People of Science with Jon Choy

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Synopsis: In this episode, we speak with Sarah Cai who is a 5^th year biomedical engineering PhD student at Columbia university. With her graduation around the corner, Sarah reflects on her research and living experiences thus far while providing some valuable lessons along the way. Tune in as she speaks about the fruits of New York, how she drew inspiration from covid vaccines to complete her research thesis, and the unconventional career path that’s in store for her post-graduation.

A life outside of science: Sarah underscores how research can easily narrow our periphery, indirectly/directly breeding an identity solely based off our successes and failures. This one-dimensional identity is dangerous as one’s mental health will be in jeopardy, and is the reason why sowing other parts of ourselves is required for ensuring sustainable high-quality work—Sarah has made efforts to do so, including having joined the Cecilia Chorus of New York, regularly attending concerts (Kpop, R&B, indie), and practicing pottery. Importantly, these creative and artistic outlets have facilitated a healthy balance between her professional and personal life that allows her to work at a high level while minimizing burn out.

Concrete jungle: Sarah did not apply to any schools in New York for undergraduate partly due to the overstimulating urban environment at these universities, and her preference for a stronger campus feel. For graduate school, though, Sarah believes that New York is an amazing place to be during one’s early-mid twenties—well suited for the inevitable changes and growing that occurs during this life stage. She appreciates the cultural diversity in New York and how there is always something to do (food, activities, music etc.)  

Pre-med turned pre-sci: Sarah’s earliest memories were of her and her brother playing doctor, and recalls a natural desire to fix things. This contributed to her early aspirations to become a medical doctor, so she pursued bioengineering on the premed track during at Upenn during her undergrad. After a tough first year, however, Sarah began exploring her interests in research—engaging in a dermatology immunology internship at Johns Hopkins and an internship in drug delivery lab at Upenn. This ultimately led her to pursue PhD programs in bioengineering with a specific interest in the delivery of therapeutics.

BBB? No problem: Sarah’s thesis focuses on non-viral gene delivery to the brain. . umm what does that mean and why does this matter?? Many neurodegenerative diseases (Alzheimer’s/Parkinson’s) have some genetic link, so therapies that can effectively deliver genetic material to affected cells to either compensate for a loss or edit their genome is of great interest for therapeutics. Two major obstacles in delivering genetic material to cells (neurons) in the brain is (1) passing the blood brain barrier (2) doing so in a safe and effective manner. The blood brain barrier (BBB) is highly selective to things that can pass—Sarah takes advantage of a novel technique, developed by a neighboring biomedical engineering (BME) lab at Columbia, called focused ultrasound which can cause microbubbles (previously administered to patient) to expand and expand the BBB to allow the genetic material to pass into the brain and into neurons.. . this genetic material is not just free floating though. Typically, there are viral and non-viral ways to deliver gene/genetic material to cells. Sarah initially tried using polymeric systems to deliver genetic material, and while it was effective it was extremely toxic. After some intense brainstorm, Sarah took inspiration from the covid vaccines. These vaccines utilized lipid nanoparticles, non-viral vectors for deliver genetic material to cells. Fortunately, implementing lipid nanoparticles in the context of gene delivery to neurons brain worked effectively AND safely. Yay! 

Teamwork makes the dreamwork: Sarah reinforces how no one succeeds alone, acknowledging how if not for the efforts and support from her mentors, colleagues and collaborators she would not have been able to complete her research thesis project. Ultimately, having people that show you the ropes and people to brainstorm ideas with are key pieces to a successful research outcome. She is particularly thankful for Dr. Sima Lau, a postdoc in her lab, who taught her everything about gene editing; graduate students in Konafagou’s lab who taught her everything about focused ultrasound; Cody slater, a MD-PhD student in Wang’s lab who taught her intracranial surgery; and also her mentees how helped with her project.

Cohesively disparate: Sarah works is a graduate student in lab located on the Columbia’s medical which is separated by the main campus by nearly 50 blocks. This arrangement has made her feel, in some sense, slightly removed from the main campus sphere. Despite this, Sarah recognizes the strong research collaboration between the two campuses and the events held on each campus which help facilitate a more cohesive campus feel. Also, Sarah notes that she lives closer to the main campus than to the medical campus, allowing her to more easily catch up with her friends and be involved there.

All these difference career paths?? Unlike other doctorate degrees, PhD graduate have a wide range of post graduate paths they can pursue. While the conventional path for PhDs is academia, there are many options within industry including finance and consulting. Interestingly there are two branches of consulting: management and life sciences. Sarah details how the former is involved with more larger scale problems with broader implications, while the latter is more focused on helping a company prioritize different aspects of their pipeline. Sarah also touches on equity research and healthcare investment banking as other potential career paths for PhD graduates.

Marriage of biz and sci: Sarah’s past experiences have steered her towards career aspirations outside the conventional path of academia, and instead a more unconventional path like consulting. Past formative experiences have promoted an interest in the marriage between business and science: her minor in engineering entrepreneurship at Upenn, internship at a medical device startup company, and internship at a consulting company in life sciences. Reflecting on these experiences, she believes that her PhD has equipped her with problem solving and team management skills necessary to succeed in careers that implements aspects of business and science. In one year she hopes to be settling in at a position, gaining more business experience; in five years she hopes to be more comfortable with the business side of things; and in 10 years…. who knows!

