885: Studying How Physical Forces Shape Cancer, Immunity, and Disease - Dr. Meenal Datta

Welcome and sponsor introduction

0:00Hello, everyone, and thanks for joining me today for episode 885 of the People Behind the Science podcast. I'm your host, Dr. Marie McNeely, and I'm excited to be speaking with our guest, Dr. Minaldata today. This episode is made possible with support from our sponsor, Innovative Research. Listeners, Innovative Research has provided scientists with quality lab products made in Novi, Michigan for more than 20 years. Their portfolio includes human and animal biologicals, assay and ELISA kits, antibodies, and more. Products can be purchased

0:32directly from their website by credit card or purchase order at www.innov-research.com. That's www.innov-research.com. They offer small quantities, bulk purchases, and custom orders. From human whole blood to specialized antibodies, Innovative Research has what you need to succeed in the lab. And today, Meenal has some great stories to share with us about her lab and her life. So get ready to meet another one of our amazing people behind the science.

1:04Every day, discoveries are made that will change our understanding of the world around us. Dr. Marie McNeely is here to bring you the brilliant minds who are making these discoveries so they can share their incredible stories and take you on an amazing journey. Welcome to People Behind the Science.

Meet Dr. Meenal Datta

1:28Hello, everyone, and welcome to People Behind the Science. Today, I am thrilled to be speaking with our guest scientist, Dr. Meenal Datta. So, Meenal, welcome to the show today. How are you? Thanks so much for having me, Marie. Doing excellent over here. Well, we're so delighted to have you here with us today and to learn more about you and your work. But first, Meenal, let me take a moment to introduce you to everybody. So, listeners, Meenal is the Jane DeFlorio Collegiate Professor of Aerospace and Mechanical Engineering and Associate Professor of Aerospace and Mechanical Engineering at the University of

2:01Notre Dame. She received her bachelor's degree in chemical engineering from the University of Massachusetts Amherst and her PhD in chemical and biological engineering from Tufts University. Meenal conducted a postdoctoral fellowship at Harvard Medical School and Massachusetts General Hospital before joining the faculty at Notre Dame in 2021. Now, she's been recognized with an NSF Career Award, the CMBE Rising Star Award given by the Biomedical Engineering Society's Cellular and Molecular Bioengineering Special Interest Group, the Rita Schaefer Young Investigator

2:34Award from the Biomedical Engineering Society, the Air Force Young Investigator Program Award, the Cellular and Molecular Bioengineering Young Innovator Award, and the Maximizing Investigators Research Award from the NIH. And today, Meenal, we want to get to know you both as a scientist and an engineer, but also as a person. So can you tell us what do you like to do when you're not working? I like to go for walks. We have really beautiful campuses here at Notre Dame and at the nearby

3:04colleges like St. Mary's College, which is close by to us as well. So usually that's where I'll do all of my listening to podcasts and audiobooks is on a nice long walk. I used to do that on my commute in Boston, but now living in the Midwest, it only takes five minutes to get anywhere. That's when I usually get in my listening time. I also I've been sort of recreationally rowing since high school, actually. How cool. I picked this up again when I was a graduate student in Boston. And then when I located to South Bend to start my position here at Notre Dame, I was delighted to see that they have

3:40a South Bend community rowing club. So we meet a couple times a week and go out for a row on the St. Joseph River here, which has plenty of bridges and bends, as you can imagine, from the name of our town. South Bend is actually named after a bend in the river. So that's what I do outdoors and then indoors because, of course, we are exposed to a winter climate here. I like to read. I like to cook. And of course, I like to watch things as well. So I typically will put on something sci-fi or

4:11true crime related at the end of the day. That's usually how I relax. Fantastic. Well, it sounds like you've got a lot of cool hobbies and things that capture your interest. And you mentioned reading. We love talking about books on the show. So, Meenal, do you have a favorite book that you've read at some point or even one that you've read recently that you really enjoyed that you think our listeners should check out? As you can imagine, and I'm sure it's the same for you, Marie, it's almost impossible to pick a favorite. They change what seasons or I might even think back to books I read as a child. I'll pick a

4:42recent favorite. Over the summer, I listened to the audiobook for Everything is Tuberculosis by John Green. You may have read this as well, and I'm sure you've had guests who work in this area. Actually, my PhD work was largely in the field of tuberculosis. And now that I work in cancer, I don't always have a chance to visit it again. So this was a nice excuse to do so. And I really enjoyed it because I think John Green, who's known mostly for writing young adult fiction novels, really has a knack for this nonfiction writing. And he displayed very nicely through storytelling that

