Conversations with Lipid Leaders - Aleš Kvasnička, MSc

What is your research and educational background? I obtained my Bachelor's and Master's degrees in Biochemistry at the Faculty of Science, Palacký University Olomouc, Czechia. I am currently finishing my PhD in Clinical Biochemistry and Medicinal Chemistry at the Faculty of Medicine, Palacký University Olomouc, Czechia. I have been working in the field of lipidomics since my Master's studies and my first research project revolved around optimization of untargeted lipidomics of dry blood spots and other microsampling devices. During my PhD, I am investigating various clinical applications of lipidomics in close collaboration with the clinicians at our University Hospital Olomouc in Czechia.

What is your current research focus? At the moment, we are using lipidomics to answer all sorts of clinical research questions. I work in a university hospital where we are trying to translate lipidomics into clinical applications and optimise lipidomics-based tests to meet the needs of laboratory medicine. We are trying to bridge the gap between lipidomics and diagnostic laboratory testing by explaining to clinicians how we can use the information provided by lipidomics and select the relevant markers to answer their clinical questions or problems.

What initially attracted you to study lipidomics? It had to be the challenge in it. The challenge is to understand the new universe of tens of thousands of possible structures of all kinds of lipids and to decipher their role in human health and disease. When I first started reading publications and books on lipidomics, I could hardly comprehend how diverse and vast the world of lipids is. Even after completing my biochemistry degree and having an understanding of lipid biochemistry, I had much more to learn and I still learn new things about lipids every day. I believe that trying to understand the role of lipids in the human organism is a lifelong endeavour, and this makes it a challenge and the main driving force for me.

What has your experience been while using Avanti products? We have very good experience with Avanti products. The most frequently bought consumable is definitely the SPLASH® LIPIDOMIX® which we have spiked as an internal standard to many thousands of samples already. We have also experience with some other mixtures such as SPLASH® II LIPIDOMIX®, EquiSPLASH® and the UltimateSPLASH™ ONE. Additionally, we have bought labelled and unlabeled fatty acids and various ceramide species for other applications. Currently, we are considering to order some unique lipids like long-chain polyunsaturated phosphatidylcholines that would need to be synthesized on request.

What are your biggest motivators to keep up your work? The best part is seeing how our results can directly help patients in our hospital. I can see the untapped potential of lipidomics in clinical applications. We have only scratched the surface of the information that can be obtained from lipidomic profiling of clinical samples. This drives me forward as I see and believe that lipidomics will be used in modern laboratory medicine in the near future and we can already see some of the lipidomics-based tests reaching this stage.

What are your long terms plans within the field? I would like to see several lipidomics-based tests used routinely in hospital laboratories, and we are trying to make that happen. However, I think this will be a collective effort of many laboratories, and we will only be able to realize the potential of clinical lipidomics through collaboration. By that, I mean in particular efforts to standardize and harmonize lipidomics through collaborative ring trials and frequent exchange of experiences. Personally, I would like to see more microsampling applications that provide a new way of communication between the clinical laboratory and the patient through home sampling. Finally, I would like to understand how we can apply epilipidomics and oxylipin analysis in routine laboratory medicine. These are all very challenging topics for the future.

Are there any innovations in the field of lipidomics that excite you about their applications in the future? There are too many actually and I am fascinated by how rapidly the field of lipidomics is advancing. I see it at conferences and publications where a large development can be seen every year. In the terms of clinical applications of lipidomics, there are already a few markers being tested for diagnostic or risk assessment applications in cancer and cardiovascular disease. However, one of the most admirable advancements that are in my opinion ahead of this time is the intraoperative mass spectrometry. The fact that we currently possess the technology to have handheld surgical knives or scanning devices (iKnife or MassSpec Pen) that surgeons can use to distinguish cancerous from normal tissue in real-time seems unreal. The fact that this technology is already in the hands of surgeons and being tested in operating rooms is astonishing.

Where do you see the field in 10 years? In 10 years I believe (and I am willing to bet on it!) that we will have laboratory tests based on LC-MS lipidomics or selected lipidomics-based markers in routine practice. In addition, I expect major advances in processing software using artificial intelligence and machine learning for even more precise lipid identification from mass spectra and advanced data mining. Lipidomics will merge with several other omics and we can already see this happening today. However, I believe that we will be able to extract much more information from our data and integrate it together, leading to an even deeper understanding of the pathobiochemistry of disease at the systems level. In addition, since I love the technology of (not only) mass spectrometers, I am looking forward to the new analyzers, fragmentation mechanisms and imaging technologies that the manufacturers will develop and make available to us.

