ISEV Member SpotlightsEach month, ISEV features one or more members in the ISEV Member Spotlight! Check out this month's featured member(s) plus all of the wonderful ISEV members featured in the past. Interested in having the spotlight put on YOU? Email us at [email protected]. 2023 DECEMBER | NOVEMBER | OCTOBER | SEPTEMBER | AUGUST | JULY | JUNE | MAY | APRIL | MARCH | FEBRUARY | JANUARY October Member SpotlightAhmed Abdelgawad
My research focuses on the study of RNA transport in extracellular vesicles (EVs), particularly circular RNAs (circRNAs). I am fortunate to be working on one of the most exciting fields in biological research. EVs have the potential to revolutionize our understanding of the molecular mechanisms of intercellular communication. This potential could be harnessed in developing new diagnostic and therapeutic approaches. The other exciting part of my research involves circRNAs which are a fascinating class of RNAs. CircRNAs are made from the same gene as mRNAs, yet they could exert different, and sometimes even antagonistic, functions such as in cancer. Although, I only started my EVs research quite recently, I was fortunate to be among a wonderful group of researchers who helped me and taught me a lot. Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? ISEV is a wonderful community of researchers and scientists from all around the world that brings opportunities for collaboration both in academic as well as industry settings which further advances EVs research. In addition, ISEV gives researchers a collective voice in advocating the importance and potential of EVresearch and engaging with funding and regulatory agencies. On an individual level, the student network on EVs (SNEV) helps students share their knowledge and address challenges in a supportive environment. As a relatively new member of the EV research community, I think being a part of such network is particularly helpful as I often face many technical questions. This can also help students get in touch with experts which can help them advance their future career. For instance, during the ISEV2023 annual meeting, ISEV organized Meet the Experts lunches where we had a chance to talk to some of the experts in EVs research. In what way have collaborations with other groups or with industry impacted on your EV studies? Collaborations can have a significant impact on advancing our scientific knowledge. As we expand this knowledge, we become more specialized in deeper niches, and hence collaborations are imperative to the continuity of impactful research. We have been collaborating with Ken Witwer’s group at Johns Hopkins University in Baltimore, MD on multiple projects since 2020. We are exploring the role of circular and other non-coding RNAs in EVs in different diseases as well as novel ways to characterize these RNAs in EVs. Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? Yes, there are still many unanswered questions in EVs research that I would like to explore. The two main questions that I am interested in relate to cargo sorting and EVs heterogeneity. Even though a lot of factors involved in cargo sorting have been identified, the mechanistic details of how specific molecules are selectively sorted into EVs are still lacking. It is also fascinating to explore the interplay between cargo sorting and EV heterogeneity. Understanding this process can help improve the therapeutic potential of EVs. We and our collaborators are currently working on addressing some of these questions. What do you think is the most exciting thing in the future of EVs? One of the most exciting directions for future EV research is diagnostics. EVs offer a minimally invasive diagnostic alternative to traditional tissue biopsies. Many biomarker tests have recently completed clinical trials, and so it will be exciting to see some of these biomarkers get approved for clinical trials in the near future. Future therapeutic applications of EVs are also exciting. For example, therapeutic RNAs or proteins could be packaged into EVs that have been engineered to target specific cell types. The non-immunogenicity of EVs, at least from the same species, makes them ideal drug-delivery systems. There are countless therapeutic applications for EVs from the delivery of deficient RNAs or proteins to specific targeting of cancer cells which will help circumvent most of the side effects of chemotherapeutic drugs. How do you see your career progressing over the next five to ten years? I am eager to transition my expertise in EVs into an industrial setting. Working in collaboration with interdisciplinary teams from both academia and industry, I aspire to leverage my knowledge to translate scientific discoveries into practical solutions. I aim to contribute to the development and commercialization of cutting-edge technologies and products based on EVs research. Yuima Sakamoto
We are studying cancer metastasis. Metastasis is established when cancer cells interact with multiple cell types that form a tumor. Our research focuses on EVs, which are one of the communication tools.
Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? I think ISEV provides a good opportunity to get an objective opinion about my results. It is very important to hear from other researchers about my future research activities. In what way have collaborations with other groups or with industry impacted on your EV studies? I believe collaborating is a good stimulus to my research activities and also motivation, and will lead to further EV research development. Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? I would like to investigate whether our results, which demonstrate that inhibition of recipient cell uptake of cancer-derived EVs is associated with reduced metastasis, applies to other types of cancer metastases as well. What do you think is the most exciting thing in the future of EVs? It is my hope that the results of the EV research will help many people to be saved, through the use of multicomponent EV biomarkers to facilitate earlier diagnosis of cancer and other diseases. In addition, to the inhibition of bad EVs to help prevent diseases. How do you see your career progressing over the next five to ten years? I would like to continue my research and be a leader of the team. I would also like to experience research overseas. September Member SpotlightHermine Counil
I am originally from the neuroscience field. When I started my first Master’s internship in a lab in France, I became passionate about investigating Alzheimer’s disease (AD). AD is a complex disease with multiple risks factors such as chronic inflammatory diseases, and its early mechanisms are still unclear. In 2019, I had the opportunity to do an internship in Canada, where I met Prof Charles Ramassamy, who works on several aspects of research involving AD and exosomes. The EV field was new to me, and I was very intrigued by their possible role in AD pathogenesis. I started a PhD in his lab in January 2020. Since then I have been working on the influence of exosomes in the communication between the brain and its periphery, and its putative impact in AD pathogenesis. The COVID-19 pandemic has been the main obstacle to my research progress, but I feel lucky to have been surrounded by my many colleagues. When I started my PhD, I had to learn everything about EVs from scratch. ISEV offers a tremendous amount of guidance, tools, tips and theorical knowledge. I remember watching the videos about what is an exosome and how to do an ultracentrifugation to isolate specific EV sizes. Thanks to the EVClub, I also learned (and still learn) so much about different techniques and new scientific discoveries. Some of the presentations have helped me to plan my research, others to consolidate my results. Nowadays, I spend more time reading and learning about EVs than about neuroscience. ISEV is the biggest society in the EV field and tries to unite researchers from everywhere. It is exciting! I believe that collaborations and mutual aid are the keys for better research and better progress of knowledges. Collaborations with other groups have been beneficial for my research. Either to go further in some experiments, or to contribute another point of view to my project, I enjoy meeting researchers, exchanging, and learning from others. I love learning, so collaborating is something that I would like to continue to expand, and I cannot wait to see what is next!
I definitively would like to continue in the EV and AD research fields, as there is so much more to discover and learn. I am very interested in the influence of EVs on neuronal activity and on neuroinflammation, especially with microglial cells. I would also like to better understand the influence of EVs on brain alterations in metabolic diseases. Even if EVs are not be the cause of AD or other neurodegenerative diseases, there is no doubt that they play an important role in their pathogenesis. EVs can also help us to diagnose these pathologies earlier and to track their progression. I believe that they could also help us to unravel why sporadic AD appears. The EV field is still growing and attracts more and more attention, and there are so many unknowns and unanswered questions, for example, how EVs are taken up in to target cells. To my mind, one of the most exciting things about the future of the EV field is the potential it has to be routinely be used as a biomarker tool for AD and other diseases, such as cancers. How do you see your career progressing over the next five to ten years? After my PhD I would like to do a post-doc and learn new techniques, such as optogenetic. I want to continue in the field of EVs in AD pathogenesis and to understand better what is happening in the brain. Depending on the opportunities, I would enjoy combining this new chapter with travel, but later I wish to establish myself in Canada as a professor. I love sharing knowledge and I would like to teach in a university, while continuing research in my own lab.
Victor Bodart-Santos
I started in the world of EVs 10 years ago during my undergraduate at the Federal University of Rio de Janeiro in Rio de Janeiro, Brazil. At that point, I was studying Mesenchymal Stem Cells (MSCs) therapeutics in CNS disorders and EVs were not as popular. However, the paracrine effect of MSCs alert us about the potential role of EVs as communication agents and their potential for regenerative medicine. Since then, I pursued the role of EVs in different contexts relating to Alzheimer’s disease (AD). In my master's studies, we showed that MSC-EVs are taken up by astroglial cells and protect neurons from synaptic damage. In 2016, during my PhD in Dr. De Felice’s group, I expanded my research to address the pathological involvement of EVs in dementia, and in 2023 we were the first to show that brain-derived EVs from AD and other tauopathies can contribute to memory impairment.
During my EV research, I faced several technical challenges of working in such a young field of study. I believe that ISEV is making good efforts to address many of these challenges through the task forces, MISEV guidelines, and stimulating/supporting the debate among researchers.