5:16our inability to curtail this disease that affects a third of the global population is really less about scientific losses or gaps and really more about societal or economic decisions. And so he takes us through both the history and sort of the modern reality of TB. So I enjoyed that a lot when I listened to it. Well, fantastic recommendation. And listeners, if you haven't read it yet, Everything is Tuberculosis or listened to it, I think this is a great recommendation. We will put it on our website for our listeners to find. And you hinted a little bit at what your research is

The physics of cancer

5:51about, but I'd love to dive into some of the details here. So, Meenal, how do you describe what you do in the lab to someone who's outside of your field or outside of science? The most basic explanation that I give is that I study the physics of cancer. And I know that that can sound a little bit as a misnomer to people who are outside of this field, but actually engineers such as myself have been taking these more hard science and engineering-based approaches to the human body, to our diseases, including cancer for decades now, maybe even a hundred years at this point.

6:26So really what we study in my lab is the fact that as a tumor grows, a solid cancerous tumor, for example, in the brain or in the breast, it's exerting physical forces as it grows. It's pushing on the organ that it's sitting within, and it also pushes back inward on itself. So in our lab, we work to uncover what the consequences of those mechanical forces are when it comes to disease progression,

6:58treatment resistance, and then also the inability of the immune system to actually fight against those cancers. So my lab, we call it the TIME lab, T-I-M-E, and that stands for Tumor Immune Microenvironment and Mechanics. That's of course why we shortened it. That's a mouthful. And that's based on the initial questions that I had when I started here five years ago, which was, we have a basic understanding of these mechanical forces on the cancer cells, but what are they doing to the immune cells that are

7:29both in and around the tumor? That's really the most basic way that I describe my research. And more recently, we have extended our study of physics in the context of cancer to think about even larger forces like gravitational forces. And we actually exploit gravity to our advantage when it comes to the way that we study and develop treatments for these diseases. So I'm happy to talk about that with you today. Absolutely. And I'm excited to get into some of the details

8:00throughout our conversation and just thinking about how these forces can impact not only cancer, but how our immune system can respond to it, I think is a fascinating area and sort of a shift in how people normally think about cancer. I certainly hope so. I've been really fortunate to have paradigm shifting research modeled for me by my key and main mentors. And so that's a style of science that I really wanted to adopt when I started my own lab. Absolutely. And let's talk about what motivates you in your own lab. You know, I think as a scientist, there are difficult times that you face, but we love

8:32to keep people motivated and inspired on the show by sharing quotes or sayings or things that can just sort help you get through the day. So do you have a favorite quote or a saying or just something that really motivates you? At the moment, there is a quote that I've been hearing repeatedly. And that has to do with the work I was just hinting towards. We've started to do cancer research in the microgravity environment of space. And in being exposed to the space industry, to the space research community, a phrase that I actually can't attribute to anyone, so I apologize. But a phrase in Latin that we hear often is ad astra

9:08per aspera, which roughly translates to, to the stars through difficulty or adversity. I think that's just such a lovely concept. And I think it can easily apply to your everyday life, regardless of what you do in your career or in research like ours. So I've been ruminating on that phrase for the last couple of years. Wonderful. What a beautiful quote. Well, we will definitely add this to our website for our listeners as well, if they're looking for a little motivation and inspiration. And you mentioned earlier that you've had these great mentors who are doing paradigm shifting work. And I think these

9:40mentors and role models and just inspirational figures can have a tremendous impact on your career. So can you tell us more about the people who helped shape you as a scientist?

Family background and early research

9:49The first people who shaped me were my own family. I was really fortunate to grow up in an academic family. Both of my parents are retired at this point, but my dad was a professor of chemical engineering and my mom was an elementary school teacher and then later a principal by the time she retired. So academia was part of the bread and butter of our family life. I remember hearing discussions of their careers and of their work days every night at the dinner table. My mom telling

10:20some funny story about a goofy kid in class or some entertaining exchange she had with a flustered teacher. My dad would come home and talk about winning a grant or not winning a grant. I even remember my parents speaking early about the tenure process and all of that as well. And the other thing that was really modeled for me at a young age, in addition to academia and teaching, was the STEM fields. My dad was a professor of engineering. My sister became a chemical engineer. I became a chemical engineer. So we sort of followed in that family

10:52footsteps. But I also knew from a young age that I was very interested in medicine and in the human body. As a child, I actually thought I would go to medical school. But once I made it to my undergraduate career at UMass Amherst, I was introduced to undergraduate research. So I performed research with Professor Susan Roberts, who was there at the time. And she had a very interesting bioengineering-based approach to regenerative medicine. And the project that I worked on

11:24was on encapsulation of cells for transplantation. For example, the specific project I was working on was encapsulation of pancreatic islet cells that you could implant into a patient with diabetes, for example, in order to treat their disease. Now, of course, this was all very theoretical at the time. That would have been the end goal after years or decades of research. But in my own small way as an undergrad, I contributed to that project. And that was really what turned me on to this idea

