Marek Mraz Discusses the Involvement of Young Haematologists in the EHA

20. Aug. 2019

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We are happy to share the interview in the European Medical Journal with a doctor Marek Mraz, Research Group Leader at CEITEC Masaryk University and member of the YoungEHA (European Hematology Association) Committee. He was interviewed together with two internationally well-known haematologists - Professor Shai Izraeli and Professor Barbara Bain

How does YoungEHA promote the involvement of PhD students and young haematologists in the EHA congress and other important events?

YoungEHA organised a so-called ‘Young EHA tract’ during the EHA Annual congress, which was a series of sessions recommended to young haematologists/scientists. This year, we had several sessions specifically designed to attract and educate young researchers and clinicians. We had a 1-day pre-congress meeting (YoungEHA Research Meeting, Thursday 13th June, 8:45–18:00) that covered numerous interesting topics of basic and translational research in haematology and alternated young speakers and keynote lectures by top senior experts. During the congress, the YoungEHA session (Friday 14th June, 14:30–15:30) covered the different sides of haematology, from discovering a novel drug target to performing clinical trials, and also the processes at regulatory agencies. The second ‘YoungEHA session’ (Sat 15th June, 14:14–17:15) focussed on the future of haematology, personalised therapy, and the use of genomics. YoungEHA also helps to promote the Translational Research Training in Hematology (TRTH) and Clinical Research Training in Hematology (CRTH) classes, and I very much recommend that scientists and haematologists apply for these in the future. Finally, on Saturday night we threw an EHA Grooves party, which was open for everybody but it is definitely a great opportunity to have a good time with young peers.

Personally, what are your roles and responsibilities as a member of the committee, prior to and during the congress?

We rotate our duties each year, and in principle this involves organisation of the sessions that I have described above and giving input to other EHA committees regarding topics such as early-career membership, harmonisation of access to education in different countries, and the identification of future challenges in haematology such as integration of truly personalised medicine via genomic approaches. My responsibility this year was to design together with other members the structure of the YoungEHA sessions and select potential speakers. We also all help to promote the EHA congress, and prepare materials for the EHA press office. This year, several new members are joining the YoungEHA committee, and I will be rotating-off next year.

YoungEHA focusses on inspiring young haematologists and ensuring they reach their full potential; what type of support and opportunities does YoungEHA provide to help young haematologists progress in the field?

The short answer here would be to visit our website: https://ehaweb.org/youngeha/. This will provide useful information regarding all the interesting options for young haematologists and trainees. We have put lot of energy into developing this site in a clear and engaging way. I can mention several opportunities that should not be missed: i) the EHA provides research grants for young scientists and clinicians; ii) the TRTH and CRTH special training and mentoring programs are something that I cannot recommend highly enough; and iii) the Master Class online training platform.

Do you think there are the same opportunities now as there were when you were studying for your PhD or just starting your career in the field? How have things changed?

I think nowadays the science is even more interconnected and thus also more competitive than ever. I left the Czech Republic very early in my career, and I was very lucky that my supervisor and head of the department supported this. I was also lucky when I wanted to return back to Europe after my post-doc in the USA, since I was to be one of the first to receive the EHA Non-Clinical Research grant, which helped me to start my own group. I am not sure that I would have been able to do this without this support. I highly recommend that young researchers use all the training and grant options provided by EHA… They are all well organised and administratively non-demanding.

Nowadays, the mobility options for basic scientists are nearly unlimited, but there are some remaining limitations regarding the transferability of education and clinical training for physician/physician-scientists between different countries, for example between Europe and North America. At least within Europe, this should be addressed in the coming years, including the uncertainty around Brexit. I very much encourage young people to use the opportunity to find a great supervisor and mentor, something that can be done in their home country, but also anywhere in the world.

YoungEHA focusses on inspiring young haematologists and ensuring they reach their full potential; what type of support and opportunities does YoungEHA provide to help young haematologists progress in the field?

