Chris Yip 0:01 Welcome to Tell Me More: Coffee with Chris Yip, the official podcast of the Faculty of Applied Science and Engineering at the University of Toronto. Each month, I sit down with someone from our vibrant global community to talk about what places them at the heart of designing bold solutions for a better world. You'll meet students, professors and alumni who are making a difference across a range of fields, including some where you may not expect to find them. My guest today is Nika Shakiba, who completed her PhD in our Institute of Biomedical Engineering in 2017. She's now an assistant professor in the School of Biomedical Engineering at the University of British Columbia, where her research focuses on stem cells. Using systems biology to understand how they work and synthetic biology to engineer new therapies and regenerative medicine. Nika, welcome to the podcast. Nika Shakiba 0:56 Thanks, Chris. Delighted to be here. Chris Yip 0:58 It's been a while. Nika Shakiba 0:59 I know it has been a while but I've been following you on Instagram and stuff so clearly, you've been having a lot of adventures, Chris Yip 1:07 A lot of adventures, a lot of fun, a lot of fun reconnecting with folks and I think back we just recorded a really nice one with Jenna. Also, UBC also an alum of IBME. Anyways, we kind of have to bring the audience up to speed on stuff. The usual question, tell us where you grew up and when that moment came when you realized engineering was where you wanted to be. Nika Shakiba 1:33 So I'll answer part one of that question first because it's actually an easy, it's a much easier answer. Chris Yip 1:38 Sure, sure. Nika Shakiba 1:38 Part two is more complicated. So yeah, I grew up in Toronto in the Greater Toronto Area. My parents were graduate students at University of Toronto, so they were living in student housing, and I was living there for a while and then, you know, they got jobs, and we moved out to Etobicoke and then Richmond Hill. So I always grew up in the Toronto area and so University of Toronto was a natural kind of place for me to consider engineering though, it was harder, harder sell for me. To be honest, I, I was very resistant to the idea of engineering, mostly because both of my parents are engineers, I come from a family of engineers (Chris: Uh-oh.) of various kinds, yeah, civil, electrical, we've got chemical, we've got all the engineers in my family mechanical. And I was like, you know what, I want to do something different. I'm gonna break this trend, I'm not doing engineering. And obviously, that didn't happen. So I got to grade 11, and 12, you know, when everyone was making decisions about their lives, and I just thought, I can't give up math, physics, I love it so much but I also love biology. So here's, here's what I'm gonna do, I'm going to intersect all of those things and I'm gonna go into a field of engineering that we don't yet have in our family, which is biomedical. So I'm breaking the mold, but I'm still an engineer. Chris Yip 1:39 Cool, the sort of work with the ultimate machine in a sense, right? The cell. Nika Shakiba 2:55 Exactly. You sort of say, hey, there is civil engineering going on in the cell. There's definitely chemical engineering going on in the cell, right? There's electrical, there's all the disciplines, they're just, you know, add a little bioengineering in there. Exactly! Got to push the boundaries of what engineering is so I felt excited to do that. Chris Yip 3:21 It really is. It's almost a natural intersection between biology and engineering and bring them together. Engineers love complex systems and I can't think of a more complex system than trying to understand how - we're going to talk about that in a sec - but how do cells work? What are they doing? How do they know what to do? Nika Shakiba 3:35 But you know, when I got into biomedical engineering, that was not my vision of the end game. Like I was not thinking about cells and engineering. I didn't even know that was a thing that biomedical engineers do so I was really flying blind and just following my gut. I was thinking about the more traditional biomedical engineering disciplines, you know, like, the more biomechanical prosthetics, the more bioelectrical devices and that sort of thing. So I came from that background, right, like, that's what my parents were, very traditional engineers and so this was all a new territory for me to explore but it was so exciting. Chris Yip 4:08 So you graduate your PhD in 2017 but you went all the way through Nika Shakiba 4:13 2006 was when I started in the engineering science program. Chris Yip 4:18 That, was that the year and we'll have to ask your supervisor at some point, your former supervisor, actually your current boss... Nika Shakiba 4:27 My forever boss. Chris Yip 4:28 Yeah, your forever boss Peter, we'll do a shout out to Peter Zandstra in the Zandstra Lab. Was, was 2006 the year? It might have been the year that we created the bioengineering minor. Nika Shakiba 4:39 It may have been. At the time it was the only option I had found, like engineering science, was the only option I had found for biomedical engineering, yeah. Chris Yip 4:48 Biomedical engineering was embedded in EngSci but I think also probably 2006, somewhere in that realm was when when we also realized that lots of our students were interested in bio plus engineering, and we launched the bioengineering