Welcome to the Proteomics in Proximity podcast, where your co hosts Dale Yuzuki, Cindy Lawley and Sarantis Chlamydis from OLink Proteomics talk about the intersection of Proteomics with genomics for drug target discovery to the application of proteomics to reveal disease biomarkers and current trends in using proteomics to unlock biological mechanisms. Here we have your hosts, Dale, Cindy, and Saranits hello everybody. Uh, I'm happy to welcome you in another episode from Proteomics in Proximity, together with um, my cohost Dale and Cindy. We are really happy today to have with us Ida Grunberg, the Chief Scientific Officer of Olink. Really happy to discuss with her about her career and uh, ongoing projects and ongoing outcomes in uh, Olink. Welcome Ida. Uh, thank you very much. Thanks for having me. Great to meet you can join us. Thank you very much Ida, for joining. Actually, I will start the question by I would like to know a little bit more about your background and what was your status and how do you see your transition from academic to the industry? Can you share a little bit more of your experience? It would be really nice to hear. Of course, I don't know how much time we have, but I try to keep it short. So I'm a molecular biologist by training. And then I joined professor of Landergren's group to start my PhD. And at the time I joined, he had actually just founded Olink. So they were just the floor above us. Uh, so I was very early introduced to OLink, but uh, it was a great group to spend a PhD in. Very uh, inspiring and creative. We were developing all different molecular tools targeting DNA, RNA and protein, depending on the research question. So I think that thanks to my time there, I got a great foundation, um, and a very open mind to the importance of all the omics. Ida, I'm curious what years roughly, I mean, not to date yourself, but was it the early 2000s, late 1990s? It was the I joined Ulf's (Ulf Landegren's) Lab in January 2006, and they had founded Olink in late on board, I think in was there between 2006 and And then I focused actually more, sorry to say, not on proteins, but on the transcriptomic side. So I was working more with Professor Mats Nilsson's group, developing uh, technology for transcript detection, more for point mutation and genotyping applications for colorectal cancer and lung cancer applications. So it was actually I'm sorry, was this using sequencing? No, it was an in-situ-based application. Uh, so we were using padlock probe that had been invented in Ulf's and Mat's group. So there was a microscope, ... readout. So really like padlock probes similar to molecular inversion. Exactly. Halo Genomics, yeah, they were all in the family. So again, we were almost fantastic group to be very privileged to have done my PhD there. So it was during my last year where actually the technology I have been working on developing that we licensed that together with Olink. So that was my door into the company. So uh, just after I finished my PhD, I continued at R&D, at Olink and first focused on continue commercializing that technology that was later sold off to another company and I continued that R&D, working more on the technologies that... we are focusing on now, more on the proximity extension assay. That was also around the time when we first launched the first panel. So that a lot of things were happening and still keep in mind that that was the early days. So I don't know, maybe we're 25 people, more than half of the company were at R&D. But then of course we had commercialization going. so then I was recruited to the small commercial team at the time, um, first I had been in academia, so for me it was like, wow, uh, transition, should I go into sales? But at that time we had zero customers, one product coming out. So it was really, from the beginning, a very scientific sell working with our collaborators, close friends, in Uppsala. So I think we were three people at the commercial team at the time. So I didn't see it as a scary transition actually. But I always think... Help me with. The date, help me with the dates. Now is this So still very early days. So the first now we call it Target 96 oncology was launched in years uh, covering the Nordic and European and then 2015 we had decided that the biggest market is in the US. We need to have someone being based there. So I was asked if I could go over and start off our US market. So that's when I did the move to Boston. That must have been such an interesting transition for you to start something in the US. Where... no recognition of the technology, no friends, no colleagues, maybe a few colleagues. Yeah. How was that? How was that? No, you're right, it was extremely exciting, but also extremely scary, but a... very valuable experience. But as you said, I had zero colleagues in the US. I moved to Boston by myself. I had been there once before for like a day, so I knew basically no one. And since we didn't have anything in place, really, we had to start from scratch. But took day by day and first settling in at an incubator in Cambridge and started connecting with the amazing few customers we had at the time and went from there. What was one of the most influential customers at that time? Is there someone you can point to or a couple of them that really opened your eyes to how the technology could change things? Yeah. No, but for sure, I mean, we were very lucky to, for example, working with The Broad from really the beginning. So the incubator, that I was working from was basically in the same block as The Broad. So definitely there I spent some time and trying to get in and set up some seminars and so on. ...We had some there and also at the MGH (Massachusetts General Hospital), we had some early adopters there as well. So I tried to stick very close to them. so that was really