Pivot, set, seize: Perhaps Sarah’s most important lesson during her PhD is to not be afraid of trying new things and being open to pivot towards new directions. I like the catch phrase she uses to highlight this message, that “you can’t always predict the future, but you can create it”. Sarah is alluding to the unexpected reality of life, which can easily derail us from a goal we initially set out for ourselves—however being open to pursue new and different directions can empower and help us achieve our goals in unexpected ways. Sarah could not have successfully developed a technique to safely and effectively deliver genetic material to the brain had she not been open to trying out new methods (lipid nanoparticles), when polymeric systems yielded toxic results in vivo. Additionally, it is crucial to set smaller stones to make overcoming challenges less overwhelming and manageable. She also suggests listeners to seize good opportunities when they come, as they can make the world of a difference in your profession and academic career. And finally, for those who are interested in applying PhD programs . . make sure that it will be the right fit (e.g. location, program, etc.) I like how she points out that the interview process is also a time for you, the applicant, to assess whether the school will be a good fit.

Transcript

[00:00:01] Jon: Hi, everyone. Thank you for joining me for another episode of the People of Science podcast. I’m your host, Jon Choy, and my goal is to highlight the experiences of people in science because I believe that the experiences of other people can inspire deep reflection and be a powerful tool for clarifying our own convictions and aspirations.

Whether you are considering if a PhD is right for you or currently a graduate student, I hope that these conversations can be a helpful resource for you.

 In this episode, we speak with Sarah Tsai, who is a fifth year biomedical engineering PhD student at Columbia University. With her graduation right around the corner, Sarah reflects on her research and living experiences thus far, while providing some valuable lessons along the way. Tune in as she speaks about the fruits of New York, how she drew inspiration from COVID vaccines to complete her research thesis, and the unconventional career path that’s in store for her post graduation.

so I’m really excited today to talk to you. I guess we should start with sort of maybe something more lighthearted, which is just I think a common thread for a lot of people and something that’s really important, I think, is to have hobbies and to sort of kind of have this work life balance.

So maybe you can talk us through some of your hobbies.

[00:01:23] Sarah: Yeah, definitely. That’s a great topic to start with. I, first of all, I love music. So I’ve been pretty actively involved in a chorus called the Cecilia Chorus of New York. It’s a community choir. One of my friends actually told me about it when she moved to New York. Her sister was in it and so she joined.

Really loved it. I went to one of her concerts. We perform at Carnegie hall, which is super cool. And so I went to one of her concerts and I was like, Oh my gosh, they’re amazing. So audition and joined, and it’s been such a wonderful community because there’s people of all ages. I think our oldest member is 92 and our youngest is probably like fresh out of college.

So yeah, it’s a really, really fun, really cool community and we do really great music. So that’s kind of one aspect is a nice, like artistic outlet. And then I also started doing pottery a like last summer. So just a couple of weeks of that, but that was really fun. And I felt like that was a nice way to kind of physically get stress on my body.

And yeah, there’s a lot of, you know, museums and like art and music and concerts and things like that. So I like to participate in all of those aspects. And I think being in New York is such a blessing because there’s always like, you know, classical concerts, but then there’s also like K pop concerts.

I got really into K pop over COVID. So I attended a bunch of those like R& B, indie, all of that. It’s such a lovely music scene. So that’s been a huge, like booster to my, to my mental health too.

[00:02:56] Jon: Yeah, I love that sort of the music and also the art. So I love that you’re in a choir. That sounds super fun. And then, yeah, the music and concerts, that sounds also super fun being in, in, being in New York. How do you think these hobbies have sort of allowed you to if at all be, be more productive at, at, at your job, which is doing research as a graduate student?

[00:03:20] Sarah: Yeah, so well, so I listened to your last podcast actually with Lucas and I loved the perspective that he had on it that he was saying, you know, you really need these outlets and also other passions outside of your maybe main passion so that you don’t get this dangerous type of tunnel vision where it’s like all consuming that you’re all of your successes and failures.

So your like highs and lows are dependent on research. This one thing, which tends to have a lot of failures along the way. So I think it’s been a nice way to kind of like get back in touch with reality. I mentioned, you know, the choir is such a lovely community. I think being able to hear about all of their stories and learn about everyone in the choir.

And also I love cooking and I, I find that a lot of chemists are good at cooking because it’s a very precise process. So that’s something I really enjoy. And I feel like it’s a, a way to like have this outlet to kind of balance your one like professional passion with all of your the other parts of your identity and other parts of your interests.

[00:04:23] Jon: Amazing. Yeah, hobbies are really important to sort of have the sustainability in, in your, in your vocation. And that is actually what I also want to get into, which is you are a graduate student, and Doing research is a large part of your daily life. Maybe before we get into your actual work and the amazing things that you’re doing do you think you could walk us through how you got to where you are today?

[00:04:48] Sarah: Definitely. So I’m currently doing my PhD. I’m a fifth year PhD candidate at Columbia University in New York. And I study specifically biomedical engineering and the title of my thesis work is non viral gene delivery of nucleic acids to the liver and the brain. And so to kind of like break that down how I got to where I am today, I think I’ve always grown up really curious about the natural world and I also like when I was young, like to play doctor with my brother.