minor for all programs. It was just sort of add to the engineering science angle of biomedical engineering. Nika Shakiba 5:07 Yeah, yeah, I do actually remember a peers who went into that minor so. Chris Yip 5:12 So you are the prodigal stem cell of biology and engineering for U of T. Nika Shakiba 5:18 Yeah, I am [laughs]. Totally U of T, through and through. Chris Yip 5:22 I use this analogy, I think I have used this in the past, that undergraduates are like stem cells coming in, because we perturb them a lot and we never know what they're going to pop out as. So we're gonna we're gonna keep that along. With that in mind, can you tell us a little bit about bioengineering and actually this idea of stem cells, because we've brought this into this context? Nika Shakiba 5:41 Sure. Yeah, stem cells are a super cool class of cells, they have two abilities that make them really special that other cells in your body don't have so one is that they're able to self renew, which means they can make copies of themselves theoretically endlessly. And the second one is that they're able to produce all the specialized cell types in our body. So they themselves are unspecialized, they don't have a specific function or ability, like heart cells that beat or skin cells that stretch out and cover our bodies, but they produce those specialized cell types that do all these functions. And so they are like the cell that rules them all, because they produce all the different cell types. Chris Yip 6:21 We'll just use that Lord of the Rings thing. Nika Shakiba 6:25 Yeah, they're powerful because imagine if you could engineer those properties, self renewal and differentiation to produce different cell types, you can control those, then you can really unlock the potential of a stem cell for therapeutic purposes. Chris Yip 6:39 Which is an incredible concept, right? And I think I mean, there's a long and storied Canadian history of this and I don't know if you want to tell or listen. Nika Shakiba 6:47 Yeah, proudly, because that's also from Toronto, it's a Toronto discovery. So 1961 was the first report ever in the world of a true stem cell. And that was the blood stem cells so the stem cell that lives in our bone marrow and give rise to all of our blood and that was made by two Canadian scientists, Drs. Till and McCulloch, and it was in Princess Margaret, so just across the street from all the engineering buildings. And it was so cool, because it was an example of what would happen when divergent areas intersect. So Dr. Till is a biophysicist and Dr. McCulloch was a hematologist. And so so cool, right? Those two fields that most people probably wouldn't think to intersect intersected and then out came this discovery of the first stem cell in Canada. And now we have a statue of the two of them. Maybe you've seen it? Yeah. Outside the MARS Center. Chris Yip 7:41 Yeah. And I think I mean, it's such an awesome story about sort of Canadian first and how it really launches a field and we've seen just an explosion, right? Of stem cell biology, stem cell biologists that the multigenerations of bio engineers have emerged out of this space. I mean, you could probably map a family tree of stem cell folks out of Toronto and where they've all gone, right? Nika Shakiba 8:08 Yep. A lot of researchers in the stem cell space, engineers and otherwise, are sitting on the shoulders of Till and McCulloch and that's my lineage, too. I didn't know that when I joined Peter's lab but you know, like Peter's PhD co-supervisor, Connie Eaves, had trained with Drs. Till and McCulloch. Chris Yip 8:26 You're now at UBC and I guess you've described your work as both forward and reverse engineering of stem cells and I mean, give us, our listeners a bit more of a view of what that looks like. Nika Shakiba 8:36 So I guess, as I was thinking about PhD and transitioning out from my undergrad, I did a lot of sort of core electrical engineering training in my biomedical systems major. So there was a bit of a paradigm shift that happened for me when I went into my PhD because I often thought about biomedical engineers as engineering things around biology, like, you know, devices, imaging modalities and then there was a paradigm shift when I realized engineers can engineer biology itself, like biology and engineering will substrate. And so the cell is like the center of all of that, it's a unit of life, it's a fundamental unit of life. But then I realized it's a fundamentally programmable unit of life and that kind of thought, that paradigm shift came with this 2006 discovery of reprogramming which Yamanaka and Takahashi were based out of Japan showed that you could take a skin cell or really any specialized cell that has a nucleus, that's all it needed, it needed to carry around DNA, and if it carried around DNA, you could change his identity. You could genetically engineer it so that it kind of forgets that it was a skin cell or a blood cell or whatever, and reverts it back into a stem cell state. And not just any stem cell but a pluripotent stem cell so the ultimate stem cell that can produce every single cell type in your body. And that can be done in a dish, right? Like we could just revert that skin cell back to a pluripotent stem cell. And it's such a relatively simple genetic manipulation that they did, this blew my mind and it actually blew the field's mind that they won the Nobel Prize in 