the beginning. And also why we decided to set up in Boston, Cambridge. That is the Mecca of life science, but also where we have the early adopters. Yeah, not a bad neighborhood to hang out in. Right next door to The Broad, just down the street from MGH, actually. I remember like, walking down Broadway and I felt my IQ was just raising. That was a good spot. Would you remember any of the first projects that you have been involved? Let's say the first favorite one. You mean from the US market? Yes, from the US market. One of the first that you had close to your heart, actually. For sure. Since we basically no one knew about us, uh, we had to have some strategies on how are we going to actually generate some evidence and content. Because already back then, we believed in it's. Not enough just us showing what was the power, the power of the technology, but generating real data. So we hooked up with, some researchers at Stanford then in San Diego. So with Stanford, ah, we had more of a wellness study where we were comparing different diets that, the different group of peoples were on. So we could track the effect of inflammation if you're on a high fat or low carb diet. So that was one of these case studies that we early did. Another one was done in San Diego with Professor Doug Galasko where he had a study on the effect of antioxidants on Alzheimer's disease. So there we also did a study together with him so we could generate great, data that we could go out and have joint road shows with. I mean, from your work in the in situ transcript- omics now to Alzheimer's and wellness. Right. What a shift. A huge shift, right? What early days to be looking at wellness, right? This is such a hot topic. Right? Isn't that amazing? Yeah, exactly. I don't know if it was just luck, but those early studies have still been shown to be very modern and been very active in the spaces as well now. So luck maybe Doug and Doug is. Still leading the way. Or the Alzheimer's... arena, for sure. Yeah, exactly. So remarkable. But we have also, I think all of you have heard about us. That could be a nice story as well. So again, since coming to the US. And basically no one knew about Olink and this little small Swedish company. but, ... for being such a small country, there's a lot of great researchers and scientists in the States. So we try to also work very closely with them. We formed what we called the Swedish Mafia so we could all yeah. ...we didn't say it... To be clear, this is not the "Swedish House Mafia." That's a music thing. No, but seriously, so it was great. So we have that at Stanford, then in Rockefeller, and teamed up with them. And then they were also happy to support and really put Sweden on the map there. And... we have for sure, a good reputation, especially in protein history. So we try to also leverage on that and not just saying with this unknown Swedish company, but we're proud and we're here for a reason, because we know this. And as far as in the early days, people were sending samples. Right. You were getting customers sending samples to Uppsala. But then shortly after right. Didn't you start actually building a laboratory here? No, exactly. So I moved in 2015. Then, just a few months after, we started to have these studies coming in. And some of them were critical to have them run in the States. So then, of course, we wanted an office in Boston, but we realized we also need a lab. So that's when we started to look for different places. So my role was very broad, going around, looking at different spaces. And then we found this beautiful old garage in Watertown, literally a garage. Show you a picture. It was going to be rebuilt into a small lab space. So that's where we started. And... the rest is history. And we always thought this garage story was great and used to say that, well, Apple started in the garage too. Wow. This particular garage. Then you installed a BioMark. Right? And I understand an employee, Dan Frederick of ours, who's an application scientist, he told me a little bit about that first installation. What can you tell me about it? I don't know any details. It was two or one. Uh, we did, but the space was so tight, so it was funny. We grew out of that mobile garage in no time, and especially when we were going to have two BioMarKs. And I can't remember I think we even had three there. And these are big pieces. Very big. In the end, we were having meetings in the cars outside because we couldn't fit in there. The cars "...meet me in my car!" We're doing a podcast. Right. That's an interesting. Dan told the story of how it grew so quickly. And then, of course, when the opportunity came for him to work for Olink, it was a very easy decision for him to make, just witnessing firsthand that kind of growth. And, these customers then you had to hire, I guess you then hired people to run the laboratory assays, that kind of thing you were central to that. Yeah, for sure. So one of the first employees was Jen, who is still working with us. She's great. So she's been there from the beginning and many others as well. So many times we get nostalgic and remembers the garage. Yeah. And I think also, together with all that growth, the need of people to use proteomics, right. You see this change of people of thinking from one publication to thousand publications, right? How do you see this? How do you see this, actually? How was your feeling for the first publication when it came out? Can you describe? It was that huge. We used to have like a bell, so we're walking in the corridors like, wow, it was big. It was big. And especially, I mean, looking back, the first paper that was in Nature Communications, our close collaborator, Professor Ulf Gyllensten, it was a great paper. I mean, looking back, it was only one panel of 92 proteins, but a big study. So fascinating