01;00;08;21 – 01;00;35;24
VO Victoria
Welcome to Beyond Lab Walls, a podcast from the Salk Institute. Join hosts Isabella Davis and Nicole Mlynaryk on a journey behind the scenes of the renowned research institute in San Diego, California. We’re taking you inside the lab to hear the latest discoveries in cutting edge neuroscience, plant biology, cancer, aging, and more. Explore the fascinating world of science while listening to the stories of the brilliant minds behind it.

01;00;35;27 – 01;00;49;12
VO Victoria
Here at Salk, we’re unlocking the secrets of life itself and sharing them beyond lab walls.

01;00;49;14 – 01;01;08;15
Isabella
Today we welcome Laura Mainz, who’s a trained cancer biologist that spends her time at the Salk Institute studying a process of programed cell death called autophagy in the context of tumor initiation. Welcome to the podcast, Laura. Let’s start at the very beginning. Where were you born and raised?

01;01;08;17 – 01;01;24;25
Laura
I was born and grew up in Germany, midwest Germany, close to the border of Belgium and Netherlands, in a very tiny village. We had just 2000 people. Also a lot of farmers around, so probably as much people as cows, I would say.

01;01;24;27 – 01;01;32;17
Isabella
Was all the farming something that got you thinking about science and animals and plants, or was that anything on your mind when you were younger?

01;01;32;20 – 01;01;48;12
Laura
Not really. I mean, I was always curious about the human body, especially when I started. Plant biology was really not my cup of tea. It was really too boring for me. It was always the human body that I was interested in.

01;01;48;17 – 01;01;56;03
Isabella
So then at what point did you realize, going through school that you might want to pursue science more seriously?

01;01;56;06 – 01;02;22;28
Laura
In the beginning, I thought studying medicine would be my path to go. And then when I was in high school, I did two internships. My school required one, but I did two. One in a hospital and then another one in a pharmaceutical company close by. And I kind of realized that working in a lab is more interesting to me.

01;02;22;28 – 01;02;43;27
Laura
And that was also the first time that I ever used a pipette. And then I thought, okay, I really would like to study biology. And I applied for a bunch of different universities. And also I really did enjoy biology in school. Also math, which many people hate.

01;02;43;29 – 01;02;52;12
Isabella
So you got to college, you knew what you wanted to do and it was kind of biology. When did it start becoming more cancer biology?

01;02;52;15 – 01;03;30;09
Laura
So when I studied biology, of course, you get the broad introduction and everything. And it pointed out that I was interested in cancer relatively early on. I did focus on molecular biology, human genetics. So these were my two majors in my undergraduate. And then why I got into cancer biology especially, and every time into more depth with something I would say I probably realized maybe retro perspective why I did this.

01;03;30;11 – 01;03;59;21
Laura
So my, my father was diagnosed with multiple myeloma when I was in high school. And of course, that was a huge hit for our family. Now, I would say I did this or I did study, especially cancer biology, because that’s the way I cope with the whole message we got in our family, because I felt very helpless in that moment when we got that diagnosis, and I didn’t really know what should I do.

01;03;59;24 – 01;04;24;14
Laura
And I also didn’t really had all the knowledge. I mean, when the doctor told us he has multiple myeloma, I said, what? I never, ever have heard about this. And I did the one mistake that you basically actually never should do. I looked it up online. I found Wikipedia and it said five year of the survival rate, which was not the case anymore.

01;04;24;14 – 01;04;43;23
Laura
It was really not up to date statement on Wikipedia and I yeah, I just felt I—knowledge helps me in the future to cope with the situation, whatever comes next.

01;04;43;25 – 01;04;58;09
Laura
He thought nine years. That’s that’s definitely more than what Wikipedia told us. But he he was a fighter.

01;04;58;11 – 01;05;10;01
Isabella
And at that point, did you consider going into like oncology and were you still thinking about medicine at all, or were you deciding maybe research and development of drugs?

01;05;10;01 – 01;05;46;12
Laura
For me, going the academic career was something I never really question until I would say last year. I actually started to volunteer for a nonprofit organization here in San Diego. It’s called Leukemia Lymphoma Society, and I do patient outreach for them. And also last year I had the chance to do advocacy for them, especially for pediatric cancer. And that’s something I never actually imagined to enjoy doing patient outreach, working with patients, doing advocacy.