11:57of graduate school and a research career instead of practicing medicine. And it was that first experience with undergraduate research that really led me down the grad school path. That makes sense. And you mentioned you did your undergrad at the University of Massachusetts, Amherst. How did you then decide where you wanted to go and what you wanted to do for your PhD? A little bit of it was stochastic. So I graduated my undergrad in 2010. So there was still quite a bit of reverberation from the 2008-2009 economic crash, which at the time led a lot of students who weren't able

12:34to seek employment in the workforce. Instead, they went to further school. So there was quite a bit of competition for graduate school at the time. I frankly had a limited number of options of programs that accepted me into a PhD program. And that's really how I ended up at Tufts. It was one of the few that made me an offer, which was just the frank reality of the times. I have several of my own undergraduates who went through a similar time just this past year. And the one thing that I liked

13:05about Tufts, first of all, was that it was co-located in Boston. So it was surrounded not only by a really rich academic environment, but a biotech and pharmaceutical environment as well. And the other thing I liked is that the research topics of that department, chemical and biological engineering at Tufts, appeared highly diverse when I was applying as an undergraduate, ranging all the way from pharmaceutical development to treatment of cancer.

13:35Very cool. And for your postdoc, you, of course, stayed in Boston. Can you talk about that transition?

Navigating graduate school and finding a mentor

13:40This is one of those classic stories that I think is really useful to tell students. I think it's easy for them to look at professors like myself, maybe look at a biography and see this list of schools that I went to or see this list of accomplishments. And it looks very linear, right, and sort of planned out and straightforward and as though everything happened correctly and at the right time. But you and I know, Marie, as do so many people who are professionals in this area, that life is not a straight line. Things happen in these circuitous paths. And when I got to Tufts, I actually really had a tough time

14:14settling into graduate school. I think that even coming from this very privileged educational background where I thought that I understood what higher education looked like, what a research career looked like. But in reality, I personally had quite a bit of struggle moving from, let's say, the undergraduate class plus research model into full-time research. So I had some of my own detriments. And then I also was having a tough time finding a supportive laboratory and advisor to work with within my own

14:47department. I went through a series of positions and a series of labs. And after about a year and a half or two years, I was actually convinced at that point by some of the higher ups in my department that I should consider moving on into industry after a master's and that maybe research wasn't quite what I was suited to. And of course, at the time, I trusted these individuals who I respected and I looked up to and I admired. And I think we forget how young people are even when they go into graduate school, right?

15:20You're still often if you're a traditional student who goes straight from undergrad, you're still in your early 20s. You still have quite a bit of growing up to do. So I just didn't have the personal self-confidence at the time to think any differently that maybe I am cut out for research, but just not in this particular environment. So I was really almost on my way out of graduate school when just by chance, I was introduced to the person who eventually became both my PhD and my postdoctoral advisor.

15:51And that was Dr. Rakesh K. Jane, who was a distinguished professor at Harvard Medical School and at Massachusetts General Hospital. And through meeting him and through getting to know him, he was really willing to take a chance on me for reasons that I can't explain. I think you have to ask him. And we just started off small. We started off with a master's project that was sort of mathematically based. Then once that was successful, we moved into a full scale PhD,

16:21including experimentation. And from there into my postdoctoral fellowship as well. It was this relationship that started by chance, but really grew into what became the foundation of the way that I approach my career now. Absolutely. And I'm so glad you shared this story because I think so many people, if they don't find that fit, they are kind of turned off by research in the early years of graduate school. And I myself went through, I think it was five rotations before I finally settled in a lab. And you sort of feel like a failure at that point, right? Like, why can't I make this work? But what kept you going? What convinced you that you were going to give this another shot?

16:55I think it was really just, there was a couple key people who were still in my corner, including my family, of course, who would have supported me no matter what decision I made, whether to stay or to leave. But also a couple key professors on both side of this equation, both in my home department. And then of course, Dr. Jane over at Mass General Hospital. I think there was also a little bit of luck involved in that. He had a project and a position open, and I was a student ready to slot into that, which now being on the other side,

17:28I understand that that's often exactly how these positions go. Despite your best intentions and planning, so much of it is just left up to chance of when do you have an open position? When do you have funding for a particular project? And that's really how I got into tuberculosis. So if you'd like Marie, I'd be happy to tell you more about my mentor and sort of his approach and his lab's approach to research and how I got into these areas. Absolutely. So Dr. Jane is a chemical engineer like myself, and this might've been part of the reason that we bonded, but I think he's one of