So just go around pretending to get hurt and then try to fix each other. But I always knew that I wanted to help people and I was really invested in medicine. And I thought, okay, maybe I’ll just be a doctor when I grow up. And so I went into college. I went to the University of Pennsylvania and studied also bioengineering, which I think there’s these two terms, bioengineering and biomedical engineering that are used pretty interchangeably. So yeah, bioengineering also with geared towards medicine. And at first I was on the pre med track and actually I think my first year of college was like such a shock to me.

Cause this is not at all to say like high school was easy, but I definitely kind of coasted through most of high school, to be honest with you. And so like my first year of college taking all these really advanced courses, I was like, Oh my gosh, this is like so much and so hard. And so I didn’t end up doing super well my first year.

And I was like, okay, I’m never going to recover this hit to my GPA. So then I decided I was going to give up on pre med. But that, you know, not to discourage people who want to do pre med, I don’t think that’s like the right attitude to have, but that’s what I thought my first year. So I decided, okay, I wasn’t going to do medicine anymore, but I still was interested in it and still wanted, and I loved like the coursework I was taking.

So biomaterials, you know, how to use materials to design things to heal the body and deliver things to the body and therapeutics and things like that. So I think all of the coursework was still super interesting to me. And I was like, okay, I still know I’m interested in research. I’m interested in building things.

And so I ended up interning at a dermatology immunology lab the summer after my freshman year. And that was at Johns Hopkins. And that lab was such a wonderful environment. I think that was when I first fell in love with research because all of the people I worked with were so incredible. I had such amazing mentors and Also just like had really stimulating conversation with all of the people in the lab about, you know, how do we attack atopic dermatitis? How do we understand the different inflammatory pathways in the body? And so that was something that really stimulated my young mind.

And I was like, okay, I like research. I want to continue doing it. So I sought out more opportunities at Penn to do that. So I did several semesters of independent study, they call it, but it’s just like full time research in a lab. Or I should say part time research in the lab. And that was in drug delivery. So that was in Professor Andrew Tsourka’s lab at Penn, also in bioengineering. And that was when I was like, okay, I’m really interested in delivery of therapeutics. That seems very cool. Like designing these nano medicines.

And so that was kind of what’s spurred me towards where I am at my PhD today. And so when I was applying for PhD programs, I specifically was looking at like drug and gene delivery groups. And so I applied to, I think, eight or nine schools across the country. I didn’t have a strong preference towards where I wanted to be other than pretty much either east or west coast. I didn’t really want to go in the middle of America for whatever reason, so I did east or west and ideally either close ish to home, so I applied to like University of Maryland. I’m originally from Baltimore and also applied to Penn because I was already there, and Yale, Cornell, and Columbia, because those were all kind of like geographical areas I could picture myself living in and I do think I’m getting a little off track now, but I do think that’s an important consideration to keep in mind is where you want to spend the next four, five, six years of your life, because that is a huge chunk of your life.

So you want to make sure that this is like a place that you can really see yourself building a happy and sustainable lifestyle at. So yeah, I applied to a bunch of those schools, got into a bunch of programs, which I was really excited about. And I think when you’re interviewing, you’re also looking at not just like, am I a good fit in this lab, but are they a good fit for me?

So kind of matching two puzzle pieces together. So then I found professor Leong, Kam Leong’s lab at Columbia, and he did specifically drug and gene delivery, which is exactly what I wanted to work on. He said, you know, if you join my lab this is the project I’m thinking you could work on.

And it was, specifically gene editing in the brain, which I was so, so like, just you know, taken aback and like amazed by, I thought that was such a cool idea, cool project. And I knew that it was to target Alzheimer’s and my grandfather actually started suffering from early onset dementia at the time. So I was like, okay, this is super meaningful to me as well. So I decided, this is a research direction I would be really excited about, really passionate about. And I also could see myself living in New York. I had a lot of friends that had moved here. So I was like, okay, I think this is the one. So that’s how I ended up here today.

[00:10:12] Jon: Yeah. No, that’s amazing. I will definitely like to get into your you know, your, your research, Before that, I’m actually really curious about your experience in New York these past five years because you did mention that, you know, a big part of a PhD is that you’re gonna be there for five years and living there is obviously an important consideration.

And so now that you’ve been here for a considerable amount of time. Do you think you can reflect back on, on your experience these past five years what that’s been like for you?

[00:10:45] Sarah: I think one I love New York, I didn’t come in knowing that I was going to love New York. I was a little overwhelmed by it. I actually didn’t apply to any schools in New York for undergrad because when I first visited Columbia back in like, I think it was 2013 or 2014 when I was looking at schools for undergrad I was like, Oh, it’s nice.

But New York is such a crazy place to be. It’s like so much stimulation. And there’s not a strong, like campus feel just because you’re in the middle of. one of the world’s biggest cities. So I kind of for undergrad was hoping for something more with the campus feel. So that was, you know, one consideration.

But now for grad school, I think New York is such a wonderful place to be. And I think especially in your 20s, when you’re kind of going through a lot of changes and, you know, Growing with your friends, trying, becoming a real adult. I feel like leaving college is a step towards becoming a real adult.

And so I feel like it’s such, it’s been such a wonderful environment for me because one, it’s just so culturally diverse. I, I really love that about New York. I think, you know, going to different visiting different cities across the U S and also across the world, you don’t really get this many. People of different backgrounds in one city in such a concentrated sense.