outcome that really paved the way to where we are today. So, yeah. For those who may not be familiar, right, this paper did over a thousand Swedish individuals. So they had genotyping data and then they looked at to protein. Then they had health outcome data and then they had all the clinical data. So they can talk about the influence of genetics upon the biomarkers, genetics upon the outcomes, and then the other lifestyle and clinical factors. I mean, reading it now, I mean, it was a 2014 paper and it was like, wow. Exactly the fascinating chord of it. So it's a population study from the very far north of Sweden, Karesuando, where it's like freezing year round. And they had been following these thousand individuals for a long time and as you said, had all the information on their lifestyle and diets, but they wanted to add proteomics to it. And then, I mean, still less than hundred proteins, but uh, they could gain so much data and insight from, uh, these results quickly. Their conclusion, or the take home from the study was that they could really see the effect of non-disease factors. So this was a healthy population, but still see that. I think more than varying. All the variance were actually coming from these genetic and lifestyle factors. So like age and blood pressure and weight and smoking habits, all of that had an enormous effect... on proteins. And they mapped all of that. It was just demonstrating that value of capturing real time biology in the context of the genetics. It's a phenomenal paper. Yeah, for sure. And also it was a very broad paper that they could also follow up. They called it like a publication generator, the data that they get out because then they could also follow up and see. So what should we do with all this information? Is there any way that we can associate these results to more actionable, diagnostical, clinical, biomarkers? In the follow up paper, they proposed... a model to adjust for these... variables and that algorithm that they proposed back then is very relevant today. That they find really select the most robust biomarkers that are not varying because of these non-disease factors. So a great start of the thousand papers. It sort of reminds me a little bit of I'm sorry to make the parallel to the sequencing space but that's sort of sequence once query often, right? You have such a broad look at proteins that you can deep dive into those data for multiple different purposes across that population. Just at that time that was very high-plex, we call that midplex now. But that's a beautiful ... point... about the data set. And what was also really interesting for me was this idea of clinical cut off. Exactly. In that you have sort of individuals, right, with certain levels of certain biomarkers and if you have a certain one or a handful that spike up or drop off, that means something is happening, right, health wise for that individual. So here we're talking about personalized medicine based upon the individual's protein profile at a given time and their genetic background and of course their lifestyle and the different things that they do. I was thinking "this is personalized medicine, this is the future", right? It's in reference to the population that you're able to compare it to. And today we're seeing such diverse populations being characterized with proteomics. So it's an exciting time there as well, right? But we started somewhere and that ability to be personalized and translate to the impact genetics is having on something that we might actually take to the clinic. Maybe not Olink, but those customers is exciting. Mhm, this particular population in the far north of Sweden is still being followed then today? I don't think they have additional samples taken as far as I know. But they continued studying that and then also since that was the first more epidemiology study we did, they also were part of a European network with other concerned populations that followed. So that was really the start uh, of it. And also with all these lifestyle factors they had many more papers coming where they were looking into the specific factors affecting like the Swedish tobacco with the snuff for example. That they saw association to some biomarkers and they got some media attention for also using that to look at aging and biological versus chronological aging and how diets like fish and coffee can affect or reduce your aging and so on. So... it was fascinating. that's great news for us. Coffee drinkers for sure. Yeah, exactly. Well I think on the reference to snuff for those not familiar with it. It's really popular in Sweden, I guess most of Europe, but I think it hasn't hit the US yet. Is it popular in Greece? It's kind of a thing you put in your gum. And is it nicotine? Yes, for sure. No, it's actually not even all of Nordic, but some of the Nordic countries, but yes, that's why also this type of research was supported. I would say it's very popular in some areas of the US as well. For sure. Okay, so you've seen it here. Absolutely. This cohort is like it was really well conserved. An isolated cohort. Right. They've seen the real effects and the real association with the biomarkers without any so much external air pollution or other factor they may influence with that. That was a beautiful place, actually. It was a beautiful, amazing yes, exactly. It's hard to capture those environmental variables right. But that the protein levels could exceed the challenges with capturing some environmental variables. I think that's a message that I find we have to convey to a lot of geneticists who are used to the signals being weaker and harder to see, ... and having the power to detect some of these polygenic signals... to disease can be more challenging in genetic studies that are solely genetics and disease. But I think bringing in