18:01these exceptional examples of a person who over a 50 year career now has been able to transition from the very hard sciences at the bench all the way to the bedside, to the clinic. He took an engineering based approach to understanding cancer and launched a cancer lab at Mass General Hospital. But the project that I slated into was actually treating tuberculosis like cancer. And I know that might

18:32sound a little odd at first, but for anybody who's read, let's say everything is tuberculosis or similar, you might be familiar that one of the hallmarks of infection by the TB bacteria is actually you develop these nodules in your lung called granulomas. And his hypothesis before we had significant data to support it was that structurally and functionally, they would actually behave a lot like a tumor. The only difference was they would be made up of our local cells in the lung or of

19:07infiltrating immune cells from the rest of our body rather than cancer cells. So we decided to take an approach to understanding and studying and eventually overcoming those tissue abnormalities in those granulomas the same way that he had done for decades prior in cancer. Oh, that is so cool. And it sounds like he was a phenomenal mentor. And you mentioned his work as paradigm shifting earlier. And I think you're absolutely right. This is a major shift in how we could be

19:37thinking about treating infectious disease. In the context of TB, for example, there are so many amazing researchers who are trying to discover new effective antibacterials to kill the bacteria. Of course, ultimately, that's what you need, right? You need a drug that's going to destroy the pathogen that you're going after. But we were really focused on the engineering aspects of this problem. For example, can we even get the drug to the site of the disease where the bacteria are? Because you can imagine if these nodules are sort of like a tumor,

20:11they're large, they're thick, they're full of cells, they're full of protein scaffolding that these cells deposit. So it actually restricts drug delivery to the site of the disease. So I spent most of my PhD under the mentorship of Dr. Jane and the work that he had done in tumors to, for example, target the blood vessels and target that protein scaffolding in order to get drugs actually into those granulomas where they would reach the bacteria and be more effective. And the same can

20:44be true for cancer, right? You could design a blockbuster chemotherapy or anti-cancer drug. But if you can't get it to the site of the tumor, it's not going to be effective. That was the approach that he took and that he taught me to treating cancer like an engineer. Definitely. And this sounds like a really excellent training environment for you in this early stage of your scientific career. And I'm curious then about the next step. How did you find your way to Notre Dame ultimately?

Transitioning to Notre Dame during COVID

21:09This is another classic story of external circumstance. I totally agree with you. I was scientifically spoiled while I was at Mass General because I ended up spending over a decade with Dr. Jane in his lab between my PhD and my postdoc. And I was surrounded on the one hand by clinicians, by people actually doing this work so that when we made a discovery at the bench, we could translate it to patients faster, more effectively, talk to these doctors about these approaches that we had,

21:40explain these concepts that we can open blood vessels, that we can get drugs in, etc. That was just amazing, especially as an engineer, to be able to have that type of crosstalk. So we could easily spend a day where in the morning we would go to cancer grand rounds at 7.30 in the morning and in the afternoon we'd be at MIT listening to the next nanoparticle drug developer who had won a Nobel Prize, for example. So the environment was truly remarkable and I couldn't have thought of a better place to set up myself as a successful independent researcher as being in sort of that ecosystem.

22:15But of course, the way that I ended up eventually on the faculty market was because my transition period happened at yet another one of these periods outside of my control, which was March 2020. So we all remember, yeah, of course what happened. So all of a sudden, especially working at Mass General, where you can imagine there was a large number of COVID-19 cases and we were really restricted to key personnel and frontline workers, we had to drastically ramp down the experiments we were doing. And this was a lab that was routinely

22:50breeding and experimenting on thousands or tens of thousands of mice at a time. Oh, wow. It was really a huge endeavor, almost like its own company. And all of a sudden that work came to a grinding halt. So like a typical student, I had plenty of data that needed to be analyzed. So I took my time to do that and go through data analysis and work on manuscripts, things that have been sitting on my desk for a while. But I also decided at that point to go ahead and start writing my faculty applications for the coming fall. And that's exactly what I did. I prepped for

23:24these interviews and professor positions through the summer and then went on the market in the fall. And again, I think because this had been modeled for me at home and then I saw what in my mind was the best case scenario from my mentor really going from fundamental engineering to as close to a patient as an engineer could possibly get. Between these two examples, I had finally built the confidence to think that I could do this myself. I have my own ideas. I am a legitimate and accomplished researcher.