And so I think that’s been really eye opening and really wonderful. And I do think because it’s so busy and like there’s always something going on that you’re never bored. So every weekend is like jam packed with things to do. If it’s not already consumed by research. And so I think it’s, it’s been like, yeah, the kind of the perfect place in my opinion, at least to do a PhD and to kind of also be spending your, your early twenties, mid twenties.

[00:12:29] Jon: Yeah, I love that. And it sounds like it’s going really well for you with the, with the, with the choir and also all the music and artistic outlets. The next thing I sort of wanted to get into is, Yeah, the research, the research side of things. So you, you did mention that you are in Kam Leong’s lab at Columbia.

And the main research topic is regarding gene editing in the brain and Alzheimer’s and specifically targeting Alzheimer’s. It’s really cool that you’re sort of able to implement this more clinical aspect. Sort of re circling back to your original interest about being a doctor. And so I’m really curious about sort of your, your timeline as a PhD student.

So maybe you can lay the groundwork for us and talk about I guess generally these past five years.

[00:13:22] Sarah: So, right. I think the broad overarching goal of my entire PhD has been gene editing in the brain, but I took a lot of side projects and side routes along the way. And I think Lucas mentioned this too is that life is or life as a PhD student is very much a roller coaster. So you’re always going to have a lot of ups and downs and you have to just come to come to terms with that, be at peace with it and like be along for the ride.

So I think I didn’t start out doing exactly what I ended up proposing in my thesis. Actually, I started out our lab to kind of give you a bit of background. Professor Leong kind of is interested in three broad directions. So one is tissue engineering, and then one is drug delivery and one is gene delivery.

 I think for tissue engineering that would be more like organoid development, I’m less familiar with that arm of the lab so that’s one completely separate portion of people that work on that. And then there’s drug delivery, which is going to be more related to like delivery of small molecule therapeutics.

And I think that has some overlap with the gene delivery group because both are kind of designing these delivery systems just for different types of cargo and for different applications. And the drug delivery portion, the part that he’s particularly excited about is this term called scavenging, which is immunomodulatory materials that will kind of through their immunomodulatory effect to be able to have this kind of therapeutic function.

As a carrier itself on top of the cargo that it’s delivering. So that’s another aspect. And then my portion of what I worked on in the lab is gene delivery and gene editing. So we looked at delivery of Not just like CRISPR systems, but also Cree recombinase systems for both non viral and viral delivery.

And basically I came into my PhD starting on this project that’s this five year huge NIH grant that’s collaboration between both our lab and then Professor Elisa Konofagou is lab also in the BME department at Columbia. So our lab was responsible for the delivery aspect and then the Konofagou lab was responsible for how do we bypass the blood brain barrier, because the major challenge in delivery to the brain is the blood brain barrier which normally protects your brain from pathogens . basically what their lab has innovated on is this system called focused ultrasound or FUS for short.

So they have these abbreviations for basically ultrasound technologies that are meant to open up the blood brain barrier. And they’ve also applied it to other applications, but for this project it was, you know, to overcome the major challenge in brain delivery, which is the BBB.

And so what happens is we co deliver a micro bubble along with the therapeutic and also the ultrasound stimulation, and then under ultrasound the microbubbles will cavitate and push against the blood vessels and open up tight junctions in between endothelial cells in the brain capillaries. And that allows the co delivered drug or therapeutic whatever to pass through.

So, that’s a major innovation and non invasive delivery. And. Because traditionally, what people would do is you’d go through intracranial surgery, so we just inject things directly into the brain. That’s kind of, I think, the only effective way to deliver things to the brain currently. Or there’s things like actually, Professor Leong, many years ago during his postdoc, developed this novel technology called Gliadel, which is a wafer drug, controlled drug delivery system that you implant in the brain for controlled release of a glioblastoma drug.

So, but all of those require brain surgery. So this is kind of an innovation in the field to have this non invasive and temporary opening of the BBB so that you can deliver drugs systemically, which is preferred for patients, obviously. And Then you can get it to the brain eventually. So that’s a cool technology and we capitalized on it by delivering both viral and non viral systems.

So my first, my very first year when I joined the project was already underway in the viral portion. And so the postdoc who was mentoring me Dr. Sima Lau, who’s now a professor at the University of Buffalo. He was developing an AAV, or adeno associated virus, specifically AAV9, which has brain tropism to deliver CRISPR components to the brain with FUS.

And then what the second portion of the grant proposal and the portion of the project I was going to be working on was delivery of polymeric systems. So there is a technology that’s been in the lab for a while, a chitosan PEI polymeric delivery system. And that was originally used for oral gene delivery, but because In the literature, there’s some signs pointing towards the fact that chitosan can permeate tight junctions.

We thought, okay, this could be a potential a good delivery system for delivery to the brain also. So I spent my first year basically getting up to speed on gene editing, which I had zero experience doing. And I also want to kind of throw in for as advice for younger students that you do not have to pick a topic that you’re like very familiar with. Let’s say you’re like a neuroscience major and you suddenly want to pivot towards like tissue engineering of the knee or something. I don’t know. That’s obviously like big pivot, but you could do it. Like, I don’t think you need to come in with the rights research skillset per se, in order to succeed.

You just have to be driven and interested and passionate about the topic. So I had no experience in gene editing, but I thought it was super cool and I really wanted to learn about it. So I spent a lot of hours in my first year. In the lab getting up to speed on, you know, how does CRISPR work and how do we design these like guide RNA systems?

