00:00:00:00 - 00:00:35:06 Unknown DNA is basically the book of instructions of our cells, is what directs the behavior of the cell, right? So what I want to understand with this project is how alterations in this book of instructions are also changing the way in which the immune system behaves and in which the immune system can attack or cannot attack malignant cells. 00:00:35:08 - 00:01:08:04 Unknown Welcome to the latest episode of the BBMRI-ERIC Podcast. My name is Mariangela Masiello, media relations specialist here at BBMRI-ERIC. You just heard from Doctor Ángel Alvarez Prado, a principal investigator at the Translational Cancer Immunogenomics Lab at the Luxembourg Institute of Health. This episode profiles Ángel's path from a curious kid and self-described computer nerd to the head of his own lab dedicated to treating cancer. 00:01:08:06 - 00:01:42:17 Unknown Along the way, Ángel found support from BBMRI-ERIC, Ángel first crossed paths with BBMRI-ERIC in 2023 as a postdoctoral fellow at the Ludwig Institute for Cancer Research at the University of Lausanne. He was chosen to participate in the Lindau Nobel Laureate Meeting, an annual event in which young scientists have the rare opportunity to join Nobel Laureates to explore breakthrough in their research field. Research often made possible by biobanks. 00:01:42:19 - 00:02:20:17 Unknown BBMRI-ERIC sponsored Ángel's participation and the event helped spark his motivation to become independent and establish his own translational lab. Later, when the dream of his own lab started to become a reality, Ángel began analysing clinical samples and BBMRI-ERIC was instrumental in identifying suitable collections for his project and streamlining access. In today's episode, Ángel shares his research, his vision for personalised cancer therapies, and offers advice to aspiring scientists considering a career in research. 00:02:20:19 - 00:02:42:14 Unknown Let's meet Ángel and hear about his journey into research. I think this really started a long time ago. I was always very curious about how things work. Also, as a kid, I was always a bit of a computer nerd and I liked to think with computers, you know, to break them open, see the different pieces and understand how the different bits and pieces work together. 00:02:42:16 - 00:03:03:06 Unknown So I think this curiosity really comes from a long time ago. And then, of course, I when I moved to college and I started studying sciences, I couldn't avoid just keeping asking questions, right? So I started to look for internships in different labs. And my first internship was in a lab doing microbiome technology. 00:03:03:06 - 00:03:26:16 Unknown So nothing to do with cancer or immunology, which is what I'm currently working on. But back in the day, I was very curious about how we can really manipulate plant and microorganisms, in that case to improve crop yield. So I’ve always had in my head this idea, and that's why I push it an undergraduate in biotechnology of understanding better biological processes so that we could exploit them to our benefit. 00:03:26:16 - 00:03:51:00 Unknown Right. In this case, getting a better crop deal or producing more food with with less land, or now, as I'm doing in my current research to try to find new treatments for cancer. So, after my undergrad, I started to get more and more interested in immunology and cancer. And that's why for my masters and for my Ph.D., I moved to a full immunology lab. 00:03:51:02 - 00:04:16:00 Unknown What I was mostly focusing on understanding a very fundamental, immune related process, which is also linked to the development of cancer. From then, from my postdoctoral as I stated, it was very clear that they wanted to to integrate both fields. So immunology and cancer. So then I moved to Lausanne to try to see how we could manipulate the immune system to treat cancer, which has been the focus of my research for the last seven/eight years 00:04:16:00 - 00:04:41:10 Unknown and what I'm also doing now in, in my lab. So you you told us that your primary area of focus is cancer. What inspired you to take this direction? So, as I was saying before, I always had this motivation to understand how things work. And later on, when I moved to university, I was interested in also manipulating biological systems, right. 00:04:41:10 - 00:04:57:14 Unknown For our benefit. So it was very clear for me as I was approaching the end of my undergrad studies, that, of course, cancer was a big problem. And at the same time I was enjoying quite a bit immunology. So initially I decided to to go to a lab in which I could do a bit of both right to work in immunology, but also work in cancer. 00:04:57:17 - 00:05:21:04 Unknown So I went to a lab in which they were doing, working on cancers of the immune system, particularly lymphomas, which are solid tumors that arise most frequently from B lymphocytes, the immune cells that are involved in our defenses, but also T lymphocytes, which are also part of this immune system. Now, my research is more focused, as I said before, on manipulating the immune system to treat cancer. 00:05:21:06 - 00:05:42:14 Unknown And I think this really, really started during my phd years when we had a talk fro a very well known tumor microenvironment researcher. And at that moment is when I realised that I was probably being too narrow minded because for my phd, I was just focusing on the carcinogenic process. So how the cancer develops, let's say. 00:05:42:16 - 00:06:03:01 Unknown But I was missing the big picture. And the big picture is that when we think about tumors, there is not only malignant cells. That's what I thought back in the day, that it's only cells that are behaving in a weird way, and that's what we need to attack. But the tumor is a lot more than cancer cells. You have many of the cells, including immune cells that are part of the tumor and which we call the tumor microenvironment. 