23:57And most importantly, that I could take these lessons learned and disseminate them to the next generation of scientists, use my own laboratory to train these people who would really push these cures and this research forward. It was a combination of finally, as a person, I felt ready to take that leap. And then externally, I sort of got shoehorned into that process in that moment. So how did Notre Dame emerge among the top of your choices? It was so interesting because I had decided, even though I'd had an amazing experience at Mass

24:30General, that I really wanted to get back to my fundamental engineering roots and come back to some of these key questions. So it was towards the end of my PhD and my postdoctoral training that I started to get into this field of the physics of cancer, again, introduced by my mentor to me and by these fantastic mechanical engineers that I was working with at the time. It's not my personal background, not my chemical engineers. So things like transport through blood vessels and drug uptake and kinetics, that makes a lot more sense to me than mechanics. But I started to learn, of course,

25:04on the job, which is really what we do as researchers every time there's a new research opportunity that comes around. But I just felt that there were still so many of these unanswered fundamental questions about how physics in the body impacts our cells at their most fundamental level, including our immune cells. At this point, of course, cancer immunotherapy had been under clinical trial and research for decades before I even became a graduate student. But it was during my time in

25:35Boston in those 2010s that a lot of these clinical trials started publishing success stories. So in addition to learning mechanical engineering, I also started learning immunology full force, realizing that this was going to be an important part of my approach to trying to cure incurable cancers. I started writing my faculty proposals and also these career transition awards, for example, from the NIH, with this idea of marrying mechanics or physics with the immune system under the context of

26:09cancer. And that resonated very well with Notre Dame. It did with other schools as well. I have to say that even despite it being an odd year during COVID, I had a really positive experience while I was on the faculty market. And again, I've tried to bestow some of those lessons learned and experiences to younger faculty candidates. So I think I frankly would have been happy almost anywhere. But there was something about Notre Dame's approach to engineering. I ended up in a department of aerospace and mechanical

26:40engineering, of which I hold neither degree. And they were completely willing to embrace this idea with me. They were used to talking to bioengineers. They had a cohort of half a dozen or more faculty already in this area in the context of bioengineering within the department. But because of this umbrella, it just so happened that most of those folks were very interested in biomechanics or mechanobiology. So sort of the study of mechanical forces in the body and then those consequences. So this department

27:15was already primed to start thinking that way. And then I slotted in with my very specific program on cancer and the immune system. That's fantastic. And I know finding the right colleagues and collaborators and partners in science can be instrumental in shaping your career. And we'd like to take a moment to thank our sponsor, Innovative Research, and to talk about their portfolio of ELISA kits, which offer high sensitivity, specificity, and can be used for a wide range of applications. Innovative Research ELISA kits are

27:46manufactured in their lab in Novi, Michigan, and are shipped directly to your location. They're a valuable tool for researchers and clinicians who need to detect and quantify specific biomolecules. Visit www.innov-research.com. That's www.innov-research.com to view their entire line of ELISA kits. And now returning to our conversation with Meenal. Meenal, you found a great fit there at Notre Dame, as we mentioned, and you're doing really exciting research there.

28:16So is there a project that you're working on right now that you are super excited about

Studying glioblastoma in space

28:21and you want to share with everybody today? One of the cancers that we study most often in my laboratory is called glioblastoma. It's an incurable brain tumor. It arises in adults. It's a primary tumor. So unlike some that might metastasize to the brain, this one starts in the brain and stays there. And despite crucial development over the last few decades of targeted therapies, of immunotherapy, et cetera, these have really failed to have a lasting impact,

28:52a durable impact for a large number of these patients. So like a classic engineer, we love to solve these unsolvable problems. And this felt like one to me and to my lab. So when we first established the lab, we started building up these experimental models to study these interactions between physics, cancer cells, and immune cells. So we could do that in a Petri dish. We could do that in mice. These are the two models that I trained on most often. But at this time, a few years ago,

29:23these three-dimensional models that are now being called, for example, new approach methodologies or non-animal methods, NAMs, these were really becoming highly popular in the field. And they were very attractive to my students who didn't necessarily want to jump right into an animal study, which of course, I completely understand. We started building these new three-dimensional models of glioblastoma, also of triple negative breast cancer, and of a few other cancers as well. But while we were doing this, we were noticing that these aren't quite as easy as they seem, right? One of these organoids,

30:00so these tumor-like 3D constructs, compared to its neighbor could look and behave totally different from the one next to it. And I can skip a long story by saying one of the main reasons that this happens is actually due to gravitational artifacts. So gravity in our cultures is inducing buoyancy and free convection and sedimentation. And all of these effects are actually hindering our ability to do this study. So for me, our most exciting project right now is where we are escaping gravity in order to do our

30:34cancer research more effectively. So we have now launched two experiments to the International Space Station, where we grew these three-dimensional organoids in the microgravity environment so that they're no longer hindered by these gravitational experimental artifacts. And this was not our idea to begin with. There has been biological research ongoing in space ever since we've been sending humans sent to space. But nobody had shown that the space environment could be useful for this disease,

31:08for glioblastoma, and specifically for these three-dimensional models of this disease. What we have found through our studies is that we can create a model just using the microgravity environment that much better recapitulates the advanced human disease that we as humans evolved to have here at 1G. So this is a totally new area of science for us. And there are still so many questions to be answered. Definitely. And I think one of the perks of being in this aerospace and mechanical engineering

31:39department, it sounds like, is this opportunity to send your research to space. 100%. I mean, I was inspired by my own colleagues. The year that I joined in 2021, my colleague, Professor Tangfei Luo actually sent his first experiment to the ISS, which was based on bubble dynamics in fluids that you could use, for example, for detecting pollutants or even detecting biomolecules, etc. And I just thought it was cool. I mean, who doesn't think space is cool?