How do we evaluate gene editing from tissue samples? All of that. So you, you will learn it all on the job and you will pick it up fine as long as you’re motivated to do it. And So that was my first year. And then also a lot of it was polymer synthesis, which I was also only like a little bit familiar with because my previous drug delivery lab was doing iron oxide nanoparticles.

So very different synthesis process. But all of that to say, it was a really great learning experience. It ended up the polymeric system ended up not working in vivo. And you know, I can go into the reasons why and all of that, but basically I decided. Actually, when we realized that it wasn’t working very well, that was when COVID hit.

So then I spent three months at home because we were kicked out of the lab. We weren’t, you know, we didn’t have access at all. You just had to like suddenly stop all of your experiments. I think we were given one week’s notice by the school to like freeze down our lines. But any like really, really important animal experiments, and then lab went into total shutdown.

And so that was, I think, yeah, 2020 March, I believe. And so when that happened New York was also like kind of crazy cause it was an epicenter of it the pandemic starting to happen. And so my parents were like, please come home. Like, we don’t want you to be in New York. So I ended up going home for three months and then came back to New York in June or July of 2020 and tried to like restart things, but that was really hard because everyone was trying to adjust to this new normal and like, didn’t know what to do.

If we weren’t able to go into the lab and also had to continue research in this very different manner. So I spent a lot of time during those three months thinking about how I could, like, save this project or, or come up with a different way to approach the project because basically the Polymeric system was very toxic in vivo.

So, you know, it worked great in cells. We saw gene editing in cells, but then as soon as we took it to the doses that are required for systemic delivery for the mouse models that we were using. It was just too toxic. And so I was thinking, okay, what can we do? What can we do? And then around that time, the COVID vaccine came out and that was like the huge advent of lipid nanoparticles.

And everyone was obsessed with lipid nanoparticles. So I thought. Why don’t I try that? Because I’m trying to deliver nucleic acids. And that’s exactly what the COVID vaccine was, was mRNA delivery of lipid nanoparticles. So I was like, Okay, let’s, let’s see what I can do with that. I looked into labs that had expertise doing lipid nanoparticles and then reached out to a lab at Hopkins that had a library system.

So they had developed this library of over 1000 formulations just by modifying the ratios of each of the components in the lipid nanoparticle. And the interesting idea, I was brainstorming with the student who was working on this after I got in touch. I said, do you think there is a way that we could screen for brain tropic or neurotropic lipid nanoparticles within this library?

I’m sure not all of them work well in all cell types. So what if you screen this in like all the different cell types you have, and we look at ones that are specifically highly transfecting neuronal cells, but maybe not up their cell lines and everyone loved that idea. They thought it was really interesting.

So we went forward with that and then tested a few lipid nanoparticles in Intracranial delivery first. I think one thing I learned from my first two years was just like You cannot go into a project thinking you’re going to achieve that huge goal immediately. You kind of have to, I think, to set yourself up for success.

It’s good to have smaller milestones along the way. Like I’m going to achieve this small thing first. And then the next small thing first and keep building on that before you can get to the end goal successfully. So that was one thing I learned from, you know, all the different scramblings that I did in my first two years.

And so I thought, okay, before I tested in The ultrasound system. Let me just see if it can actually edit cells in the brain. If I just directly injected into the brain. So actually, not many people had even done that before. And so we screened a bunch of different clusters of nanoparticles by injecting them directly into the brain and saw that a lot of them actually do work really well.

And that was really exciting. That’s going to be a manuscript that I hope will come out within the next year. But that’s, yeah, that’s kind of the genesis of the work. And then Hopefully we’ll then take that to focused ultrasound mediated delivery, but all of that to say, I think my Ph. D. was very nonlinear.

It was like starting on one thing, ending up doing something very different, even though it’s still towards the same goal. It’s like a complete, technically completely different delivery system. And so I think what I learned in that process was just. One learning how to set yourself up for success by having smaller, more achievable goals.

And then second, to be open to pivoting and be open to changing directions. Because that, that definitely, I think, is a, it’s a huge part of your PhD. Not thinking of it as like a sunk cost, but more so as an opportunity to try something different and to, to learn something new.

[00:25:01] Jon: I think research especially is unexpected. And there’s a big serendipitous aspect of research as well. And I love how you sort of came to your end goal. One thing that’s sort of fundamental to all research experiences is mentorship. And so I’d love to hear about your relationship with Dr. Leong and, you know, how he supported throughout these past five years.

[00:25:27] Sarah: Great, great point. I think mentorship is actually probably, if I were to pick the most, most important thing to success in your PhD, it would be mentorship because no one does these huge projects alone. It’s, It’s just impossible to like be doing this independently and come up with a solution by yourself.

So you really need the right mentors and also the right mentees and people just like community supporting you. And so that starts with your research mentor. For me, that was Dr. Leong and he is just such a venerated expert in the field. So I was already drawn to that. And every conversation I had with him is like this very in depth research conversation of, you know, okay, understand.

Understanding like he’s not necessarily going to sit there and help me troubleshoot my experiments. It’s been like decades since he’s been like in the lab pipetting, but he is very much a source of inspiration and kind of brainstorming friend and mentor to go through like, okay, how do I pivot from this project or what are some of the different things that I can try on a large scale.