Collaboration has been fundamental to my EV research. The study of EVs involves the application of different methodologies, which makes collaborations among research groups with different expertise essential for the advancement of this field. Science becomes easier when you understand that you do not have to be an expert in everything, but instead, you can have the support of others who have already struggled to find good solutions to your question. That is applicable to both research groups and industry and this exchange of knowledge is what keeps science moving forward. I am a neuroscientist and passionate about EVs. Currently, I am working as a post-doctoral researcher in Dr. Tsuneya Ikezu’s group at Mayo Clinic Florida (Jackonsville, US), where we investigate the beneficial and pathological involvement of EVs in neurodegenerative diseases. I strongly believe there is so much to be discovered about EV communication in CNS and neurodegenerative conditions, and these are the core of questions I aim to address in the future. What do you think is the most exciting thing in the future of EVs? I believe EVs have the greatest potential to be used as biomarkers and in therapeutics. I think that in the future new technologies that can combine EVs and synthetic nanoparticles can provide new tools for regenerative medicine, cancer and neurodegenerative disease treatments. In the short to medium term, I intend to answer many of the questions that I still have open as a researcher in academia to then develop my independent career in science, as a principal investigator. In the long term, as part of my mission as a scientist and enthusiast of biotechnology entrepreneurship, I plan to be more involved in the development of scientific-based products that can cross the translational bridge and impact on people's lives.
August Member SpotlightLiam Barry-Carroll
I am currently a post-doc in the NutriNeuro lab in Bordeaux, France, which I began in 2021. I am investigating the profile and changes in EV content during cognitive alteration and how this can be modulated through dietary interventions with omega-3. Finding this project was actually a bit by chance as my research background is in neuroimmunology. Most of the obstacles have been related to establishing a pipeline of EV research in the lab and therefore looking for best practice and protocols to make sure we are really working with EVs.
Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? Over the past year and a half I have had the opportunity to join some very exciting collaborations, which have been a great way to exchange ideas and to improve our protocols and really gives you the chance to look at your research from a different perspective. Yes, I think I would really like to and if I can, to work on building a bridge between EV dynamics and their involvement in neuroimmunology and related CNS disorders. For me it is the fact that we are still really only beginning to understand some of the basic aspects and principles of EV science. In that sense there are still so many open questions and it is very exciting to see how our collective questions unravel in our respective fields. For now, the focus will be on completing my postdoc and then afterwards I am not 100% sure. Ideally, I would like to stay in EV research but I also like to go with the flow so we will see where the rest of my postdoc takes me. Kristine V. Hoagstrom
I am relatively new to the field of EV research and currently in the second year of my Ph.D. program researching EV biogenesis in cancer. I first became interested in the nanoparticle field in the senior year of my undergraduate degree as a method of drug delivery for cancer therapeutics. Upon joining the Hollingsworth lab at UNMC, I found a collaborative group of individuals working on various aspects of EV research in cancer biology. I became particularly fascinated with their unique biogenesis and cargo sorting mechanisms and have since focused my research on furthering our understanding of these processes in cancer. Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? ISEV is a unique professional society that brings together researchers from across the globe to advance the field of EV research. Joining a group such as this, especially as an early-career Ph.D. student, allows me to establish a greater understanding of the ever-growing field and form connections with other EV researchers to share ideas about future studies.
In what way have collaborations with other groups or with industry impacted on your EV studies? As an early-career Ph.D. student, I haven’t had the opportunity to begin many collaborative efforts with other research groups. However, I recently attended my first ISEV annual meeting, ISEV2023, in Seattle, WA, where I found an abundance of opportunities to network and work with other research groups. I anticipate that my collaborative efforts will continue to expand in the coming years, formulating larger-scale research studies that are even more impactful in our EV studies. I look forward to advancing my research and working with colleagues of various expertise and experience levels.
Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? I absolutely plan to continue with EV research in the future! As I’ve mentioned, I’m still extremely new to this research field; therefore, I have a plethora of avenues that I could go down that are fascinating to me. However, my current focus is on EV biogenesis in cancer. As I have a great interest in cancer research, I anticipate future research endeavors will continue to focus on how EVs function in cancer. In particular, I am interested in how the formation of tumor EVs differs from EVs derived from non-cancerous cells. At this point in my career, my research will continue to explore different aspects of EV biogenesis and cargo sorting in cancer, which I anticipate will remain my focus for many years to come.
