Hannah Rosen: Hello everyone and welcome to New Matter, the SLAS podcast where we interview life science luminaries. I'm your host, Hannah Rosen. Joining me today is Sam Berryman, winner of the 2023 SLAS Graduate Education Fellowship Grant, and he's here to tell me all about his exciting research. Welcome to the podcast, Sam!
Samuel Berryman: Thanks for having me, and I'm really excited to be on here.
Hannah Rosen: Yeah, it's our pleasure. So, to start us off, can you just kind of briefly summarize your proposed research for the SLAS Graduate Education Fellowship Grant?
Samuel Berryman: Yeah. CAR-T cell therapy is a new form of cancer therapy that modifies the patient's own immune cells in order to give them the ability to target and kill cancer cells. So, these therapies have been shown to be highly effective against certain cancers like B cell lymphoma. However, a major challenge in the application of these therapies is that many of the modified immune cells don't actually participate in the killing of the tumor cells as intended. At least that's the way we see it, and this variability increases the potential for side effects, as well as gives rise to higher dosage requirements that results in greater cost and reduced accessibility for patients. So, in order to determine why only a small subset of those CAR-T cells are functional, I'm working on developing technologies to study these cells at the single cell level, and we're sort of developing this new platform for investigating this based around our nano well devices.
Hannah Rosen: Wow, that's really cool. So, you said that only a small subset of these CAR-T cells are actually targeting the cancer cells as they're supposed to. What are the rest of them doing?
Samuel Berryman: Yeah, that's a great question. So, they're still secreting cytokines and behaving how they normally would because they are a T cell. And that's kind of the problem here is that we're putting them into the patient and they're not behaving as expected, but they're still contributing to some of these side effects, and it's a large number of them too. We've had some of our experimental studies where we start looking at, you know, like 50% having sort of a low behavior and even 25 to 30 literally doing nothing when they interact with cancer cells.
Hannah Rosen: So, if they’re still, you know, releasing cytokines are they, then, you know, killing healthy cells in the human body?
Samuel Berryman: Yeah, they're at almost killing the person, to be honest. So, one of the big risks with this treatment is this thing known as cytokine release syndrome. That is caused by all of these extra cytokines being released at super high level and it can cause issues ranging from like, a small fever in the patient all the way up to organ failure and neurotoxicity. So, there's major complications that are associated with this therapy that we wanna try to mitigate.
Hannah Rosen: Oh, yeah, absolutely. I mean, those sound like some pretty major complications. So how often are you able to use, or I shouldn't say you, presumably you're not doing this with the patients, but how often are doctors able nowadays... is this something that we're actually able to use in a clinical setting where patients are receiving CAR-T treatments, or is this something that's still in the theoretical stage?
Samuel Berryman: This is absolutely in the clinic. It's being used, although right now it is quite expensive depending on where you're getting it. I believe there is just a massive number of clinical trials for other cancer targets. Like I said, it really started with B cell lymphoma, which is kind of interesting because B cell lymphoma, right, is B cells. And it turns out if you just kill all of the B cells, you eliminate the cancer. And the B cells will come back later, right, will regenerate. That was the proof of concept with CAR-T cells where they said we can target B cells, cure cancer in these patients, and it has been quite successful.
Hannah Rosen: Well, that's amazing. So, it's not so much that the... the CAR-T cells are seeking out cancerous cells, they're just eliminating an entire type of cell.
Samuel Berryman: However, like, you know, I don't wanna just say that's what they're doing because there's so much research right now on trying to identify cancer markers on cells and then tuning the CAR itself to be able to recognize those cancer markers, and that almost gets to the point where it's patient specific.
Hannah Rosen: Can you tell us, you know, I... I feel like we always see CAR-T written down, can you... what... what does the CAR stand for in CAR-T cell therapy?
Samuel Berryman: Yeah, exactly. So, the CAR stands for chimeric antigen receptor, and the T of course for T cell. So, we take a patient’s T cells, and then it's modified using a lentil viral carrier. So, this... the genetic material is inserted into the genome so that it will sort of create this receptor, which is then presented on the surface of the cell.
Hannah Rosen: So, does the success of this treatment, because you said that we're taking the patient’s own cells, their own T cells, and genetically engineering them, so does some of the success or failure for these treatments depend largely on the patient themself, or is it more of how we're modifying the T cells?