And because he’s so busy with a lot of other things, generally we meet with each other like once a month. And so I think that’s very different from other mentors who are maybe more hands on. He’s a very like hands off mentor in the sense that he really trusts the students to just, you know, once he gives them a general direction to get it off the ground and get it going and like he’s always available for you to reach out to him, but I don’t think he’s the type to like check in every week and be like, hey, what’s happening? So I think for me that works. I don’t know that that works for everybody. I do think At times I I did wish like, okay, I wish you know, he wasn’t traveling for two months because He was invited for talks all over the world and like I wish he was here so that I could talk to him so that we could figure out what was happening with my project.

But there were other times where I was really grateful for the space. I’ve heard some of my peers complain about, oh, my mentor is like checking on me every day or checking on me every week, like asking where my data is. And I think that can also be suffocating sometimes. So it’s, it’s a fine balance. And I think you have to really understand what works for you. And the only way you can do that is by getting research exposure and meeting a lot of different types of mentors to try to get a sense of like what mentorship style fits your working style the best. And then I think besides your key research mentor, the reason his hands off style worked for me was because I had very hands on mentors in lab. My first year, especially when I knew pretty much nothing of what I was supposed to know. My mentor, Dr. Lao Sima was really like patient with me and taught me pretty much everything from like zero to 100. And so I was really, really grateful for that.

And then beyond that, just like building up basic research skills was finding good collaborators who can be good mentors to you as well. So, Professor Konofagou is an expert in something completely different and I needed their lab’s expertise. I talked to a lot of their students on a very regular basis to try to understand, like, how does the ultrasound system work and how do we use that to our advantage.

And then with the intracranial project, that one I want to highlight because I met this MD PhD student in their lab. That’s professor Qi Wang’s lab also in BME at Columbia and his lab focused on like neuromodulatory behavior, understanding of that. And so more basic neuroscience stuff, but there is an MD PhD student in their lab, Cody Slater, who has just been the most wonderful mentor because He taught me how to do intracranial surgery from scratch.

That was something I was like, never in a million years did I think I was going to be doing brain surgery in mice. And so, you know, that too, for me to overcome that barrier was. It’s really difficult and I think he was super patient and super kind and teaching me all of those things and also just such a wonderful person to bounce ideas back and forth off of.

You know, we talked about like, okay, once we get to this step what’s the next best thing to try and what if we did this or what if we did that? And I think you really need people in your research life that can do that for you because if you’re just kind of internally independently thinking all of these things, it’s really hard to get things off the ground.

So you really need someone to kind of be a bouncing board off of and to, to tell you like, Oh, when that, when that’s a good idea and when that might not be such a good idea. So I think, yeah, having good mentors, having good collaborators, colleagues. And then I think the last aspect is having good mentees.

So I had incredible undergrad mentees I worked with for, I think, starting my third year, I started working with both masters and undergrad students. And particularly last summer, I worked with two amazing undergrad students who are now going to start, both of them are going to start their PhDs. I’m so proud of them, but they worked really, really hard on the intracranial project I mentioned.

And you know, it could not, it could not be at the stage that it is now for ready for a manuscript it without them. So I think it’s also being open to mentoring students and paying it forward and finding good students to, to kind of help you with your work. And I learned as much from them as they have from me, I think.

[00:30:56] Jon: Yeah, I, I love that sort of highlighting the fact that this is all a team effort and not only do we stand on the shoulders of giants, but, you know, we, we have the help from, from other people to get us to where we are today.

Um, aside from mentorship and how that supported you throughout your PhD.

Another aspect is just sort of the program itself. So bioengineering maybe you can talk us through your experience with just the program as a whole.

[00:31:25] Sarah: Yeah, definitely. So I think Columbia BME is very unique in the sense that we have professors who are kind of their leading experts in their like respective niche field, but it is quite spread out we don’t have. And I guess this maybe isn’t necessarily unique to Columbia a lot of schools do follow this model of. You don’t want to have too many experts in one specific area. So you kind of draw people from many different fields, and they’re all at the top of their areas. So for drug and gene delivery, I think it’s really just Professor Leong and maybe one or two other professors now who are newly joining the department.

There’s Professor Ke Cheng and Professor Santiago Correa. Professor Tal Danino does delivery but with bacteria specifically. So I think, you know, having all of these experts in one area, but then also in many other areas, like there’s, I mentioned Professor Konofagiou, who does ultrasound. So this project could not have worked without their labs expertise and Professor Qi Wang, who does like intracranial delivery.

So that’s, you know, many different types of experts coming together. And then, I think the other aspect is the being open to collaboration and like creating this fertile environment for collaboration. So you know, you may have, maybe many programs have experts in different areas, but bringing them together to work on interdisciplinary projects, I think is very important as well.

 So I guess the other aspect of like my experience in the department is that our lab is on the medical campus. Being on a medical campus is nice because we have a lot of like cross collaboration with clinicians . And there was one project I worked on that was with Professor Steven Tsang, who’s an MD PhD. And so his lab special specializes on gene editing in the eye. And so that was like looking at delivery systems to the retina, which was really interesting and, and very different as well. And so I think those types of collaborations couldn’t happen unless you’re in an environment that has, you know, both the medical school and strong research university and also the interests across different, different labs and professors to want to connect and collaborate with each other.