32:09Everybody loves space. Yeah. Everybody loves space. And so I emailed him and I said, how did you do this? And he walked me through his process, which was not as complicated as I thought it was. And so I basically phenocopied his approach onto my own research program because I had done enough reading into biological research in space that I felt confident that this lack of gravity would really allow us to create these better models. And so I was able to convince enough people of this hypothesis that they helped us make it happen. Well, Mina, I love this story. And this sounds like a really exciting project. And I know

32:44in science, though, there are challenges, there are struggles, there are failures. And I think so often those stories don't see the light of day, but I think they're really important to share. So do you have an example of something you struggled with or maybe a major failure that you went through that you could tell me and our listeners about? From my own personal career, I think the greatest struggle was those first couple years of graduate school that I had, where I was really questioning my identity as a researcher and my ability in this space. But from a more practical and more current example, I can actually tell you about how a failure

33:18in these space experiments led us to a really important discovery. We launched our first experiment with these miniature 3D tumors to the space station in 2024. And we were invited onto this launch. It was the SpaceX 30th commercial resupply mission to the ISS. And we were invited by our implementation partner company called Space Tango to participate. So they basically built a portable cell culture incubator that they call a cube lab. They can use it in modular function for basically any type of

33:53experiment. But we were using it to keep ourselves alive. We had this tiny little volumetric space that we could occupy on this in-space experiment. And we had to be really deliberate in the way that we designed our experiments because there was only so much we could send. So based on prior knowledge, there was rich literature saying you don't need, for example, any type of supportive scaffolding in space to grow 3D structures because without gravity pulling you down, they're going to grow phenomenally

34:23in three directions, whether you're growing a tumor for study or if you're growing heart or brain tissue for regenerative medicine, etc. We decided to send these up without scaffolding, except for a handful. And I convinced my students, I said, please, I know we're really limited in this volumetric space, but can we just send a few of these up in a hydrogel, in a gel that mechanically looks like the brain? Because again, I'd been thinking about these physical properties and this crosstalk between physics and biology within the body. So let's

34:57just send a few up that maybe feel like they're in the brain, which is where this tumor arises. We sent that experiment up. Of course, we can't really do anything to the experiment while it's there. But then the experiment is returned to us. So when you've seen those videos of splashdown of a capsule with the parachutes in the ocean, it's all very dramatic. That's exactly what happened for us. That was carrying our research along with the research of dozens or hundreds of other scientists and engineers. So we collected these organoids, we brought

35:29them back to the lab, we were getting ready to look at them and start to analyze them. What we had done is we grew an analog of exactly the same experiment here on Earth at 1G. So this is what's called your ground control. And it's what you compare all of your space-based research to. And when we opened up these space experiments, we found that almost all of them were dead. Very few of them had survived the experiments and the long duration that they were there in space. And this was because of the

36:00experimental constraints that we already knew about. We wouldn't be able to really feed them while they were there. With this particular hardware, of course, there are options to do so otherwise. But this was the constraint of this particular experiment. They were there for over a month, 40 days on the station. We didn't know how, let's say, the large G-forces during launch or return could impact them as well. So we kept looking at these little experimental containers, seeing one dead organoid after another, starting to feel really dejected. And then all of a sudden we get to

36:32the ones that were in the hydrogel, in the scaffolding, and those came back alive. And for us, this was just a confirmation that, yes, the mechanics matter. Even if physically you don't need scaffolding to grow a three-dimensional cell structure in space, biologically, if you're trying to recapitulate a disease like we were, it turned out that you did. And I'm so grateful that my students let me bully them into including those handful of precious samples because in our subsequent

37:05flight, where we flew up organoids that had been created directly from glioblastoma patients, we flew them all in those hydrogels, and they came back 80% successful on the next flight. So that was one of those classic scientific stories of where a failure leads you to a discovery. And now we're trying to understand better why, if we're trying to create a model of this disease, why does it rely so heavily on mechanics that make those organoids feel like they're in the human body?