Samuel Berryman: Yeah, and that is a great question. That is really an aspect of our research where we're trying to say that, you know, there is this heterogeneous population of T cells, not just on the specific subsets of T cells that we know, but even among those subsets. And that behavior is going to be different patient to patient. And we need to start understanding why, and what's causing those effects? Because if that's our starting manufacturing material, we need to characterize it a little bit better.
Hannah Rosen: So, how is your research going to go about solving this problem?
Samuel Berryman: We really want to start looking at the single cell level to try to identify the subsets of cells that are better at killing the cells, and we don't want to stop there. We don't just want to run this experiment where we say, hey, this cell is really good at killing cancer. Afterwards, we want to retrieve those cells and we want to investigate different internal regulatory sort of stuff that's going on as well as any surface markers or anything else that we might correlate with the behavior so that we can modify the manufacturing process.
Hannah Rosen: So, can you discuss a little bit what the role that is... that machine learning is going to play into your research?
Samuel Berryman: I love that question because, you know, there's so many sort of new pitches or products that come along and people try to, you know, kind of throw machine learning in because it's a great way of getting in the door in some places. So, my background, I focused extensively on computer vision. I think that's a really important building block for going into this space. So, if we use classical segmentation approaches because we are doing microscopy imaging, you can expect a sort of a cell segmentation error ranging around 10 to 15%, and that's just among rounded easy to segment cells. So, in our case, we're working with T cells which go from compressed to an elongated state, which makes that even more difficult. So, we use machine learning models to do sort of semantic segmentation of cells... our nano wells, and even to the extent of making sort of outcome classifications or regression predictions of our nano experiments, and we really, really need to do that, I should say it's... it's about overcoming that error. So, since we're looking for a rare cell population, if we have a 15% error just in what we're observing, that's going to be a huge problem. Because we're already talking about running these experiments on the scale of about 500,000 at a time, and that 15% could be critical.
Hannah Rosen: Yeah, yeah, that's a lot when you look... get... get to those numbers, yeah, 15%, that's gonna be a very high number there. So, what made you interested in this topic in the first place?
Samuel Berryman: I find single cell research to be an extremely interesting and rewarding field because it unmasks many of the assumptions that we make about the discrete cellular phenotypes and cell types that we know. So, there are subpopulation variations that we really don't quite understand yet. We just chop it up and say the cell type mostly behaves one way or another, but with new advancements in the biotech space, studying these single cells is becoming, you know, not only an option, but a huge opportunity for innovation.
Hannah Rosen: Is that one of the reasons you maybe got interested in T cells specifically, is because you said there's so much variation in the different types of T cells that we’re kind of only really starting to scratch the surface of it seems?
Samuel Berryman: Yeah, they're... they're super complicated. And I gotta say it... like, they're difficult to work with and there are days where you're frustrated and you're like, did I make the right decision? I... I... I think I did. It can be frustrating, and that might also just be why we don't know that much about them, at least from my point of view.
Hannah Rosen: Well, I mean, it sounds like that's a great justification perhaps for your research is that we need better ways of studying these really difficult cell types especially.
Samuel Berryman: Yeah, if you can come out of it and just say hey, this is how you use these and study these, that's an important finding.
Hannah Rosen: Yeah, absolutely. Well, that's really exciting. I mean, it sounds like really important work and I definitely can relate to the desire to want to do the research on something that no one else is doing, and then you get started doing the research and you're like oh, this is why no one else is doing it. It's because it's really, really hard. But perhaps it's where the best... the best innovation comes is when you, uh, you gotta solve that problem. Someone's got to anyway.
Samuel Berryman: Yeah, if you tackle an easy problem, it's, you know, a lot of other people are gonna be working on it as well.
Hannah Rosen: And where's the fun? Where's the fun in tackling the easy problem that's already been solved?
Samuel Berryman: Yeah, you definitely learn a lot more from doing something difficult, absolutely.
Hannah Rosen: So, can you tell us a little bit of, you know, how will this SLAS Graduate Education Fellowship Grant help you with fulfilling all of these research goals?
Samuel Berryman: So, I believe the SLAS Fellowship offers me an excellent opportunity to establish connections with peers in the community. And, you know, I'm not just saying that to sound nice, I've already started forming these new connections. So just last month I attended the SLAS Conference in San Diego where I was giving a talk, and that conference was a huge help in facilitating contact with current and new suppliers, but also initiating conversations with new partners and collaborators. And I can't stress enough how helpful that was for my research that actually resulted in changes to my experimental methods. Just three days after the conference I was back in Vancouver and I had a rep from the conference in our lab talking to me about solving some of our problems, and quite literally today I have two new products arriving to our lab from suppliers that we're testing out, or another one that we're forming a new collaboration on a study with. And those are both people that we met at SLAS, you know that's just today. So, I really do see the fellowship as being an opportunity to enter this great community that's just filled with brilliant organizations and opportunities.