proteins can allow for magnification of that ability to see that association. Mhm yeah. So then back to that. This was the first publication, I don't think we could have asked for a better start because it really first, I mean, demonstrated the robustness of the technology that was very important being new into the market, but also the power, as Cindy said, combining high quality proteomics with genetics and this epidemiological information. And now 1000 publications later, I understand the same group had a very interesting recent Olink publication as well. What can you share about that? Yeah, I mean they have since the beginning. So they started more with population, health studies and then part of one of the course they did, they saw some interesting signatures for gynecological cancers. So then they continued drilling down that path and then saw early an interesting signature, for patient statification of ovarian cancer. So we worked with them around that and together with this group that we also begin our journey with our focus panel with custom development. So we helped out with developing that protocol with the input from FDA and that whole story. I was just going to say I also love that Stefan Enroth, who was the first author on that early paper, is now the PI (principal investigator), the last author in this most recent paper. We all evolve. Yeah. No exactly. So they have continued I mean, we developed a focused signature panel for ovarian cancer where they could see that they were superior to what is actually used today in diagnostics, in the US. But they have continued trying to polish on that and hoping to get it to something clinically,useful. And also looked into other matrices. So this was first based on plasma, but also looking into alternative matrices that can be, sampled in a home environment with filter papers. And now, using our (Olink) Explore, the broadest .ibrary. So that was a paper that came out, just was it last week or two weeks ago, where they now have continued to really polish on this signature. So great work. And for background, ovarian cancer, third major fatality rate, not very good biomarkers at all. CA ages, it's just not that great. You mentioned patient stratification. So this particular Focus and what you're talking about is a custom product of they applied a handful of markers. Was that to stratify patients for treatment? So the first question was more for patient stratification because many women are having surgery without needing it, basically. So that was the first where they wanted to stratify women with benign cysts from ovarian cancer, Like a blood test to stratify those. So that's where they started, but now going into more diagnostic applications for basically early diagnostic of to identify those early stages. Yes. So is this also for recurrence monitoring? Yes. So that's a huge application right. Where women will have a cyst removed, like you mentioned, but they don't know when they need to go ahead. And there's really no real good way to measure when it's coming back. And so it's like living underneath this constant fear of recurring, right, ovarian cancer, which is a huge medical burden, for sure. And especially if we can come to the point where we could have for more careful monitoring of those in high risk. Yeah, I love that it's in women's health as well, which we talk about being an area that could use some more funding. Right? Yeah. And you mentioned then about Explorer and perhaps alternative matrices, that kind of thing. Right. I mean that has must been... from that start with the early work with 92 Plex, assays now to time. I'm curious, you mentioned alternative matrices. What were some of the more unusual things you've seen in terms of in all these years ways people are measuring proteins? Yeah, I think we have covered the whole human body, really. So never stop being surprised with like and why do you want to run ground teas? Okay, so that's one example that was surprising to hear, but teeth. Yes, exactly. Ah, but of course, tears, saliva, urine, those are quite common CSF, of course, but then different types of biopsies also extremely important, of course. fine-needle biopsies, interstitial fluids, synovial fluids, blister fluids from ... burn victims. Wow. Interesting. Yeah, we have covered, I think, everything. Intestinal juice was interesting when we got there was some device that collected intestinal juice. So we ran it, and it worked. How interesting. So, I think a lot of these samples, right, where you don't even bother to quantitate how much protein is in the sample because you consume a lot of it. Right. And people don't know beforehand if it'll work. However, we have assurance that we use very small volumes. We were able to be very sensitive to pick up very low sort of amounts of protein available. Right? People just say, well, we don't know, therefore, we just need to go ahead and try it. And many times it works. Right. I mean, we have had applications where they said, we collected these very precious samples years ago, but we couldn't use it for anything. And now we have the opportunity and we could deliver extremely valuable data. So all of these fine needle biopsies or micro vesicles, tape strips, exosomes, cells. Yeah, exactly. So, huge impact. Yeah. These antibody hooks, right. They're hooking it out of this solution in such a low volume, it's, ah, pretty exciting. And then we haven't talked about the different species that we have done as well. That's the whole 'zoo' that we have done as well. So tell us. Interesting. Just to be clear, our protein targets are optimized or developed in R & D to, human with all but our mouse mouse panel. Right? We certainly have a mouse panel. And so when someone comes in and wants to understand what's going on with a cow, for example, what do you tell