What are some of your proudest moments you have had while doing your research? My scientific career is just starting, as I am finishing my PhD and am moving on to my next career step at Rikshospitalitet, Oslo, Norway, but there have been several highlights along the way. At the top of this list is definitely my first research article where we investigated lipidome changes caused by hyperuricemia and gout, which was published in Arthritis Research & Therapy (https://doi.org/10.1186/s13075...). Next, my colleagues and I, who were also PhD students, received a doctoral grant ("Comprehensive metabolomic and lipidomic study of tauopathies in transgenic rat models and humans") from our university, which was also a great highlight. I had the opportunity to give oral presentations and promote my research at prestigious international conferences and seminars such as Metabolomics 2024, Lipidomics GRS/GRC 2024, Metabolomics GRS/GRC 2023 and EpiLipidNET meetings. I was also honoured to receive the Avanti Travel Award to attend the Metabolomics 2024. However, what makes me proud is the bigger picture and by that I mean networking and collaboration. I have the honour of being a member of the Early Career Members Network (EMN) Committee of the Metabolomics Society, I was elected as the Chair of the Task Group: Young Scientists of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and finally I am part of the Young Researchers and Investigators Committee of EpiLipidNET. These opportunities have allowed me to be directly involved in shaping the future of these societies and making the voices of young researchers more heard. Finally, I am proud to have successfully supervised 3 bachelor/master students, one of whom even won the Dean's Prize for her thesis.

What advice would you give to people trying to get into lipidomics? Read papers, watch recordings of influential lipidomic scientists (there are many videos freely available on the internet) and become part of international societies. All these factors can help you to get on the track. From my personal experience, I can definitely recommend early career researchers to apply for an internship to some experienced research lab doing lipidomics. I have completed multiple internships during my PhD and each of them provided me with new skills, experience and connections.

What major challenges do you currently face in your research and how do you plan to tackle them? The translation of lipidomics into clinical applications is a winding road due to the lack of standardisation and many other factors, but mainly I think it's sometimes hard to bring clinicians and lipidomic scientists to mutual understanding and some level of compromise. We want to quantify as many lipids as possible in the sample and then want to mine as much information as possible from the data. This information can be quite overwhelming and providing clinicians with complex visualisations and (semi)quantitative values of higher hundreds of lipids can turn their interest off to even continue with lipidomics. So in this regard, we are having a lot of discussions with our clinicians and are working on these compromises.

In what ways do you feel your research will be helpful to the public? I think I already answered this question in a way, but to elaborate further I will be happy and satisfied once my research will directly help to save people's lives and help their wellbeing. We can see it already in our laboratory, where some of my amazing colleagues developed metabolomics-based methods for diagnosis of inherited metabolic disorders (IMD). These methods are routinely used in our lab and have saved many lives of people suffering from IMD. I can see the same for lipidomics not only in the field of IMD but also in other fields such as cardiovascular disease where lipidomics can provide better risk stratification and identify patients at risk which would not be detected by conventional biochemical parameters. We are now trying to establish this method as a routine analysis in our lab and we have successfully analysed samples of more than 3000 CVD patients from our hospital. We are focusing on hyperuricemia and gout patients and how the lipidome is affected by these conditions and how does it respond to treatment. Additionally, we are now testing a lipidomics-based diagnostic model to classify patients with septic inflammation in knee joints compared to chronic inflammation by osteoarthritis. These are some of the projects which will hopefully soon help the patients (not only) in our hospital.

In what ways do you think Avanti could help you with your current research and research in the future? I must say that Avanti has a great and open approach to their customers. Every time, I am talking to some of their representatives there is a constructive discussion regarding their products. I have recently sent Avanti some of my ideas about potential standard mixtures and they offered me to test them and to possibly collaborate. For me it's always a pleasure to discuss the current needs and gaps in lipidomics with the Avanti representatives. I believe that Avanti has played and continues to play a major role in the rapid advancement of the field of lipidomics and I look forward to many new products in the future.

Are they any people you would like to recognize for playing a big part in your success in the field? How did they help you achieve your goals? There are many names to be mentioned as I had a handful of great mentors during my scientific career so far. My lipidomics journey started on my first half-year internship in Tübingen, Germany in the laboratory of Prof. Michael Lämmerhofer. During this visit, I learned the workflow of untargeted SWATH lipidomics under the guidance of my good friend Bernhard Drotleff. This opened the first door for me into the world of lipidomics. Then I had a chance to visit the laboratory of Hiroshi Tsugawa in Japan, where I got my hands on the cutting-edge mass spectrometer ZenoTOF 7600 with EAD fragmentation technology and I helped to test and write tutorial for the MS-DIAL 5 software. Most recently I visited the lab of Prof. Maria Fedorova in Dresden where I familiarized myself with the analytical and computational workflows of oxidized lipid analysis also called epilipidomics. Maria led me to join the EpiLipidNET Cost Action and the YRI committee which provides an inspiring collaborative platform for (epi)lipidomics researchers. There are many more names to be mentioned but most importantly I would like to highlight my PhD supervisor and mentor Prof. David Friedecký. He provided a collaborative and supportive environment to work in, do research and grow. He offered me a lot of freedom to do what I want in my research and helped me in every step when I needed it. I must say that David is a boss with high demands, but also a lot of understanding and an inspirational aura.