I have met some great people to emulate. These include Thomas J. Kipps, who I worked with for several years at the University of California, San Diego; Greg S. Nowakowski and Clive S. Zent from the Mayo Clinic, Minnesota; and Sarka Pospisilova and Jiri Mayer from our University Hospital in Brno, Czech Republic. I guess my style is a mixture of what I learned from these great people. I am trying to push each of my students to their maximal individual potential and acknowledge that each person has some specific talents and weaknesses that can be harnessed and worked on. However, sometimes I joke that the only thing that I can ever really teach them is to be curious and use proper positive and negative controls in their experiments. I also think that persistence and focussed work pays off.

Congratulations on winning the ERC grant from European Commission in 2018 for your research into chronic lymphatic leukaemia (CLL) and B-cell lymphoma! How does this compare to other achievements in your career?

This is extremely important for my lab, and for developing our ideas and research field. We are interested in understanding microenvironmental interactions in chronic lymphocytic leukaemia (CLL) with a special emphasis on the role of non-coding RNA. We have recently showed in several studies that it appears that microRNA are regulating the B cell receptor (BCR) signalling pathway, and that this is deregulated in CLL/lymphomas. This grant allows me to support the lab, and I am looking for enthusiastic post-docs to join this project. It was also followed by multiple invitations to give lectures at conferences and institutes. It is important for the lab, but the only real achievement is the publications and research that my group produce: that is where all our work and passion goes.

Last year, whilst under your supervision, one of your colleagues won a Discovery award. How do you motivate and support young scientists around you to achieve their best?

Gabriela Pavlasova is my PhD student and she published two papers that defined the regulation and molecular function of CD20 in CLL cells. It is paradoxical that anti-CD20 monoclonal antibodies such as rituximab have been used for over 20 years, but the function of CD20 remains unclear. She showed that CLL cells, in the context of immune niches, induce CD20 to boost BCR signalling, and rituximab interferes with this by eliminating cells with the highest levels of CD20 and thus more active BCR signalling. These observations also have implications for therapy, since she described that BCR inhibitor ibrutinib leads to down-modulation of CD20 by interfering with CXCR4 signalling. Practically, this means that ibrutinib is probably not suitable to combine with rituximab, and the Discovery award provided by Novartis acknowledged her for these discoveries.

Gabriela is very hard working, but it also took me about a year to find a project that fits her talents and natural inclinations. Not everything was easy, and I had to put some more time into discussions with her at the beginning of the project. Nowadays however she is very independent and runs multiple projects. It is a serious responsibility of the supervisor to put students on the right path, and it sounds easier than it is sometimes.

Have you observed any areas of research that particularly interest the younger generation of haematologists, or that appear to be an evolving topic of inquiry?

There are so many interesting things, and some of them are obvious in that many people see them, but many things remain unasked because researchers are blinded by the shiny and obvious problems.

My personal impression is that noncoding RNA will be a very fruitful and fascinating area of research, and a lot of young scientists envision this too. There must be a good reason for having >95% of our genome coding RNA that are not translated to proteins….

Young clinicians often also want to take up the challenge of performing a fully personalised therapy in patients. How to do this in a timely fashion, involving the sequencing of gene panels/genomes within days and the quick analysis of big data to make therapeutic decisions is difficult. There is a real need to figure this out. Do we need to combine targeted agents in a fully personalised fashion, and have clinical trials in which each patient receives a unique ‘drug cocktail’?

How has the field of haematology changed since you started your career in research, and what developments are you most excited about for the future?

Everything has changed in last 15 years: we have next-generation sequencing techniques for analysing all layers of regulation; we have genome editing technology such as CRISPR/Cas; we have many newly discovered non-coding RNA; and we have BCR inhibitors developed for B cell leukaemia and lymphomas. I feel privileged to work in a time when we are finally starting to understand some problems in depth, and also witness many new drugs being approved for the benefit of patients.

Finally, do you have any advice to young haematologists who are starting their careers in the field?

The mentoring from supervisors that you receive and determining the scientific area you wish to specialise in is vitally important and is likely to affect your personal life too. Select your mentors carefully. Be ready to fail many times with your experiments (or unfortunately sometimes with your patients), but if you use good positive and negative controls you will always learn something for the next time.

Source: European Medical Journal