2012, fastest turnaround time for a Nobel Prize, because they show that cells are so programmable and engineerable. So that's kind of what my lab is now built on, this idea that we can program functions and properties in cells. Chris Yip 10:31 In this area of forward and reverse engineering, give me some examples of where we can use this in practice. Nika Shakiba 10:38 The challenge with stem cells is learning how to control them, right? Being able to predictably and robustly control them, which is what we do with every other engineered system, like robots, computers, all those things are very predictably controlled but a cell is not something we've built and it's quite complicated, we don't fully understand it. So it's still a bit of a black box, exactly what's going on in the cell and how a cell decides to self renew or differentiate. And so that comes with the reverse engineering. So in my lab, part of what we're doing is we're trying to understand these rules that govern stem cells and what they decide to do. And particularly realizing that stem cells, at least human stem cells, and the cells that they compose, don't live alone, they live in multicellular societies so all of these interactions between our cells then have to be factored in to how they make decisions at an individual cell level and so we reverse engineer that. We use a lot of genetic engineering tools to be able to like tag individual cells, and then follow them around in these multicellular systems and then we build mathematical models to try to distill what's going on in those systems. And then forward engineering side, once you've kind of learned some of the rules that govern what stem cells can do, then we start to program those things, genetically programmed those things and thinking about DNA, like a programming code. And in terms of like, why, like, why would we want to do this, other than the fact that it's really cool to think of a cell as like a robotic type system, there's, there's really clear applications, and we're already seeing clinical trials that are involving stem cells. So one of our projects, for example, aims to create beta cells, which produce insulin so these are the cells that live in your pancreas and people who have type one diabetes, they're lacking their beta cells. So beta cells' job is to kind of sense when there's sugar in your blood, and then to release insulin in response to that sugar and that helps regulate the levels of sugar in your blood, which is really critically important for your body's homeostasis. And so you can actually create beta cells from pluripotent stem cells, you can coax them to differentiate along the trajectory of becoming a beta cell. And if you can produce these beta cells on demand in manufacturing pipelines, then you can transplant those beta cells into patients with diabetes, and theoretically cure their diabetes, because you're giving them the cells that they're missing. And so just being able to do that differentiation process, robustly, predictably, with high efficiency, high yields, so that everyone can benefit and it becomes cost effective as a treatment, that's a huge engineering challenge. Chris Yip 13:18 The idea of control, right? The ability to sort of either turn it off, or turn it on and cycle things around is something that engineers are used to dealing with kind of the normal context of that, like, we want to control how the train works, or how the plane flies, and we want to have robust controls around it. And then you've got a living system, which is kind of at some level trying to not be controlled by you, but being controlled by its surrounding environment, right? Nika Shakiba 13:45 Yeah, it's super complex, we don't know all the rules and here we are just kind of picking at particular nodes and perturbing, as you said, and seeing what happens. So that's part of the reverse engineering, it's like, let's just poke around in the cell, and see what each of these genes do, right? Or each of these signals do. And then once we've gotten a hang of what a few of them do, we can start messing with them in a more engineered way less tinkering, or engineering, and try to get predictable outcomes. Like really, we can turn those cells into beta cells. It's remarkable that we could do that in a dish, right? We're basically mimicking our embryonic development process in a dish, Chris Yip 14:19 This sort of idea of sort of linking sort of complex subjects, like a cell, which seems simple, but actually isn't and being able to make it accessible to the public, right? And to all ages is something which is I know is super important to you. Can you tell us more about what you what you've done both as a grad student and now as this new thing that you've gotten, and I'm gonna let you tell our audience what that is? Nika Shakiba 14:43 Sure. Yeah, so as a grad student, I did a lot of stuff with the Engineering Outreach Office. I was a DEEP instructor for like, seven years in a row, something crazy like that. So I was in the, you know, teaching and the DEEP program with high school students. Chris Yip 14:57 We should let people know what DEEP stands for though. Nika Shakiba 14:59 DaVinci Engineering Enrichment Program. Chris Yip 15:02 Right. Nika Shakiba 15:03 It's wonderful. It's a high school science summer camp type outreach program and it's very immersive, hands-on, you spend like a full week exploring a field or