00:06:03:03 - 00:06:29:15 Unknown So what I learned from this talk, which for me was really revealing, is that this immune microenvironment and this tumor microenvironment is supporting tumor growth, and it's also contributing to therapy failure. But we do know very little about how the immune microenvironment particularly is being hijacked by cancer cells for their benefit. So when I saw this talk, for me, it was immediately clear that for my postdoc, I needed to move from this very concept cell centric view. 00:06:29:19 - 00:06:55:12 Unknown So looking only at the malignant cells towards a more, systems approach, let's say, in which I would look both into cancer cells, but also this microenvironment. And of course, since my background was in immunology and I was always interested in immunology, the most obvious approach to this was to understand how the immune component of the microenvironment is affecting tumor production and responses to therapy, and therefore how we can learn from this to then manipulate it for therapy. 00:06:55:12 - 00:07:27:09 Unknown So I think it was like a step by step progression from genuine curiosity when I was a kid, then jumping into immunology as I advanced in my undergraduate studies, then of course going to the cancer fields for my postdoc, and then as I was approaching the end of my postdoc and trying to decide what to do next with my career, I incorporated this view of the tumor microenvironment in big part thanks to this talk, one of these random events that sometimes happen in life that you don't really expect, but that really changed your career trajectory. 00:07:27:14 - 00:07:49:21 Unknown And I'm very happy I decided to pursue this because at the end, that's where the field is going. And that's where we are seeing more promising results lately. So yeah, I'm really looking forward now to contributing more to the field. Leading my own lab here at the LIH. It's very nice. What were you were saying also about this kind of co link that you had towards research? 00:07:49:21 - 00:08:16:02 Unknown And I have to say that when I was preparing for our interview, I had to look at your curriculum. And it is an impressive curriculum. Could you explain us, speaking about your career, how BBMRI-ERIC has supported you during the different stages of your career? So we first came in touch when I was a postdoc because I was selected for this Nobel Laureate Lindau meeting. 00:08:16:08 - 00:08:40:09 Unknown which is a gathering where they are bringing together like 40/45 Nobel laureates plus people at different stages of their career, scientific career. So you have undergraduate students, you have phd students, you have postdocs and the idea is that you will have an informal gathering with Nobel Prizes to have a free interchange of ideas. So when I was selected for this, my attendance to this event was sponsored by BBMRI-ERIC. 00:08:40:09 - 00:09:01:13 Unknown So this is when I also met the General Director. So this was our first link. They were very nice and very kind to support my attendance to this event, which I think it was really game changing in my career, it was just a once in a lifetime experience. You know, not only being surrounded by all these Nobel Prizes, but also being surrounded by super talented and super motivated scientists at different stages. 00:09:01:13 - 00:09:23:07 Unknown Again, it was really refreshing for me and it kept my motivation really up and going. And then later on, as I was progressing to my postdoc and getting to the end of my postdoc, I of course started to apply to different grants to become independent and to establish my own lab. And when I was putting together one of these grants, of course, I always had in mind, I mentioned it before. 00:09:23:08 - 00:09:44:04 Unknown That's why I started biotechnology, this idea of manipulating biological systems for our benefit, right? And in this case, what I wanted to do in my lab is to have a translational lab. So to be very close to having an impact to patients lives. So all the projects ideas that I was exploring when I started this phase had to do with the study of the analysis of clinical samples. 00:09:44:06 - 00:10:13:16 Unknown So that's when BBMRI-ERIC came again to help and support me, because they helped me identify a large collection of samples that I was planning and that were needed to develop my particular project, which helped us sustain the feasibility of the project and to really give it this translational kick and this translational relevance, because now we are not only modeling the disease in protein systems, we are also looking into patient samples. 