But so the medical campus and the main campus are actually quite separate in their own ways. They’re separated by about 50 blocks. So maybe 70, 30 split of labs in the department on the two campuses so I feel like I’m relatively close to the people in my lab and also people in other labs on the medical campus. But I do feel a sense of removal from the most of the other labs are on the main campus. And so that’s been an interesting dynamic to kind of navigate and I think you do have to just be more present and be more involved with things happening on the main campus.

If you’re on the medical campus in order to bridge that gap, but It’s not, it’s not impossible, not particularly difficult. And there’s always a lot of events that the department organizes to kind of facilitate those two different campuses, especially now that I think we’re having more and more BME labs actually move to the medical campus. So that’s been really, really fun.

[00:34:44] Jon: Yeah, that’s awesome. I think that can definitely help with sort of meshing people together that normally wouldn’t mesh, outside of outside of research. I, I think that’s an interesting point also that you highlight about the separation perhaps between the medical campus and, and the just the main campus itself.

I was curious on sort of, You know, the, the, the events that they hold and maybe your experience with them and how effective perhaps that that has been and sort of, you know, getting yourself out and seeing new people.

[00:35:17] Sarah: yeah, definitely. So we have this organization called GO BME, which I think stands for graduate organization of BME. Basically, and I, I think that’s something that exists across most schools as well, or most BME programs, but basically they’re kind of the ones in charge of facilitating like social events for the department for grad students.

And they do a lot of like Cross department events too. So, you know, they’ll host like Oh, Mech-E and BME happy hour or something like that. And then we’ll meet at a bar, like somewhere it’s still closer to the main campus, but it is like somewhere in between the two campuses. So I do feel that that’s like them making an effort to kind of bridge that gap.

But I think I personally live close to the main campus too. So that’s easier for me to kind of get myself to main campus and like, see people catch up with my friends there. And go to the events that they host on the main campus, but we also have events on the medical campus. So I think every other week or maybe once a month, there’s like bagels and coffee hosted by the department.

And so that alternates between main campus and medical campus. And so, I mean, usually it’s the people that work on the camp, that campus, but everyone’s welcome. And like people will come from other campuses to kind of catch up with each other. And I’ve met a lot of other PhD students that I might not have cross paths with who work in different labs and very different types of research.

And so I get to know them through those types of events, which is nice.

[00:36:55] Jon: Yeah, no, that, that sounds really fun. And it sounds like your entire graduate school experience has been just really amazing and really fulfilling. Looking forward now,, I’m curious on sort of, you know , how you will take your training here and apply that to your career endeavors. And so maybe you can provide us with sort of a timeline and you know, what you hope to accomplish in the next, maybe one, five or 10 years.

[00:37:21] Sarah: Yeah, awesome. I think this is a great thing to talk about too. And I’m glad you brought it up because it’s something I’m is very much on my mind right now because I am applying for jobs. I’m graduating this May. So in, in actually two weeks, so I really have to, yeah, figure out my next steps. And so I think I’ve always had a more fluid approach to , my career path and also.

I’m not really the type of person that plans out really far in advance. So when you asked me one, five and 10, I think I could answer one in five, but 10 to me, it’s like this nebulous, I have no idea and I’m fine with that. So I think for me, I know that. I find a lot of fulfillment in building things, designing things, doing problem solving of like , challenging problems, but that can show up in many different forms.

And so one thing I didn’t talk about before, but I actually did a minor in engineering entrepreneurship at Penn during undergrad. And That’s, I think it was a minor program that was started at Penn, but now it exists at a bunch of different schools across the country, but basically what it is, is like, how do you apply and sharing concepts and also maybe bench work to translation and towards like a more business oriented lens.

And so that was really eyeopening for me. And. I learned a lot of like, you know, how do you start a company and how do you value a company? And how do you take your technology from like the lab to the clinic to patients? And all of that.

And so that was when I decided, okay, I want to look into maybe the, the marriage of both business and by medical engineering. And so I pursued internships in consulting and also at a startup, a medical device startup. So one summer I did this medical device startup is called OccuFlow. I think now they’re changing their name to OccuPulse.

So regardless what their devices is this Composite ocular blood flow analyzer. So essentially most of your blood flow. Most of your blood flow cannot be captured by conventional like devices that are used in an ophthalmology offices. And so what this new device would do is it would capture not only Your ocular blood pressure, but also ocular blood flow and up to specifically it analyzes colloidal blood flow.

So like up to 90 percent of your blood pressure and blood flow, which is a huge improvement and able to help importantly, able to help clinicians diagnose blinding eye diseases much earlier and to detect them much earlier. So that was really cool work, but. You know, I helped out with pretty much everything because it was so early stage.

So I was the only intern, first and only intern at that time. I was working with the CEO and the key the chief engineer to design the device, like solid works, renderings. And then like, I worked with like the FDA expert to figure out how we could get through FDA 510K, which is the pre market notification approval process.

And then Yeah, that kind of like opened my eyes to, okay, this is how you actually start a company. And this is how you would get a device from literally like drawings, like not even existing yet to building it and then getting it into a doctor’s office. So that was really, really cool to me. And then I decided I wanted to get even more business exposure.

Cause I felt like that was the part I was missing. I was like, I know how to do research. I know how to do science, but like still feel like all of this business stuff is very new to me. Very like difficult to grasp for me. And so I ended up doing that consulting internship in life sciences consulting specifically.