01;05;46;13 – 01;06;20;11
Laura
So so yeah, I’m at the point in my life where I need to figure out it’s academia or working in an academic field is still what I would like to do in the future. Or maybe pivot a little bit more into working more with patients. I can imagine working, for example, in clinical trials would be something that really interests me, but I do really enjoy what I’m doing here right now that I just these are just thoughts I have for my next step, my next goal.

01;06;20;13 – 01;06;24;08
Isabella
So how did you end up in San Diego?

01;06;24;11 – 01;06;50;23
Laura
I found out about Salk already when I was in my bachelor, in my undergraduate, and I did my bachelor’s thesis in a lab that had a collaboration with a pharmaceutical company here in San Diego and the PI (primary investigator) in that lab also offered me, if I would like to do part of my thesis here in San Diego at that company. That was, of course, a huge offer for me as an undergraduate student.

01;06;50;26 – 01;07;17;20
Laura
So I looked into the company and also into the city and what else was around, and found out about Salk. I was really fascinated about that institute, and it just gave me a very positive vibe about how research is done and how good our collaborations are done here. But then I decided not to take the opportunity to go to San Diego because that company also had financial issues.

01;07;17;22 – 01;07;48;09
Laura
Then a year before I finished my PhD, I again looked into that institute and searched throughout the different labs and then decided to apply for Jan Karlseder’s lab. And then I got here in 2019 for conference, because I just didn’t want to do an interview via Zoom. I think in person is always better, and it was perfect timing because he was looking for someone who already has expertise in autophagy.

01;07;48;09 – 01;07;50;16
Laura
What I worked on in my PhD.

01;07;50;19 – 01;07;53;06
Isabella
Can you explain what autophagy is?

01;07;53;09 – 01;08;35;13
Laura
Yeah. So to break it down, autophagy is a recycling pathway in our body. Meaning for example, our old organelles, old proteins or damaged proteins in our body, which is, let’s say, floating around in our body and would probably harm the body because it’s not functional anymore, needs to be caught and broken down into individual compartments so that once we have these individual compartments, we can again take them and use them to build new organelles in our body, new proteins that again, are functional and healthy and especially young.

01;08;35;16 – 01;09;07;14
Laura
We need that recycling process to maintain our protein homeostasis in our body. And actually we can also increase autophagy. I think many people who are interested in fitness have probably already heard it that once you starve your body, you activate autophagy because the body thinks, okay, I need to recycling things in my body to increase my energy, to break down things in my body that that’s not functional, that’s old, that’s broken.

01;09;07;16 – 01;09;26;24
Laura
Intermittent fasting, it’s exactly that. So basically, you starve your body for a specific amount of time and that induces autophagy and helps to recycle things in your body that usually has detrimental effects if it’s just accumulating in our body.

01;09;26;26 – 01;09;37;22
Isabella
Oh, interesting. That’s great you had the exact specialty Jan was looking for at Salk. Was deciding to leave Germany difficult, or were you expecting to do that after the PhD?

01;09;37;24 – 01;09;59;01
Laura
I always had the idea to go abroad at some point in my life, and when I finished my undergraduate, I had the feeling, I’m not ready to do this, I would like to stay a little bit longer in Germany. But then five years after, it was exact opposite. So I felt okay, now it’s the right time. I’m ready.

01;09;59;01 – 01;10;06;14
Laura
I’d like to do this. I’m just in the right spot to grow into that new challenge.

01;10;06;17 – 01;10;12;21
Isabella
Do you visit home much? Or do you find yourself traveling more in and around North America?

01;10;12;24 – 01;10;41;14
Laura
Of course, you always would like to travel more than you in the end do. I have visited a couple of places here, especially in California. Also before actually coming to San Diego, I visited New York with my family and then my best friend, she lived in Pensacola, Florida for almost two years, so I was there already. And going home probably once per year, I would say, because it’s it’s a long flight.

01;10;41;17 – 01;11;08;03
Laura
And last year I was very happy because my family came here and visiting me for the very first time. And also my little nephew, he is two and a half years, and he also got the chance to see me here, and I could spend a lot of time with him. That was that was amazing for me.

01;11;08;05 – 01;11;10;19
Isabella
Now that you’re at Salk, what’s your research look like?