00:10:13:18 - 00:10:42:01 Unknown And for this really , BBMRI-ERIC played a critical role and really allowed us to perform this more clinically relevant research. And this brings us to the work you're currently doing at the Luxembourg Institute of Health. And also about the ATTRACT project. Can you tell us more about this project and the role that BBMRI-ERIC played in it? 00:10:42:03 - 00:11:03:00 Unknown So back to the concept that I was talking about earlier. So we have these tumors which are composed of the malignant cells, and then all of the cells in the tumor microenvironment. So the idea behind this project is to understand how variations in DNA. So DNA is basically the book of instructions to our cells is what directs the behavior of the cell. 00:11:03:00 - 00:11:29:20 Unknown Right? So what I want to understand with this project is how alterations in this book of instructions are also changing the way in which the immune system behaves and in which the immune system can attack or cannot attack malignant cells. And the idea here is to do this in the context of metastatic tumors. Why? Because normally the mutations or the alterations in this code of life that we see in these metastatic tumors are the same that we have in the primary cancers. 00:11:29:22 - 00:11:51:23 Unknown So we can understand how these alterations in the book of instructions also shape the behavior of the immune system. We can then come up with new personalised therapies for this very aggressive diseases based only on the mutations of the of the cancers. And that's something that is normally profiled. So when you are diagnosed with a tumor, you normally get this genetic profiling done. 00:11:52:00 - 00:12:14:24 Unknown And then if it happens that you are unlucky and in 20/25 years the tumor spreads to other organs and you have this metastatic disease, then by only knowing the mutations present in the initial tumor, we would be able, if everything works, to predict responses to immunotherapies because we know which the specific changes in the book of instructions correspond to which specific behaviors of the immune system. 00:12:15:00 - 00:12:43:05 Unknown Right. So this is a very ambitious and a very bold idea. But this of course, again, since it has a very key translational component, it requires analysis of large collections of clinical samples, in particular in this case of samples of pre-metastatic tumors. That's the focus of this project. And again, BBMRI was instrumental in identifying suitable collections for this project and making it easier for us to to get access to the samples. 00:12:43:07 - 00:13:16:08 Unknown Thank you for explaining in very simple words what you're looking forward to. So speaking about this, how do you hope your work will impact cancer treatments in the next 5 to 10 years? And is there a specific goals or specific breakthroughs you're working towards? Yeah, I think when when we are talking about scientific research and having an impact on patients lives, I think five, ten years, it really a very short period of time. 00:13:16:08 - 00:13:57:12 Unknown So I'm going to maybe answer to this question more in the long term. Right. Like let's say then or in the next 15, 25 years. And my dream would be, of course, what I mentioned before, to be able to develop personalised therapies for cancers, which currently have a very dismal prognosis. So metastatic cancers based on the genetic makeup of the tumors and of the patients, the idea being, again, that if we can map specific alterations to specific behaviors of the of the immune system, we can then exploit this knowledge to foster immune attack against the tumors, which, at least on paper, should have many advantages as compared to the standard therapy that we have 00:13:57:12 - 00:14:19:16 Unknown nowadays, which is more based on chemo and radiotherapy, which, as you know, are not very specific and have a lot of target effects. So if I could dream, my dream would be that we would produce enough knowledge, for us to be able to develop these personalised therapies by just looking at the book of instructions of the cancer cells and at the book of instructions of different patients, because as you probably know, we are all different. 00:14:19:16 - 00:14:43:18 Unknown So from the moment we are born, we all have different mutations in our DNA. Some of them can be deleterious, some of them can somehow shape the way in which our immune system works. And I think it's critical to understand how this genetic variation that we have crossed talks with the genetic variation that cancer cells acquire as the tumors grow and as they evolve, and how this impacts the immune system. 00:14:43:20 - 00:15:14:07 Unknown And overall, how can we take all this information into account to develop new therapies that would be targeting the immune system, but that would be informed by this genetic information. And then in addition to this, this is one big pilot of the lab, but we are also looking into new ways to overcome immunosuppression in different tumors, because this is also a problem that we observe in many different cancers, that you have immune cells that are part of the tumor, but they are not fighting the cancer as they should, but they are rather helping the cancer. 00:15:14:09 - 00:15:39:02 Unknown And this is what we overall call immunosuppression, right? This ability of the cancer cells to hide from the immune system. So now we have also several projects trying to understand this immunosuppression mechanisms and trying to prevent them. So combined I would say development of personalised therapies that will allow us to to foster antitumoral responses, which is also linked to understanding this immunosuppression and how to prevent it. 00:15:39:04 - 00:16:05:18 Unknown Thank you. This this was really inspiring. And coming back to the bigger picture again. So what advice would you give to young scientists interested in pursuing a career in research? Yeah, this is always a tricky one. I would say stay curious, stay motivated. Have fun, have fun in the lab. Also have fun outside of the lab. I think it's always important. 