a topic of your choosing and there's so many different courses to choose from. So I had one in the biomedical stream, shocker, all about regenerative medicine so it was really it was really fun to see, high school faces light up when they realize like, oh, yeah, engineers, like, we, we mess around with biology too, right? That's like, that's a sandbox that you could play and do. So, so I did that, I did Let's Talk Science. I used to help run the chapter at the University of Toronto, St. George Campus. And then I did a lot with Stem Cell Talks. That was one of my passion projects. So Stem Cell Talks was a symposium that we ran every year for high school students and it kind of brought science and ethics of stem cells to them, but in an interactive way, like we would bring researchers up to the stage, and they would debate each other on hot topics in the field and we'd bring ethicists in and do cool panels around the ethics of stem cells. And then we got to expand that so I took that over from three graduate students at U of T and one of them was who was in IBME who had started that initiative and I took it over and we helped expand it to nine cities across Canada. And it still exists, it's really fun to see that. And now I'm actually speaking at Stem Cell Talks Vancouver in a few weeks. Chris Yip 16:24 Cool, cool. Nika Shakiba 16:25 It's super fun. So yeah, I had I had a lot of involvement with outreach. It was a really nice outlet to remind me why I'm doing what I'm doing because so many days in the lab where they ended in failure, all the experiments on the cells got contaminated and they died but doing outreach, you had to distill the essence of why you were doing the science and the engineering that you're doing and so it renewed my, my passion for it was great. And then when I went off to my postdoc, I co-founded this new proud passion project of mine called advice to a scientist and the idea was to try to take some of the luck and chance elements out of finding mentors, strong mentors, who prop you up and empower you throughout your training pipeline, you know, throughout academia, for all areas of STEM, science, technology, engineering, math, and medicine. And so we created this online hub, which you can visit, advicetoascientist.com. And we started to rally members of our community to write these scientific-articles-style review papers, where they would like distill evidence from different sources on different topics. So whether it was like academic interview, getting ready to interview for academic jobs, or like how to make a poster, basic stuff, right? And we got them to kind of write review articles and now we're building that out so we're building Advice for Scientists out and it's largely run by graduate students so our team is largely graduate students who, who just want to build out skills, who want to get involved in the community and yeah, it's an ever evolving project. Chris Yip 18:06 Hey, let's cycle a little bit back, like you've gone through this whole system, you, you're now at UBC. What was it like to transition to being a prof, to being on the I called the other side of, the other side of the lecture theatre? Nika Shakiba 18:20 Yeah, it's, it's an interesting transition. Every day is an adventure every day is different, in the sense that, you know, like, I now wear way more hats than I was wearing before. I'm teaching but then I have like, run this research lab, I got to hire for the lab, you know, like all the students, keep them going in their projects, and mentor them in their journeys, and then also keep grants rolling in to keep the funding going. It's just like, all these different hats and it makes it really fun because no, two days are the same but it's also quite challenging, because I don't think my training really trained me to be a manager, and you know, all these different hats, you can't possibly, financial management, like, you know, I'm learning as I go. So I think lifelong learning, serving me well, probably. Chris Yip 19:10 You needed someone to start Advice to a Scientist [Advice for Scientists] before you started it, eh? Nika Shakiba 19:16 Yeah, but you know, what's funny? Part of what led to Advice for Scientists was the realization that like, I'm getting advice, like, I have all of these very active mentors who like want to tell me what to do and what to expect, including yourself, who had given me a lot of advice too. And so this, but it was so like luck dependent. It was just like being in the right place at the right time interacting with the right person and can we take some of that away like and make it more accessible, like open access advice sharing. So that was the whole kernel. Chris Yip 19:47 It's honestly amazing to see, like, where you've gone and how you've succeeded in your career, and it's a blessing actually to see, right? To watch (Nika: Thanks.) students kind of come through this system and realize, you know, I was gonna say where the perturbation was like, I don't want to take that, take credit for it because you did it all on your own (Nika: No.) but it's sort of like the role that, that the school and the university and everybody's played in, in helping people forward, right? It's cool. Nika Shakiba 20:13 It was the perturbation, it was absolutely the perturbation that I needed to differentiate so... Chris Yip 20:18 There you go. With that in mind, right? And actually, you