ISEV Member eNews - April 2022Member SpotlightAase Handberg Tell us a little about your EV research, what attracted you to this field and what are the biggest obstacles to your EV research? What are your thoughts on how ISEV might help to address any challenges? I was drawn into the EV-research field already in 2009, based on my growing fascination for “the idea of EVs as liquid cellular biopsies” and in that regard, I attended the second ISEV meeting in Gothenburg in 2010. My research is focused on understanding pathophysiology of complications related to obesity and identifying new predictive biomarkers, and as a physician and clinical biochemist with a deep interest in biomarkers specific for cells or tissues I was intrigued by the potential of EVs. Moreover, the information EVs carry has the potential to not only serve as biomarkers for prediction and diagnosis, but also to expand our knowledge and understanding of pathophysiological processes and diseases. This has given me a completely new perspective on physiology and inter-cellular communication and altered my view on pathophysiology as a whole. In my research group, we have focused on high-resolution flow cytometry analysis of EVs due to the magnitude of information gained – phenotypically and quantitatively when measuring EVs directly in plasma, and we have established and refined this methodology in the laboratory over the past years. As I see it, the current obvious challenges in taking EVs from “bench to bedside” are technical in unifying guidelines to ensure quality and compatibility of measurements; however, without setting the standard at a level that keep people from entering the research field all together. My experience with clinical biochemistry has taught me that diagnostic analyses may not be standardized from day one, but eventually converge and undergo international standardization. I see that ISEV can aid in such challenges by establishing and validating calibrators and controls for a range of analysis platforms, which would truly advance EV research and compatibility between groups. Not doing so will prevent EV research from expanding at the pace that meets its clinical potential. What more do you think ISEV could support the global network of EV researchers? I think ISEV could further support the global network by arranging summer schools, courses, and seminars/discussions on guidelines and basic EV research including applied courses. Moreover, reducing participation fees for courses and conferences will further expand the network especially for younger participants. Finally, ISEV should build a platform for sharing ideas and methodology between groups and support such new networks e.g. via an exchange scholarships for younger researchers. Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? Yes, my research group is now primarily focusing on EV research, understanding pathophysiology, and how to improve diagnostics for screening and follow-up on interventions in relation to obesity complications. How do you see your career progressing over the next five to ten years? I will continue to pursue our current research area at Aalborg University Hospital (Aalborg UH) and expand collaborations both locally and internationally to ensure expansion and career development of my research group to prime the next generation of EV researchers to continue our work. In what way have collaborations with other groups or with industry impacted on your EV studies? Collaborations with other groups have made an invaluable impact on my research. In particular, collaborating with Associate Professor Pilar Sepúlveda from the Instituto de Investigación Sanitaria La Fe, Valencia, Spain on the transport and exchange of intra-vesicular lipid content between cells has opened a new and interesting view on the direct functional impact of circulating EVs. In 2020, we established a collaboration with Associate Professor Carlos Salomon from Queensland University Hospital, Australia on the genomic and proteomic content of circulating exosomes in obesity. Moreover, I am hosting Carlos´ visiting professorship at Aalborg UH funded by the Danish Diabetes Academy. Did you go to ISEV2021 or to any other recent meeting in which EV research was discussed and if so, what was a highlight for you? I attended the ISEV as well as the local Danish meeting (DSEV) in 2019. A highlight from the ISEV meeting was an informal discussion with prof. Edith Buzàs on the presence of a protein corona on EVs in plasma, results that were published in JEV, September 2021. Moreover, last year I arranged and hosted a meeting on EVs in complications related to obesity and pregnancy in which Associate Professor Carlos Salomon attended as a keynote speaker. Several disciplines were represented, and this resulted in new and interesting perspectives on EV research. I highly value ISEV and other EV research meetings as I see the possibilities of sharing and combining knowledge and experience with different methods and/or diseases is the optimal way to generate ideas and expand and build collaborations that significantly advance EV research globally. Pia Siljander I discovered platelet “microparticles” during my Ph.D. whilst performing perfusion assays with human blood. My Ph.D. thesis “Platelet collagen interaction and microvesiculation” was born in the era when extracellular vesicles (EVs) were investigated with cell-dedicated flow cytometers and coagulation assays. In the absence of the internet, it was not possible to discover the ubiquitous nature of EVs and the available methodologies were poor regarding the EVs as we now understand them. Thus, I spent a lot of time alone inventing methods for EV quantification; and for my post doc in Cambridge U.K, I abandoned the topic. I returned to the field in 2010 when I discovered that EVs were “everywhere” and also that new technologies were available, eg nanoparticle tracking analysis (NTA). This led to the formation of the EV research group in the University of Helsinki, and since then we have been developing methods culminating in the establishment of the world’s first EV core facility as we boldly called it. Our aim at the EV core has been to make it easier for the newcomers to start, i.e. getting meaningful answers to their EV-research questions, while trying to keep abreast with technologies and standardization. However, despite the immense progress in the EV field, I think that the lack of standardization and insufficient technologies still hamper reproducibility, and are the biggest obstacles holding us back and stopping EV research from gaining its full potential. This is where ISEV and JEV are great and pretty unique as a scientific society and journal – supporting a field that needs to openly discuss the bottlenecks and develop rigor and standardization in its working groups and workshops. By sharing good practices and educating the global network of researchers, we will achieve our goals faster. I will probably be an EV researcher for the rest of my life, because I am at the same time fascinated by the complexity of this ubiquitous cell biological phenomenon and tantalized by its potential in theranostic applications, and we have not yet even started to investigate temporal multicellular communication. I also look forward to the plant and microbe EV research and cross kingdom communication. The possibilities opening with the forthcoming technologies of miniaturized functional assays and single particle characterization will facilitate this. In the biomarker field, I would love to find collaborations where our FastEV (fastev.fi) invention could be tested. I am happy to at the moment have such a great team of ladies in the EV group (https://www2.helsinki.fi/en/researchgroups/extracellular-vesicles) investigating platelet-derived EVs, which never stop surprising us in their multifaceted capacity to generate subpopulations and to be tuned in response to external cues. Currently, we are eager to look at the impact of different platelet EVs in cancer progression. I could state that my fellow EV researchers, the EVians as I like to call them, are the extra spice for me in this research. From the Gothenburg meeting 2011, to the first EU COST Action BM1202, in Finland, the academia-business consortia around EVs have really been inspiring. I love to collaborate because I believe that the most exciting things can only be found where different paths and views cross each other. I have been lucky to participate in many collaborations internationally and nationally; with academics and business. For example, we recently established the Finnish Society of Extracellular Vesicles of which I am the vice-president (fisev.fi). Our research is enabled by my long collaboration with the Finnish Red Cross Blood Service EV researchers for which I am very grateful and hope that our discoveries will one day be useful in practice. Until COVID, I was an avid participant in EV meetings. I have found online meetings such as ISEV 2021 quite useful for learning about novel aspects of EVs. I think a permanent online event could be combined to the onsite ISEV meetings to promote sustainability and equal opportunity. However, the thing online meetings cannot replace is the meeting of fellow EVian minds and chatting till early hours to generate future collaborations.
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