37:36Well, this is absolutely fascinating. And I'm glad to hear that the story had a happy ending. We love celebrating these successes in science and these unexpected discoveries that you make along the way. Absolutely. So do you have another success story that you'd like to share with us, whether it was one of these big wins or even just a small but particularly meaningful one lately? All of these moments feel like wins. When a student walks into your office with a successful experiment and new or unique data, that can feel like a win. When you see your research blasting off

38:09to space literally on a rocket, that obviously feels like a win. At this moment, while you and I are speaking, literally while we're recording, I have two members of my laboratory who are sitting on a parabolic flight in Switzerland. These are those so-called vomit comets that they put astronauts onto to train them for zero G. So these airplanes fly in a parabola, a series of parabolas. And as they come down, it's almost like a roller coaster. As they come down, you get a few seconds of weightlessness.

38:41So my students are sitting up there right now carrying some of these 3D organoids, these tumor organoids so that we can compare these results to what we see in space and on ground. So this certainly feels like a win. I don't know how my students are feeling, but it feels like a win for me. And then, of course, any increment or recognition for my students feels like a personal win to me. The student who took the chance on our very first launch to the space station and took it upon herself

39:12to design that experiment. She was my very first PhD student and graduate from the lab. She just graduated a few months ago. And that felt like such a win to see that not only had she developed this beautiful dissertation of work marrying physics and cancer and the immune system, she'd even been able to extend it into this context of variable gravity and how that can impact our research as well. So, I mean, that felt like a feather in her cap that I couldn't have ever predicted would happen.

39:43Well, congratulations, Minel, to you and your lab members on all of these successes. And of course, I appreciate the dedication of your students in undergoing this parabolic flight. It sounds like an ordeal.

39:56They are much braver than I am. Well, I love that. And I think in addition to being able to work on these just tremendously cool projects, you get to go to really cool places as a scientist and do really cool things. So we love talking about the travel opportunities and some of these things that people may not realize are part of careers in science. So do you have a favorite place, Minel, that your research

International research collaborations

40:16has taken you? For my students, it might be the Kennedy Space Center in Florida, where they get to watch these rockets launch, which, of course, it's hard to disagree with that. But I have a more personal connection that's been built directly through being here at Notre Dame, which is the research and education collaborations and bridges that we have established with Ireland. So as you can imagine, there's a deep connection and mutual love between Notre Dame and Ireland. And an idea of a conference

40:51or something like that that comes to mind recently is we established a new collaborative with the University of Galway called the Bischock Cancer Collaborative. And Bischock in Irish means to heal. So there's now this consortium of cancer researchers here at Notre Dame who are part of our Harper Cancer Research Initiative and a group at the University of Galway, many of whom take the same sort of mechanics or physics-based approach to cancer. So it's not just me and it's not just Notre Dame.

41:22This is a really burgeoning field at this moment. What was really beautiful is we came together last May for a two or three day meeting where we had a chance to really just sit in a room together and talk about these common approaches that we're taking literally across an ocean. We're all trying to solve the same problem and we're trying to take complementary approaches to do so. And I've enjoyed every time I've had an excuse to travel to Ireland for either educational reasons. Another trip that I enjoy a lot is a graduate writing retreat that we'll take students on for a week each year, but also for these research

41:58experiences as well. And that's been really fulfilling for me. This sounds amazing. So what are some of your favorite things to do or see while you're in Ireland? Of course, you have to go to all the tourist attractions. When I was there most recently this past June, I finally, after many trips, saw the Cliffs of Moor, which was just amazing. I enjoy every part of the country I've been to. For me, Dublin reminds me quite a bit of Boston, having spent so much time in Boston, of course, during my training and my life. But then we at

42:31Notre Dame were really fortunate to have this beautiful facility in the west of Ireland, deep in the Connemara at what is essentially a castle. It's also a convent. And we've built out essentially a dorm where we stay there and we host research and education programming. It's called Kyle Moore Abbey. And my experiences there have been some of the highlight of my career thus far. Oh, how fun. What a cool opportunity. And it's great to hear about these international collaborations. And I think science does give you these opportunities to build bridges and to work

43:04with people all over the world. And I think it's a really good way to dispel stereotypes that I think people still have about scientists and life as a scientist, because the way that we're portrayed in the media is typically not true to life. So do you have stories, I guess, that go against these stereotypes, whether it's quirky lab traditions or just funny or fun things that you've done with your lab members over the years? I have to say my lab members are much more fun and funny than I am. Yes. I think you're great. Oh, thank you. I'm sure they have many internal jokes, but it's always funny when you see like a

43:39label in lab, they might name something. I saw recently somebody had named one of our cryotanks, Mr. Frosty. Another funny anecdote that I have almost every single year is when I came here to Notre Dame, you know, they're very good. I think in part owing to their football and their athletics program, Notre Dame is really excellent about bringing research into that brand of the whole university. I personally have benefited from that. So I've had what we call these football commercials