What do you think is the most exciting thing in the future of EVs? Aside from the research I described above, which concentrates on EV biogenesis in cancer, the other aspect of EV research that I have found particularly exciting is their potential function as a drug delivery system. EVs have so much potential for improving the delivery and effectiveness of cancer treatments, and I look forward to seeing how this develops. One of the reasons I’m currently focused on EV biogenesis in cancer is because having a better understanding of the processes of EV formation and function will aid us in adapting their use in future therapeutics.
How do you see your career progressing over the next five to ten years? For a while now, I have had a great interest in both research and teaching. I enjoy working with students to further their interests and help them advance in whatever path is calling them. Therefore, I definitely see myself in some form of mentorship or teaching role post-graduation. However, I also have a deep passion for research and will want to continue to pursue my unanswered questions during my career. Therefore, post-graduation my goal is to have a healthy balance of teaching and personal research. This will allow me to expand my mind by continuing to ask questions and my students’ minds by introducing them to new ideas. There are so many routes by which I can achieve this, and I am excited to be able to explore them in the coming years of my Ph.D. July Member SpotlightCherie Saffold
I study YRNAs, which are noncoding RNAs that can function to activate toll-like receptors and scaffold proteins together. YRNAs are secreted in EVs, and immune cells can differentially secrete YRNAs during inflammation. I am currently investigating how macrophages package and export YRNAs in EVs. I was attracted to this field because I love learning about how immune cells communicate, and EV communication in the immune system is such an exciting prospect for me. I also like watching this new field blossom from an inside perspective. I’ve attended seminars and conferences where researchers discuss how to define an “extracellular vesicle” whether it be by size, surface marker, or biogenesis pathway. I’ve watched researchers discuss whether particular proteins are packaged into EVs or if certain types of EVs even exist. The EV field is philosophical, unique, and exactly where I want to be.
Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? I joined ISEV so I can connect with EV researchers from around the world. Getting to hear about other members’ research and their perspective on my research helps me be a more rigorous and well-rounded scientist. This year at the ISEV conference, I got to talk to the researcher whose YRNA research is foundational to my thesis project! In what way have collaborations with other groups or with industry impacted on your EV studies? While I am still early in my career, the EV research team at Vanderbilt has been fundamental to my success. Our Center for Extracellular Vesicle Research has shared technologies and resources that I use in my project. We also have seminars and retreats that bring together our EV community so we can share our discoveries and challenges. Do you plan to continue with EV research in the future and if so what questions would you like to pursue? While I don’t know what the future holds for me yet, I want to learn everything there is to know about YRNAs and why they are packaged in EVs. What cells differentially secrete EV-bound YRNA during disease states? What cells receive EV-bound YRNA, and how do EVs affect recipient cells? YRNAs are conserved in all vertebrate mammals, and even exist in bacteria and insects. Why are they so highly conserved? If only I had three more sets of arms. What do you think is the most exciting thing in the future of EVs? The most exciting thing about the future of EVs is the plethora of possibilities for the field. I love talking with my PI and my thesis committee about prospective functions YRNAs may serve inside the cell and as an EV cargo. At Vanderbilt, I have watched my colleagues research the ways in which EVs play a role in cancer, allergic asthma, and cellular stress. Right now, the EV field is ever-changing and full of potential. There is so much left to discover!
How do you see your career progressing over the next 5 to 10 years? While I am still exploring career options, my long-term goal is to be a science communicator. My favorite part about science is discovering new stories to tell. In addition to presenting my own research, I also do some science writing for Vanderbilt’s newspaper and volunteer at Nashville’s science museum. I love getting other people excited about science! So, I want to make my favorite part of science a full-time career. Whether it be through the New York Times or Twitter, I want to communicate science to both expert and non-expert audiences. Shruti Jain
I am currently in the last stages of my PhD research where I have mostly been looking at glycosylation changes in cancer and their use as diagnostic biomarkers within the Biotechnology unit at the University of Turku in Finland. I was introduced to the EV field quite recently when Dr Janne Leivo, a PI in the Early Cancer Diagnostics research group, was also working with EV glycosylations and their potential role in the detection and monitoring of cancer. It is quite exciting to see the remarkable potential of EVs as a non-invasive and accessible source of valuable information about cancer. One of the main obstacles in EV research is the development of standardized methods for isolation, characterization, and analysis. EVs are incredibly diverse in their composition, size, and surface markers, and this heterogeneity poses challenges in establishing robust and reproducible techniques. Additionally, the identification of specific cancer-associated biomarkers within EVs requires extensive validation and verification studies to ensure their clinical utility. We are working towards overcoming these challenges with our technologies and novel assay concepts by combining different biomarker types in a single assay.
Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? ISEV plays a crucial role in facilitating scientific discussions, organizing conferences, and promoting standardized methodologies for EV research. Through these initiatives, ISEV offers a wealth of resources and opportunities for me to stay updated on the latest advancements in the field and contribute to the collective understanding of EVs in cancer biology.
Addressing challenges in cancer biomarker research, such as EV isolation techniques, characterization methods, and validation of biomarkers, can be accomplished through the collaborative efforts and expertise-sharing facilitated by ISEV. The workshops and networking events have been particularly valuable for connecting with other researchers struggling with the same problems. In what way have collaborations with other groups or with industry impacted on your EV studies? Working with other research groups has allowed us access to complementary techniques and technologies that enhance the scope and depth of our EV studies. For example, the Finnish Society of Extracellular Vesicles (FISEV) has helped us to network here in Finland where we have a small but very active community of EV researchers. As our group is situated in the interface of basic and translational research, we collaborate both with clinicians and basic research groups interested in EVs. The clinical experts we work with have been crucial for our research, as validation of new biomarkers requires well-defined and large patient cohorts. The active collaborations with diagnostic industry will also be important to facilitate the transition from bench to bedside by highlighting the potential commercialization and clinical implementation routes for the EV-based technologies. Do you plan to continue with EV research in the future and if so what questions would you like to pursue? I attended my first ISEV annual meeting this year (2023) in Seattle and enjoyed being part of the passionate and vibrant community of EV researchers. If the opportunity presents, I would like to continue and remain a part of this community. EVs have immense potential in revolutionizing cancer diagnosis, prognosis, and treatment monitoring, and there are still numerous intriguing questions that can be pursued. It would be interesting to further explore the role of EV surface markers as potential biomarkers for precise cancer subtyping and stratification. Validating these markers in large patient cohorts and assessing their clinical utility would be crucial steps in translating EV research into the realm of personalized medicine. What do you think is the most exciting thing in the future of EVs? The future of EVs is thrilling due to their potential to transform diagnostics and therapeutics, leading to personalized medicine approaches and significantly improving patient outcomes. Continued research and innovation in the field will undoubtedly bring forth new discoveries and applications, shaping the future of healthcare.
How do you see your career progressing over the next 5 to 10 years? It’s hard to predict where the future leads. I’m currently wrapping up my PhD and preparing for my defence before the end of this year. Meanwhile, I’m also looking for opportunities to pursue after my PhD. I would like to undertake a postdoctoral research position in diagnostics/therapeutics keeping more towards the translational side of research. For my future, I envision a career path that combines academia and industry. April Member SpotlightCRISTINA BAJO
I entered the extracellular vesicle (EV) research field several years ago when Dr. Line, the head of the Cancer Biomarker and Immunotherapy Group, started a new project focussed on prostate cancer-derived EV content, functions and applications. I joined as a PhD student. to research potential RNA EV signatures released by prostate tumor cells that can serve as diagnostic and prognostic biomarkers. Currently, I am working in a more interdisplinary area. Last year I joined the novel Organ-On-Chip in EV group led by Dr. Abols. In collaboration with Cellbox Labs, we are developing new microfluidic devices to isolate EVs with minimal pre-processing. We are also studying EV interactions and communication using different organ-on-chip models. Tell us a little about your EV research, what were some of the challenges and your thoughts on how ISEV might help to address any obstacles to your research? I have been involved in the search for potential EV-RNA biomarkers as prognostic and diagnostic tools for prostate cancer. The biggest obstacle to my EV studies has been EV recovery optimization. My research involved the isolation of EVs from different human biofluids (plasma and urine), which was itself quite challenging since the starting material could be quite scarce. It took some time to optimize and develop the optimal protocol to isolate the maximum amount of EV RNA from the samples. Recently, I have been involved in developing a new microfluidic device using bifurcated asymmetric field flow fractionation, which allows the isolation of EVs in a gentle and efficient manner from large volumes of each sample with minimal or no pre-processing. The main challenge, has been developing the chip to isolate specific EV subpopulations. ISEV has dedicated task forces for both urine and plasma, and they are preparing to publish revised MISEV guidelines. I am optimistic that these updates will help address the issues that myself and others face. What more do you think ISEV could support the global network of EV researchers? I believe that ISEV has great potential, and the work done by the education team and task forces is truly commendable. In my opinion, the ISEV community would benefit from specific short-term mobility grants for PhD/early career scientists, allowing exchange between different EV labs. Additionally, it would be a good idea to have a Young/Early Career Conference or a session at the Annual ISEV Meeting, where young researchers can showcase their work and receive advice from renowned scientist in the field. It would also be helpful to have a platform directly related to ISEV, such as a forum, where researchers can share ideas or experiences related to EV issues. Having a journal section where researchers can publish or discuss negative results regarding EV topics would also be valuable. In my opinión, these actions would strenghten the ISEV community, increase collaboration between labs, and promote research. Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? In one word, yes. Research on EVs has been a rapidly growing area in recent years, with the potential to revolutionize our understanding of cellular communication and disease pathogenesis. So, in the future, we would like to explore how immune system-released EVs affect cancer and the microbiome using organ-on-chips models. This approach provides a platform to investigate the dynamic interplay between immune cells, cancer cells, and the microbiome, enabling key mediators and pathways involved in disease progression to be identified. Understanding the role of EVs in these processes may lead to the development of novel therapeutic approaches that target specific EV-mediated pathways to improve cancer outcomes or maintain a healthy microbiome. How do you see your career progressing over the next five to ten years? I am uncertain about what future holds, but I envision pursuing a career including both research and education. I am primarly focussed on research, but I also believe it is important to contribute to society by educating future generations, so they can continue to learn and make progress. In what way have collaborations with other groups or with industry impacted on your EV studies? Unfortunately, I was unable to attend ISEV2022. However, I did attend the Blood EV workshop held in Helsinki last September, which was an excellent experience. The open-discussion format allowed individuals at any stage in their career to discuss their main concerns regarding blood EVs and collaborate on solutions. March 2023 Member SpotlightCharles Lai
During my PhD, I studied gap junction-mediated intercellular communications, which fascinated me as a relatively direct and intuitive mechanism. Since 2010, I have studied EVs as another form of cell-to-cell communication during postdoctoral training in Dr. Xandra Breakefield’s group at Massachusetts General Hospital and Harvard Medical School in Boston, USA. It has since been an exciting journey, as the implications of EV research have extended into almost every biological field imaginable.
My research is curiosity-driven, but always relates to real world applications. In the early days of EV research, many of us began with EV isolation by differential centrifugation followed by nucleic acid extraction to understand their contents; EV purification and characterization methods have since expanded significantly. As critical EV-RNA findings were being made, I became curious as to how nanosized EVs circulate within organisms: where and how do EVs travel to exert biological function(s)? More than a decade later, my research continues to focus on answering these important questions.
During my postdoctoral research fellowship, I developed one of the first EV imaging reporters for subcellular (PalmGFP and PalmtdTomato) and whole animal (GlucB) EV tracking. My first research group developed the first bioluminescence resonance energy transfer EV reporter (PalmGRET) in 2015, which enabled multi-resolution tracking from living animals to individual cells. Concurrently, my team and I employed established PalmGRET to elucidate organotropism and the dynamic biodistribution of tumor EVs at the level of organ systems. More recently, we found that malignant breast cancer cells release both big (>200 nm diameter) and small (<200 nm) EVs with distinct biodistribution profiles while individually promoting tumor growth in vivo. We also openly shared EV reporters (mostly via Addgene), and are fortunate to collaborate and apply them with many labs from around the world; I have met many such groups at ISEV meetings, starting from the very first ISEV annual conference in Gothenburg, Sweden in 2012!
EV research is both fun and challenging as it relies on partnerships between scientists in multiple disciplines, ranging from biology and chemistry to engineering. A typical EV study involves multiple protocols, including cell culture, EV isolation, characterization, detection and defining terminology – each of which demands precise experimental design while each aspect continues to be optimized and updated. In other words, EV study is context-dependent and not at all straightforward, as there is no single perfect EV study protocol; indeed, this remains one of the main challenges in EV research. ISEV plays a pivotal role in helping solve this conundrum by facilitating international and domestic conferences for researchers to share and discuss their latest findings (and mistakes), as well as by publishing position papers to serve as general guidelines. We’ve only just begun to appreciate the intricacy of EV-mediated communication, and I am dedicated to helping to resolve the complex EV networks in living organisms.
Dr. Charles Lai is currently an Associate Research Fellow at the Institute of Atomic and Molecular Sciences, Academia Sinica, Taiwan. Prior to this, he was an Assistant Professor at the National Tsing Hua University in Taiwan, an Instructor at Harvard Medical School, and an Assistant in Neuroscience at Massachusetts General Hospital, USA.