So that was helping a big pharma client figure out which indication they should prioritize. But that was really cool to me that you’re applying the same problem solving mindset and like logical thought processes, but to a more like business oriented application.

So those experiences kind of shaped my view of, I came into, I think this is a bit unconventional, but I came into my PhD knowing I didn’t want to do academia. I think the main career paths that come out of. Bio and sharing are either, especially a PhD or either academia or industry. And then maybe more non conventional would be consulting and finance.

And so I knew I didn’t want to do academia mostly just because. I love the mentorship and teaching aspect of it, but I knew that I didn’t want to run my own lab. I thought that was just not along the lines of what I could picture myself doing. So I knew I wanted my PhD experience to be more geared towards learning these like problem solving skills and team management skills, and then taking that towards a more like business oriented application.

And I think a lot of these jobs do require PhDs. So I knew, you know, this was also something I just had to accomplish in order to kind of go further in my career. And so now that I’ve kind of come full circle, I’m like reconsidering consulting within consulting, there’s management and life sciences, boutique consulting.

So management consulting is more geared towards like, broader, more large scale problems that can be applied to many different types of companies versus life sciences would be like specifically I mentioned I worked on like indication prioritization projects. So, you know, more specifically for like either pharma or med tech companies and helping them like, bring their, bring their products or portfolio pipelines to the clinic.

And then in terms of like finance, I also started thinking about equity research and healthcare investment banking is another aspect, although I know I don’t want to do that. So I think there’s a lot of like, different things and really endless opportunities that I could consider, but those are kind of the key areas I’m thinking about.

And those are the ways that the things that have informed my decision making on, on those different paths as well. So I think in a year, I’m just hoping I’ll be able to start at one of these types of companies, whether it be in management or life sciences, consulting or equity research, whatever that might be just to gain more business experience.

And then in five years, hopefully be working really feeling comfortable with that type of work and being like an expert in that. That’s like the same amount of time it took me to be an expert, quote unquote, in that gene editing, I guess. So yeah, I think that’s like where I see myself progressing.

But then in 10 years, like I said, who knows, I, I’m kind of more like a go where the road takes me and not necessarily planning every single step ahead. So yeah, I think I’m, I’m open to whatever happens in the future, but I, I’ll probably have to reevaluate at the five year mark what I’m gonna do in the next following five years.

[00:44:23] Jon: Yeah. And also just the fact that Maybe anything outside of academia is maybe less, less certain. And so ten years down the

[00:44:32] Sarah: Yeah,

[00:44:33] Jon: who, really does know, you know

[00:44:35] Sarah: Exactly.

[00:44:36] Jon: but yeah, I do like this sort of unconventional aspect of, of, of, well, I think I like this unique aspect of, of a Ph. D. and the fact that you can do anything with it.

And perhaps maybe you can end us with, Just looking back do you have any general advice for those listening and for perhaps those interested in PhD?

[00:44:58] Sarah: Yeah, definitely. I think the things I probably wanna leave listeners with is. The major lesson I learned during my PhD is to don’t be afraid to try new things and to pivot. So I think that’s like a key message I want to leave everyone with is that You can’t always predict the future, but you can create it.

And so, despite not knowing, you know, having this uncertainty of, are things going to work you can set yourself up for success in the way you design an experiment, in the way you plan for, you know, each milestone that you’re hoping to achieve. And When things don’t work, I think you have to be very open to the idea that, yeah, that’s normal.

And I need to figure out, you know, how I can re redesign what I’ve thought. And also be open to trying a completely different thing that you might not have been open to originally. Like I mentioned, I started out with polymeric delivery and I ended up with lipid nanoparticles. So that’s, you know, Very perhaps unconventional.

And then I think the other thing is to be able to seize good opportunities when they come to you. So, you know, when I had the opportunity to work with Cody, I jumped on that because I, I knew like I could tell from my first meeting with him that, He was this incredibly motivated and driven and just like very kind person.

And so when you meet people like that, don’t let them go. You know, really, I feel that I’ve like definitely taken advantage of Cody’s time, but I made him teach me intracranial surgery and I, you know, really forced him to be a collaborator on this and it’s worked out wonderfully. And, and he was super excited about the results that came out of our project.

And now he’s thinking to take it in a different direction as well. So I think, yeah, being open to two new things and then seizing good opportunities when they come to you is very important. Finding good mentors is very important. And then paying it forward and finding good mentees and helping them find their career paths is also very fulfilling, not just, you know, an important thing to do, but you’ll find fulfillment in that as well.

And I think in terms of like specific PhD advice, it’s just make sure you find the best fit for you. So really like don’t just think of it as an interview process for yourself But it really is about finding the right fit and like asking, you know Can I see myself here for the next five years of my life or maybe longer?

because It is kind of a really important part of your life, you know, from maybe 21 to 26 27 whatever that might look like. And there are people who come, you know, go work and come back and do it later but regardless five years is not a short amount of time, and so you really want to make sure you can picture yourself working with the people in the lab working with your mentor and also just living in the city that you’ve chosen to live in. So, yeah, those are, I think, the things I want to leave behind.

[00:48:04] Jon: Thank you so much for tuning into this episode of the People of Science podcast. For summaries and transcripts and how you can get in touch with our guests, navigate to the episodes page on my website at peopleofscience. blog. Hope to see you in the next one!