01;11;10;23 – 01;11;47;04
Laura
So in the lab I’m working in right now, we’re general interested in telomeres. These are the protective DNA caps at the very end of our chromosomes. And we know already, through multiple years of studying and based on other labs work, that the genome has become shorter during aging. And we also know that telomere shortening induces a cascade of different signals, also including two main barriers known to prevent that a healthy cell becomes a cancerous cell.

01;11;47;07 – 01;12;33;12
Laura
And my project is focusing more on the second later on in life barrier. That’s called replicative crisis, and it’s characterized by an inflammation but also widespread cell death. And by that, the body basically prevents that, aged cells or unstable cells become a cancer cells. So the body just gets rid of them before something worse can actually happen. And then in my project, I established a mouse model where I’d like to understand if this crisis specific cell death or if defects in this crisis specific cell that leads to more tumor initiation.

01;12;33;14 – 01;12;40;05
Isabella
This crisis specific cell death that Laura’s talking about, that’s autophagy.

01;12;40;08 – 01;13;16;24
Laura
This might be the last barrier before cell actually becomes a cancer cell. That’s the idea of my project. And I’ve worked on this specific cell, this pathway, which is a known pathway in our body that also happens on a normal, regular basis. It’s basically a pathway that regulates protein homeostasis. And I’ve worked on that pathway already in my, PhD because it’s a known tumor that is deregulated in general in cancer cells, not only in early tumor cells.

01;13;16;26 – 01;13;25;17
Isabella
You mentioned you’re creating a mouse model. Are you mostly working with mouse models of pancreatic cancer or what type of cancer? Or is it a couple different types?

01;13;25;20 – 01;13;54;07
Laura
So in my project I have two different approaches. So my mouse model is focusing on the whole body. Meaning I have mice that have shorter telomeres over time, and I combined it with autophagy impairment. And then I see which tumors arises, or do I get one specific kind of tumor type more than others? And where do the tumors arrive?

01;13;54;08 – 01;14;29;02
Laura
Is it maybe one specific organ that is affected more than others? And then on top of this, I have another mouse model that focuses more on the liver. What has to be known about the liver specifically is that liver cells don’t divide very often, while every other cell in our body divide relatively often. So I try to compare if what I do see, maybe in my whole body mouse model is the same in the liver, where I have cells that don’t divide very often.

01;14;29;04 – 01;14;41;22
Isabella
Oh, interesting. So you’re looking at this whole body model and seeing how shortened telomeres and autophagy can affect cancer development, and if there’s a particular area of the body where cancer is more likely to develop?

01;14;41;24 – 01;15;08;16
Laura
I don’t know yet. I did develop that, these models and I’m at that point where I have them, it took me three years to get there. So that’s a long term, experiment, let’s say. I’m in that point of my project where I monitor those animals and I will analyze or take the organs whenever I do have a mouse that’s sick or it’s not going well anymore.

01;15;08;16 – 01;15;18;04
Laura
And then I take different parts of the body and see if a tumor arises in specific compartments of that body. But I’m not there yet.

01;15;18;06 – 01;15;23;00
Isabella
Yeah.

01;15;23;02 – 01;15;59;11
VO Victoria
If you’re enjoying this episode of Beyond Lab Walls, be sure to check out our other channels at Salt.edu. There you can join our new exclusive media channel, Salk Streaming, where you’ll find interviews with our scientists, videos on our recent studies, and public lectures by our world-renowned professors. You can also explore our award winning magazine, Inside Salk, and join our monthly newsletter to stay up to date on the world within these walls.

01;15;59;14 – 01;16;05;13
Isabella
Does your lab and your work have any overlap with Christie Towers’ lab? Since they’re also looking at autophagy?

01;16;05;15 – 01;16;43;01
Laura
I would say I’m the first in our lab who really works into autophagy itself. So a colleague of mine who discovered the fact that cells in crisis are in these last barrier dies through autophagy, that that’s these crisis specific cell deaths. So he discovered that and then I continued working in that part of of the project. And since we are more interested in tumor initiation, and Christie Towers’ lab is more interested in how does a tumor cell resist to autophagy inhibition.

01;16;43;01 – 01;17;16;01
Laura
Because autophagy, again, is a pathway that’s deregulated and very often upregulated in cancer cells. So the original idea was what if we target autophagy in these cells. And cancer cells use autophagy as a recycling pathway to get new energy. And the idea is if we target that pathway, they can’t generate energy through autophagy anymore and they die. That was in general a good concept.