have, you are actively giving advice, but what would you say to the, I don't know, the EngSci applicant that's coming in for this coming September, let's just say engineering, it's all engineering. Nika Shakiba 20:34 I would say, for me, the key was always following my gut. Like, as you saw, I didn't have some grand plan. I didn't even know what biomedical engineering really was until I immersed myself so I think like, having the ability to self reflect and identify the things that make you really excited, right? What makes you really passionate, and to use the engineering arena to explore that, because engineering touches everything, like engineering is part of every aspect of the world. So find the aspect that you resonate with most and then, you know, develop your core skills in that area and apply yourself and the sky's the limit. Like I've seen people use their engineering degrees to do things that I never imagined an engineer can do, right? Similar story for me but I guess I was not as creative as some of the other people realize, you know, you can use engineer for literally anything you want to do. So really utilize the experience, it provides a really nice playing ground to develop as a multi dimensional person, not just in the technical skills, but also in the soft skills, the ability to distill, you know, key principles from complex systems that can be applied everywhere. And then in the very transferable lifelong learning skills, engineering really equipped that me I think. Chris Yip 21:54 Yeah, it's about, it like, as you sort of said, it's about building the foundation, but also letting this give people the space to explore the ability to take that and say, you know, I want, I'm interested in this sector, and I'm going to apply these skills here and to work at those disciplinary boundaries to break down the like, the classic sort of silos, right? Nika Shakiba 22:13 Yeah, that's what I love. Yeah. And I think that is ultimately what an engineer does really well, especially a biomedical engineer. We're kind of poised to be this node, where different spokes kind of connect, and we can speak the language of all these different people, the biologists, the more technical computational people, right? The quantitative side, the soft skills, like if you can collect all of those skills, then you can serve as these nodes for really interested, interesting, interdisciplinary collaboration. And that's ultimately how innovation happens. Chris Yip 22:43 So here, here's a question for you. Since, since you arrived at UBC, which also happened during the pandemic, what was the most unexpected conversation that you've had? Nika Shakiba 22:56 So this one has roots in Toronto, so I don't know if it still counts, but it actually came to fruition at UBC. Chris Yip 23:02 Perfect. Nika Shakiba 23:02 So I now have a collaborator who is a game theorist and I met her talking to her on a subway platform in Toronto coming out of a symposium that was being held at University of Toronto, by Medicine by Design. And she just kind of looked at me and said, "Hey, you came from the symposium like, what do you do?" And I told her, "I'm a stem cell researcher, stem cell engineer." And she said, "Oh, cool. I'm a game theorist." And I was like, "Game theory. That's so cool. What are you doing here?" And so we've stayed in touch and we now have a grant together with her. She's based out of Gary Bader's lab at the University of Toronto and together, we're using game theory, and we're using other fun computational models to capture cell to cell games. Chris Yip 23:45 Okay. Nika Shakiba 23:45 So I'm learning game theory. It's really fun. Like, I never thought I would do this, right? Chris Yip 23:51 That's exactly it, right? It's about that curiosity, right? Looking over and something that sparks, this is an interesting question. It can lead you down, like you said, some really interesting and ultimately productive paths. This has been an awesome conversation, Nika. And it's just been so great to catch up and hear I mean, both hear about how you got to where you are, I mean, I knew a lot of the story, but I think I had to kind of, you know, let our listeners in on the secret of your success as it were and how you got to where you are, and it's been an absolute pleasure to follow your career, continue to follow your career. Nika Shakiba 24:27 Thanks. I really appreciate all of the the mentorship and the advice sharing and it really has a, an impact. It perturbed me correctly. Chris Yip 24:35 Again, thank you so much for being here as being part of the podcast today. Nika Shakiba 24:38 Thanks for inviting me. This has been fun. Chris Yip 24:41 Thanks again for listening to Coffee with Chris Yip. If you want to catch up on past episodes, or make sure that you don't miss the next one, please subscribe. We're on Apple Podcasts, Spotify, and more. Just look for Coffee with Chris Yip. You can also check out @UofTengineering on Twitter, Facebook, Instagram and LinkedIn for more stories about how our community is building a better world. And finally, if you'd be inspired to join us, we'd love to welcome you. Whether you're thinking of taking a degree or working with us on a research project, you can find us online at engineering.utoronto.ca or you can visit our beautiful campus in Toronto, Ontario, Canada. I hope I can join you for coffee soon. Transcribed by https://otter.ai