them and what are the most extreme examples that you've seen? Yeah, I mean, what we tell them, of course, exactly what you said, that we don't have any cow specific panels, but it's quite close homology for many of these species to humans, and they don't have any other better options, so we give them more data than they could get from anywhere else. So, of course, rodents, ... nonhuman primates, dogs, cows, fish, horse. Wow. So actually, they're able to measure proteins out of fish, even though we know that our antibodies are generated against antigens from humans, but still we're able to actually conclusively identify that the proteins measured. In a fish sample, I think the detectability in fish was low. So it's not anything we recommend normally. Yeah. With some underlying information that you can get from for specific proteins, you can get some interesting results out of it. It reminds me, again, bringing back into the genetics, is we worked on a whale project, and there are no SNP chips for whales. Right. So I think we use the same HapMap from Enroth et al. in 2014, to see how many SNPs we could find homology... across species. And it was actually pretty useful. So, yeah, interesting. It's coming back a little bit populational like the generation of big data. I know now that there are some projects running at Olink in regards of visualizing and integrating data with Olink Insight. Could you give us a little bit of feedback on that? Would you give us some comments on that just to get to know the more details? Do you refer to the big publication? Yes. Olink Insight is a very, very exciting new initiative that we have. So it's a digital knowledge platform for proteomics that we have built for our customers and community. And there is when looking at in the digital space, there's nothing of this kind on the market today. How we started that, we thought that since we see us as the leaders in proteomic assays, so we also want to be pioneers in the digital space and drive the development for more modern innovative tools to help. The proteome is very complex. The data analysis can be extremely challenging. If we can, with our insights and experience, try to support the community to faster come to conclusions and actionable results. By developing tools and connect different public databases and different annotation tools, we can help to support them throughout basically the journey. So I'm very, very excited about Olink Insight. So the difference we're going to have or we have different apps to support the analytics side as well as open data sets that you can use for validation or confirmation of a disease signature or compare with a healthy proteome, and also share data stories where it's like best practice analytics, ah, for different applications. So it's a fantastic platform. Yeah. One of the best features within that, that I've struggled with since I joined Olink is that conversion from gene name, where you have many different gene names for a single gene, converting that to the protein that is coded for by that gene. Right. Because in the genetics base, so many people work with genes, so there can be a dash in there or no dash in there, or there can be something that looks like a date. So you throw that into Excel and it's a real pain to look up DEC1. Right? But to be able to pull that out of Insight, it's such a simple thing, but it's got a nice functionality, that I think is just a microcosm of the bringing together of the genetics, and the proteomics. Just a nice example of how thought out it was in the needs. And for those interested in trying it out, it's free to use it's at insight.olink.com, One of the other interesting features that relates to the 1000 publications is the ability to search publications by Biomarker, is that correct Ida? Correct. So this is basically, why wouldn't I use PubMed versus this particular feature within Insight? No, exactly. And I think that's one of the features at Insight that you can go to PubMed, but of course, if you want to see the thousand publications in different categories, that's the place to go. But also in. general, it has very smart, smart search tools, but it's public information. But we have tried to make it in an even more user friendly interface, the same as with the Pathway Explorer that we call it, that is based on the amazing Reactome database. But it also has some additional layers to it where you can insert a list of your top markers and really see the underlying biological pathways and mechanisms. So it's a, fantastic tool to go there. You can download the images as well. Right. Once you got that publication set up. When I was playing with it, I was shocked when I clicked on a single node and the amount of information that I can find about that node in really well written prose with references and everything I wanted to know almost in like three or four paragraphs. It was remarkable work. A lot of work, obviously, has gone into it, and remarkable resource. Well, thank you, Ida, for joining us today. I really enjoyed this conversation. Are there any last words you like to share with our audience? No, I think this is just the beginning. I think still 1000 is an amazing milestone, but, I think already this year it's been I can be invited again when we reach be there you go. Absolutely. You are always welcome. Always. A big shout out to all of our both the early adopters that's been with us since the beginning and supported us. ... we wouldn't be anywhere without them. So those are the most important players here. Absolutely. For sure. All right, until next time. Thank you for joining us. Thank you. That's great. Bye. All right. Thank you for listening to the Proteomics in Proximity podcast brought to you by OLink Proteomics. To contact the host or for further information, simply email info@olink.com.