44:10that air during a game and they'll air on TV as well, highlighting research stories here at Notre Dame. Oh, cool. But one thing that Notre Dame does really well, of course, is they put together these excellent brand assets. And so when I first came here, I said, can you give me a PowerPoint template that I can use to structure my talks now that I'm here at Notre Dame and I want to present from Notre Dame. So our marketing department gave me this template for PowerPoint that was full of these stock photos of people really poorly miming science, pretending to pipette or looking in a microscope that wasn't turned

44:46on. So what's so funny is twice a year, once per semester, we have what we call our undergraduate research symposium in the lab. So in addition to all the fantastic staff and postdoctoral fellows and graduate students, at this point, I think I have 25 undergraduate researchers, hopefully having the same experience I had when I was an undergraduate researcher. And I want them to feel like they are as important in contributing to the mission and the research of the lab as any other senior

45:16member. So twice a year, we'll have a symposium that's just for them, just for their presentation. But without fail, these students always present with these silly stock photos every time. And so it's just become a running joke for us. I love that. They need to like reenact their own stock photos so they can contribute to the library. They have started to Photoshop themselves in, which is equally amusing. I love that. Well, I think this really showcases that sense of humor in science. And I think that's something that people don't necessarily associate with scientists, but we're trying to,

45:49like I said, break those stereotypes and get people to think more broadly about who science is for and who fits in science as well. And I'm sure you feel the same, Marie, but I think science is for everyone. Oh, absolutely. 100%. And even if you don't pursue it as a career, I think you should still be engaged and sort of think scientifically about the world. Exactly. Even just the areas that we've touched on today, right? Human health or human disease or space exploration. These resonate with everyone.

46:19Absolutely. And I know your lab is answering some big questions that are relevant for human health for most of the people in the world out there. So oftentimes you're faced with barriers. We talked about some of the challenges and struggles today, but oftentimes it's funding, technology, feasibility, just these things standing in your way. So if you had all of the resources you

Dream questions and closing advice

46:37could dream up and there were no barriers, Meenal, what is your dream research question that you would want to answer? I think I would answer the same question I'm trying to answer now, which is how do we use engineering approaches to cure incurable cancers? But I think the difference would be I would use that unlimited funding or resource to enable us to do that technologically. So for me, if I had unlimited resources, I would build a permanent lab in space for me, for my lab, for Notre Dame,

47:08for anyone who wants to do this type of research. And the good news is, is actually the space economy is working that way anyway. As the ISS retires in the next few years here, it will be replaced by a number of commercial space stations. And so we will certainly engage in that way. But if I had unlimited funds, I would launch my own station. Well, I love this idea of like a dream space lab. So I appreciate you thinking big with us on the show here and you've shared so much today. We would love to end by talking about advice. So Meenal,

47:41is there one piece of advice that somebody gave you that really helped you that you can share with all of our listeners today? It's a little bit of a privilege saying, but I think one that's really resonated with me is to not be afraid to fail. And I know that that means that you likely need some sort of a safety net or second plan should that failure happen. But if you're fortunate enough to be in a position like that, absolutely take risks. Don't be afraid to fail. Take lessons from my life and from so many

48:12scientists like me that life is not a straight path. It's circuitous. Things happen in a journey and really just to believe in yourself and take that leap of faith. Well, I love that message. Thank you for sharing it with me and our listeners. Is there any other last piece of advice or perhaps a last note of inspiration that you want to leave everybody with at the end of our conversation today, Meenal? I just want to say dream big and be open to new ideas. Even for our lab and my own personal research, I trained as a chemical engineer for many years, for well over a decade. And then all of a sudden,

48:47I came into mechanical engineering, into physics, and applying that to the same questions I'd been trying to answer. That felt like a reinvention point. And it was something that I had to be open to at the time. And now we've expanded this research into space literally just in the last three years. I wasn't thinking about any of this when I went on the market in 2020 and started my job in 2021. And look at how fast things progressed just because we took that chance. So dream big and take big leaps.

49:19Well, wonderful note to end on. Meenal, if our listeners want to learn more about you or the work that you do, what is the best way for them to get more information or get in touch? I would love to hear from anyone. You can find me through Notre Dame's websites. Our lab has a website, timelab.nd.edu. And you can find my email. You can find our publications. Please reach out. Outstanding. Well, thank you for sharing those resources. And thank you so much for taking the time to speak with all of us today. It was such a pleasure, Marie. Thank you so much.

49:50Well, it was a delight to have you here with us. Listeners, always great to have you as well. We hope you'll join us again for another episode of People Behind the Science.