Hannah Rosen: Well, I love to hear that. It's so great to know that it's not just about, you know, the money. It's also, you know, building those connections and fulfilling that conversation and really helping to... to expand the idea of the research itself. That's really exciting for us, you know, so thank you.
Samuel Berryman: Yeah, I am really, really excited about the professional sort of opportunity here and a nice way of entering into the biotech sector of which SLAS is involved.
Hannah Rosen: That's great. So, can you tell us a little bit about, you know, your education? Where are you in completing your PhD? Whose lab are you working in? You know, tell us a little bit about your educational journey thus far.
Samuel Berryman: So, I come from a little bit of a different area. I have an engineering background. I actually did my undergrad in mechatronics, so more of the robotic side of things. And then in my graduate studies, I focused much, much heavier, very heavy on the biomedical aspect of things. So, I'm sort of in the final phases of my PhD where I've developed this technology, right? A lot of the software that goes into it and the experimental methodology, and right now the stars are just kind of starting to align where you... you know, you do all of the upfront work and then at the end it's like, OK, gather data, data, data, data, analyze and let's go. So, I'm really, really excited about where we're at right now and the potential for the data we're going to generate.
Hannah Rosen: That's great. Where are you doing all of this research?
Samuel Berryman: So, I am at the University of British Columbia. We are a member of the Center for Blood Research in the Life Science Institute.
Hannah Rosen: That's great. So what are your, then, your long term career goals? You know, you're nearing the end of the PhD it sounds like. What do you plan on doing afterwards?
Samuel Berryman: So, I think that what comes next for me is going to be entering the biotech sector. As I said, we are actually looking at potentially commercializing some of the research that I developed. So, we've sort of made this small device and we're trying to follow up on that. But I really think that I'm going to... I would like to end up in this area, single cell research, and trying to delve deeper into it in more of the private sector sense.
Hannah Rosen: That's fantastic. Well, you know, once you do get your start up, up and running, we have a great opportunity at the SLAS conference in Innovation Ave. So, you'll definitely have to come back when you've got a big fancy biotech startup to... to exhibit!
Samuel Berryman: I mean, if things work out, it could be a really good opportunity going through this fellowship.
Hannah Rosen: So, do you have any advice for some young PhD students out there who are trying to obtain funding for their research? You know, what advice would you give them?
Samuel Berryman: The advice I give them is, you know, don't stop, don't give up when you get a rejection, because you're going to get a lot more rejections before you get accepted. But also, make sure that you have a, sort of a really close communication with your professor and senior members of your lab, cause anything you write or develop or send, you need to get other eyes on it. You need to have them reviewing it. It doesn't have to be you alone trying to develop that writing material. But other advice that I might give, and this is just something that I found really successful, say, at my talk at SLAS for my research, I actually created a brochure. So, when you go to give a talk, sometimes it can be a little bit upsetting that you go and give a talk and there's not many people in the room, right? And that can get a little bit frustrating for you and you don't feel like you've reached the size of audience that you wanted. So, I made this brochure and, you know, three days before my talk, every day I was going out and I was trying to find the people that I wanted in my talk, and so I also, I spent three days recruiting people just to come listen to me, and that was actually very successful because in my talk, you know, I had a a rather full room and that is going to lead to more opportunities to talk to people and make these connections.
Hannah Rosen: Well, that is a fantastic idea. That's not something I've ever heard of anyone doing before, and now that you say it I'm like, why aren't people doing that, that's such a good idea! Especially if there are specific people that you really want to attend your talk, go seek them out, especially if you're later on in the conference. That's a... that's a brilliant idea.
Samuel Berryman: Yeah, I'm like, maybe I shouldn't have said anything, I should have kept it to myself.
Hannah Rosen: No a year from now, that's gonna be the trend, everyone's gonna be doing it. They're gonna be handing out brochures, passing out cards. You're gonna start a new wave of how people approach conferences. Well, Sam, thank you so much for taking the time to sit down and talk to me today. It's been really fun to get to know a little bit more about your research and we really look forward to seeing you at more SLAS events in the future and kind of following where your research goes.
Samuel Berryman: Also thank you so much for having me, this has been awesome.
