the first part of the study, we elucidate a previously unknown mechanism by which chronic lymphocytic leukemia (CLL) cells decide whether it is the right time to leave the peripheral blood and travel back to the lymphoid organs. This seemingly simple process is crucial for CLL cells. It is within the lymphoid organs where the CLL cells receive important signals for their survival and, above all, for the initiation of their proliferation. It is thus clear that stopping the migration process has quite interesting clinical potential. The mechanism we have described shows that CLL cells in the peripheral blood gradually produce and accumulate the GAB1 protein, which from a certain amount onwards, begins to facilitate the migration of CLL cells back to the lymphoid organs.
The gradual production of GAB1 protein is also the second mechanism that leads to a gradual increase in the activity of the AKT molecule in CLL cells, thus enhancing their survival in the peripheral blood. This is particularly important in the context of treatment with so-called BCR inhibitors, whose administration increases the level of GAB1, which in turn helps to activate the AKT molecule, making the malignant cells capable of surviving the treatment for a long time. In this work, we show for the first time that this adaptive mechanism can be blocked by novel GAB1 inhibitors.
To explain it with a simplified analogy, the whole second mechanism reminds me a bit of the traffic situation in Brno in the summer. The road workers close one important road (administration of a BCR inhibitor), but the clever drivers immediately find a detour (the emergence of CLL cell adaptation to the therapy). So, for a traffic collapse, there is nothing easier than to discover the detour and close it (administration of a GAB1 inhibitor).
What does this award mean to you?
I see the award as a great honour, which I appreciate immensely. Dozens of high-quality publications entered the competition, but ours impressed the judging committee enough to award it first place. Personally, I also take it as a message that the issues that my colleagues and I addressed in the publication are of significant importance and that it makes sense to continue working on them. The other dimension is, of course, the personal one, because the fact that I have received this award will also make my whole family happy.
What are your plans for the future?
First of all, I would like to finish the projects I am currently working on, which are partly related to the award-winning publication - for example; I am currently working on the preparation of a new generation of GAB1 inhibitors. Firstly, I see quite an interesting potential in them, and secondly, this type of project never lets you fall into a routine. As the project progresses, one is constantly faced with new challenges and the need to learn new things and initiate new collaborations. Moreover, it is rare in basic to applied research that one has the opportunity to experience cooperation on a substantial part during the development of a promising inhibitor.
I dare not say where science will take me in the long run. I'd like to travel for a while, try a different work style, establish collaborations, and maybe even get a different perspective on the research itself. But I am clear about one thing - I am not one of those people who would prefer to work in a prestigious lab at the expense of the interest of the topic. Therefore, my future actions will be influenced by the project topics offered and, of course, by my partner’s opinion and wishes.
What else would you like to achieve in your career?
If by asking this question you are referring to the classic science career path "PhD - postdoctoral fellowship - research group leader", I am afraid I will try to avoid the last one. Although the position of the research group leader is a symbol of scientific freedom, it also often means a change in working style and a significant increase in managerial work at the expense of the more fun lab work. For me personally, it would be ideal to be a kind of forever postdoc.
If the question is meant much more generally, then I admit, and I won't be an exception, that I'd be thrilled to see all that effort and work will result in something useful to people, whether it be a theoretical description of an important mechanism or something more tangible in the form of a drug or therapeutic procedure.
About Vaclav Seda
Vaclav Seda studied Experimental Animal Biology and Immunology at the Faculty of Science of Masaryk University (MU). Since 2014 he has been working as a junior researcher at the Central European Institute of Technology CEITEC in the research group of Marek Mraz. In 2021, he successfully completed his PhD studies in Experimental Oncology and Cancer Biology at the Faculty of Medicine MU and CEITEC MU. He completed international research fellowships at the Centre Esther Koplowitz in Barcelona and the European Molecular Biology Laboratory (EMBL) in Heidelberg. One year after completing his PhD studies, he already has nine impacted publications, 284 citations and one patent application. In 2021, he was awarded the best presentation at the International CLL Workshop for Young Researchers in Krakow. In 2022 he received the Purkyne Foundation Award for the best publication in the internal field. His hobbies include books, theatre, yoga, long-distance walking, nature and travel.
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