00:16:05:18 - 00:16:21:13 Unknown It's a very demanding job. So it is very important that you always try to keep this work life balance. But overall, it's important that you're enjoying what you're doing in the lab day to day, right? You need to be curious, you need to be motivated. You need to be having fun and really feeling stimulated by what you're doing every day. 00:16:21:15 - 00:16:40:19 Unknown Then I would have to say that would we usually see a failure, for example, failed experiment that you applied for a grant and you're rejected. Maybe you submit a paper to one of the fancy journals and it doesn't go through. This failure is part of the process. And I think that's also important to to understand, especially when you're starting in this career, that you need to embrace failure. 00:16:40:19 - 00:16:59:08 Unknown Right. This will happen. It happens to everyone, even people who have been extremely successful in their careers. They have faced failure. Many times, you know? So just take it this natural part of the job, you will fail and that's fine. Just learn from it and keep moving. And maybe the last piece of advice would be to be patient, right? 00:16:59:08 - 00:17:17:22 Unknown This is science. We are doing scientific research. This is a long term endeavor. We won't be able to make big findings if we have a short, sighted view. You know, if you're expecting to change the world in 1 or 2 years, I'm sorry. That's not going to happen. So we need to be ambitious, but we need to be ambitious in the long term, you know? 00:17:17:24 - 00:17:40:14 Unknown So I think that will be my three points. Maybe. So stay curious and motivated. Embrace failure as much as you can because that's part of the process. And try to be patient and have more of a long term view rather than a short term. Yeah. Is there is something that we haven't touched in this conversation that you want to add? 00:17:40:16 - 00:18:01:04 Unknown There are so many things we could be talking about right? I think it's always a good moment. And and I would remind that for for anyone and everyone who could be listening to this, to mentioned that we should invest more in science, right? We have extremely talented people, extremely talented people everywhere around the world, and we're wasting a lot of this very valuable talent. 00:18:01:04 - 00:18:23:18 Unknown Yes, because we don't have enough resources. And you see it every day. You know, you see very talented phd students dropping after getting their titles because a postdoc life is too tough or is not well-paid enough or is not stable enough. We see many extremely talented postdocs just dropping because, you know, they don't make it to Pi. So I think we should, first of all, to bring more resources to the table. 00:18:23:18 - 00:18:42:03 Unknown And second, maybe try to restructure a bit the way in which the whole system works. Right? So nowadays it looks like if you're a postdoc and you don't move towards an independent position, towards a PI position who many of us hope, and that was always my goal, but many others don't, and they can still be a great scientist, right? 00:18:42:06 - 00:19:00:16 Unknown But it looks like there is no plan B, it’s that you keep, scaling up, going up the ladder or you are out. So maybe we should think about new ways to find more stable positions in which people, talented people, can keep doing science without necessarily becoming PIs. Also, because the number of pi there can be unlimited, right? 00:19:00:16 - 00:19:20:20 Unknown But we still need to to run the science. And I know of many cases of people who love doing science, one that may be, super motivated to become PIs, but who would love to continue doing research. But they can't because there are not this kind of more permanent or stable positions where they could continue their work. 00:19:20:22 - 00:19:44:06 Unknown So if I could just launch a small shout out to try to bring more funds to the system and maybe be a bit more spreading the way in which we evaluate and in the way in which we try to bring everyone who can really, improve the way in which we do science and probably improve the way in which we make scientific discoveries, which at the end will have an impact. 00:19:44:08 - 00:20:04:15 Unknown Let's make sure that that we won't waste this talent just because we don't have enough funds. So yes, because we are don't have a system that will welcome all of these people. A big thank you to health for taking the time to share its journey and achievements with us. It was great having him on and we can wait to see what he does next. 00:20:04:17 - 00:20:33:11 Unknown BBMRI-ERIC exists to represent and support to the biobanking and biomolecular resources community. To learn more about how we work and read stories from our national notes, visit the BBMRI-ERIC website, which is bbmri-eric.eu and browse the news section. We also regularly share National Node news from across the biobanking community via the BBMRI-ERIC newsletter. 00:20:33:15 - 00:21:04:20 Unknown You can sign up to that on our website. If you enjoyed this podcast, do share it with interested friends and colleagues and leave us a review on whichever platform you listen via. It helps us to reach new listeners. Watch out for our next podcast episode via our BBMRI-ERIC Socials on Twitter, Bluesky and LinkedIn. And thank you for listening.