February 2023 Member SpotlightDr. Wanessa Fernanda Altei
I discovered the EV field when I started my postdoc. On that occasion my work involved the isolation and characterization of EVs from triple-negative cancer cells, to further apply them to functional studies in vitro. Specifically, I have investigated the role of the adhesion receptor integrin αvβ3 on EVs. Currently, I work at Barretos Cancer Hospital (Sao Paulo – Brazil) as an associate researcher. I am interested to investigate the role of EVs in cell communication after radiotherapy by analyzing blood-derived EVs isolated from cancer patients, and also by in vitro studies. Considering the exponential development of radiotherapy techniques and machines in the last decades, our main interest is to investigate different radiobiological responses after different dose schemes, considering modern treatment approaches. The study of blood-derived EVs is challenging, because of the complex composition of blood, and the high number of non-EV components that we can co-isolate. The ISEV talks and discussions have helped me in the last months to get information about some important issues that I have faced in the last couple of years. My expectations for the future would be the expansion of EVs studies in Latin America, in a way that EV researchers from this area could be more visible in big events in the field. In my opinion, EV research is an extraordinary field and brings great opportunities despite the challenges. I see great potential for EVs as biomarkers for diagnosis and treatment responses, besides the whole range of drug delivery systems that are a possibility by employing EV engineering. I am starting to develop my research group focused on radiobiology studies, and in the next five to ten years my goal is to understand whether EVs are important players in radiotherapy, building on the work of researchers in recent papers. Collaborations are fundamental requirement ofithis field, mainly because of the challenges of using appropriate techniques for EV studies. Considering the expensive infrastructure involved, and the high demand for equipment, from image acquisition systems to nano analyzers, I see collaborations as a key way way to make comprehensive investigations. I did not go to ISEV2022, and unfortunately, I could not participate in any big event in the area in 2022, but I followed some discussion points such as the classification and nomenclature of EVs and the new MISEV. Maja KosanovicHow did you become interested in the EV field and begin to incorporate it into your research? I first came across EVs when I was sent to the “wrong” meeting in 2011! As a young scientist I worked on glycosylation of tumor markers and we had a small collaboration with colleagues who were members of the COST Action focusing on urinary proteomics. They invited me to one of the actions’ meetings. Since our main research did not involve either proteomics nor urine per se (only one tumor marker in urine), I always joke that it was a “wrong” meeting. However, that meeting turned out to be a decisive moment of my career. There, in the basement meeting room of the Hotel Melia Castilla in Madrid, I first heard about EVs and immediately noticed there were many questions - and almost no answers. So, I figured, this must be something very interesting! Upon returning, it took me almost three months to persuade my, now former, boss to let me try to isolate EVs – but once I started the research, I couldn’t help falling in love with the field.
Can you tell us a little about your EV research, some of the challenges and your thoughts on how ISEV might help to address any obstacles to your research? In the last 11 years I have come a long way from trying to overcome contamination issues in the isolation of urinary and amniotic fluid EVs, resulting in the introduction of methods, such as Tam-Horsfall protein (THP) precipitation and ion-exchange chromatography to EVs research, through their glyco-characterization, to what is now my main topic: investigating inter-kingdom communication by EVs and exploring helminths’ EVs immunomodulatory potential as a basis of novel therapies. However, there is a long way to go to reach our aim of EV-based therapy. As the most prominent challenges, not only for our research, I see two issues: first, defining the exact mechanism of action of EVs, i.e. identification of active molecules in the vast complexity of EVs (comprising both heterogeneity and composition), which will most probably turn out to be a combination of molecules, and second, targeting therapeutic EVs to enhance their effect and decrease unwanted interactions.
What more do you think ISEV could do to support the global network of EV researchers? I believe the community of EVs researchers would benefit from more open discussions on the topic of gaps in the field and possible ways forward, whether during ISEV annual conferences (which should be shared beyond on-site participants) or on some other platform.
Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? Yes, of course! Being a witness of how the EV field grew in the last decade, both in the knowledge about EV biology and in development of fascinating new techniques, and also being aware of so many inspiring challenges and potentials ahead, my initial fascination with EVs grew stronger along the way and now I see myself exclusively as an EVs researcher. It also led me to now be the first president of the Serbian Society for Extracellular Vesicles, SrbEVs. Thus, I believe EVs will be my research interests till the day I retire. Although my EV focus might change in the future, at this point, the most interesting line of our research that lays ahead is trying to define active molecules in helminths’ EVs. The next big task, not just for our research but globally, I believe, would be targeting therapeutic EVs, whether natural or artificial ones. I think this step is a crucial to the wide clinical application of EVs. In what way have collaborations with other groups or with industry impacted on your EV studies? I strongly believe that collaborations provide unsurpassed opportunity not only to work on the same topic, share samples, techniques and model systems, but even more valuable, to exchange, in an open manner, ideas, opinions and visions with colleagues who inevitably become your friends, and to become enriched and grow from the exchange of cultures, both in the workplace and more generally. ISEV, along with the COST Action European Network on Microvesicle and Exosomes in Health and Disease (ME-HaD) played an immense role in providing me with the opportunity to get to know many colleagues in the field, so today I have collaborations with some of the most prominent EV researchers and the opportunity to work on exciting challenges.
Did you go to ISEV2022 or to any other recent meeting in which EV research was discussed and if so, was there a particular highlight for you? I attended the last ISEV meeting in Lyon, in 2022 and had a wonderful time. Apart from many interesting insights, after missing a couple of ISEV annual meetings due to the pandemic and other reasons, meeting all these dear people in person again was the highlight of the meeting for me. As a “cherry on top”, my illustration of “renal proximal tubular epithelial cells as targets for therapeutic EVs” was elected the best in the category of interpretative images from seniors, which was very nice, since scientific illustration is a hobby of mine.
January 2023 Member SpotlightLisette Retana Moreira
After this enriching experience, I incorporated my new knowledge into my job at the University of Costa Rica and started a new line of investigation into EVs secreted by parasites, which is one of the strongest fields of research in our group nowadays. Tell us a little about your EV research, what were some of the challenges and your thoughts on how ISEV might help to address any obstacles to your research? During our work we have faced some important challenges, mostly related to starting a new line of research and all of the standardization procedures that were necessary, which was performed during the CoVID-19 pandemic. Of course, I can`t forget to mention the intrinsic challenges of working with EVs! What more do you think ISEV could support the global network of EV researchers?
Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? As a microbiologist specializing in parasites, I would like to continue working on EVs secreted by these organisms and the possibility of employing them as biomarkers of disease, to try develop rapid and accurate diagnostic tools. I started my EV journey with Trypanosoma cruzi, continued with Acanthamoeba and Naegleria fowleri and I am now collaborating in the isolation and characterization of EVs from different Plasmodium species and different cell lines. There are so many applications and interesting topics in the EV field that I wish to continue my career in this line and get more experience that I could share with students and other researchers.
December 2022 Member SpotlightVivian Nguyen
It is fascinating to me that EVs can be secreted by all cell types. Once secreted, EVs then travel and communicate with nearby or distant cells, and actively influence local processes. Despite an explosion of interest in EVs, many fundamental insights into their biological functions are still lacking. The importance of the release of cargo into the extracellular environment is recognized. But still, the knowledge and application of EV in medical research are uncertain. Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? In what way have collaborations with other groups or with industry impacted on your EV studies? Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? What do you think is the most exciting thing in the future of EVs? November 2022 Member SpotlightAida Hansen
Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? In what way have collaborations with other groups or with industry impacted on your EV studies? Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? What do you think is the most exciting thing in the future of EVs? Dima Ter-Ovanesyan
In terms of obstacles, there were many obstacles… The field of EVs is a young field even today, but was even more so when I started. This is exciting, and one of the things that drew me to the field, because there are many questions that are wide open. But this is also frustrating, because you have to often start from scratch and develop new tools or frameworks for studying EVs, since even basic questions (how do we measure EVs?) are not established. Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? I joined ISEV after attending the International Workshop on Exosomes at the Institut Curie in Paris in 2011. It was at this meeting that Jan Lotvall and others proposed starting ISEV. I think I am one of the few people who then attended the first ISEV conference in Gothenburg in 2012 and all of the subsequent ISEV meetings since then. If only there was a perfect attendance award… The annual ISEV conference is the biggest EV meeting, so it has been very useful for keeping up with the field. I’ve also met many great people at ISEV conferences that have become friends and collaborators. In what way have collaborations with other groups or with industry impacted on your EV studies? Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? What do you think is the most exciting thing in the future of EVs? October 2022 Member SpotlightBarbara Adem
Why did you join ISEV and what are your thoughts on how ISEV might help you to address any challenges? Do you plan to continue with EV research in the future and if so, what questions would you like to pursue? What do you think is the most exciting thing in the future of EVs?
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