01;17;16;01 – 01;17;50;24
Laura
But of course there are always cells. They are resistant to that or they activate different pathways to compensate the loss of autophagy. So I think our two labs of my project and Christie Towers’ lab is interested in two different parts. While we are working more and how is on top pretty important that cancer arises, she’s more interested in how can we use autophagy as a therapy and especially can we target it with a second hit once those that has been targeted with autophagy inhibition.

01;17;50;27 – 01;17;58;26
Isabella
How much overlap are you finding between your research and your findings and research and findings on aging?

01;17;58;29 – 01;18;25;16
Laura
I mean, aging is a cancer related disease, so it one comes with the other, I would say. Before I came to Salk, I was not really interested in death in any age-related disease. I was always understanding cancer and trying to understand what has to go wrong, because there are so many processes in our body that just go smooth.

01;18;25;16 – 01;18;41;11
Laura
There’s nothing happening, or at least the bodies always able to cope any, let’s say, mistakes. But what has to go wrong that a healthy cell actually becomes a cancer cell? That’s super interesting to me.

01;18;41;14 – 01;18;46;16
Isabella
And do you have any questions that you’re excited to ask in the future?

01;18;46;18 – 01;19;13;08
Laura
I mean, asking questions… It’s our daily business. The main question is really, why is this specific process or can this specific cell death really be the last barrier? Or is there maybe something afterwards where the body implemented, maybe a third barrier that we don’t know about it, that again prevent the transformation of a healthy to our cancer cell?

01;19;13;11 – 01;19;16;29
Isabella
And is there anything else that you do other than lab work?

01;19;17;05 – 01;19;40;20
Laura
I do really enjoy having a work life balance, so I do enjoy doing my work here, but we dedicate a lot of time and hours to our job, so I think I like to have a clear cut sometimes of okay, I try to switch off my brain and just go home and try other things than science.

01;19;40;22 – 01;19;46;15
Isabella
What are some of your favorite things to to do when you’re turning off your brain at the end of the day?

01;19;46;18 – 01;20;11;27
Laura
In general, I like to be active outside of the lab, so I’m a runner. I go to the gym. Fitness in general. I do really enjoy, going for a hike with friends. In general, activities with friends I do really enjoy. I also, I’m a dancer. So I started ballet when I was seven, did a bunch of different types.

01;20;11;28 – 01;20;39;08
Laura
I did ballet, jazz, hip hop, modern. Then I got lost track a little bit, and then once I actually came here and, the pandemic was a little bit, over, I started to salsa, Cuban salsa, bachata. So I got back into it. That’s something I really do enjoy. And and yeah, since last year, the volunteering work—helping others was always part of my, my life.

01;20;39;10 – 01;20;42;10
Isabella
So can you still do all the ballet positions?

01;20;42;10 – 01;20;55;13
Laura
I can. I think that’s something you never, forget. Yeah, just the split. That’s that’s that’s a difficult thing.

01;20;55;16 – 001;21;32;05
Isabella
I was going to ask with the dancing, too—do you feel like that kind of creative hobby outlet has felt totally separate from the science in your life? Or do you feel like that kind of creativity throughout your life has inspired or helped you to ask more interesting questions? Or to, you know, think outside of the box more in the lab?

01;21;32;07 – 01;22;02;11
Laura
That’s a difficult question, and I never thought about that. I mean, I have to say, I stopped with ballet in the same year when I finished high school and started my undergrad, and I never really considered myself as a creative person. But dancing is kind of being creative, but just with your body, not with other skills. I think for me, dancing and being active, it helps me to switch my brain off actually.

01;22;02;11 – 01;22;18;14
Laura
So probably the opposite of what you just thought because again, we spend so much time in thinking about science and problems and things we like to solve, it’s it’s good we have our moments where we actually say, okay, I’m not thinking in all.

01;22;18;17 – 01;22;44;03
Isabella
I think it’s wonderful to have the work life balance. It’s very important, especially when you’re doing such hard work and you’re doing something also that is so fulfilling to you, and it feels like you’re able to target this feeling of being out of control, put it to work, and use that as fuel in the lab. What’s exciting you most about your research in the years to come now?

01;22;44;03 – 01;23;08;08
Laura
I think for me personally, nowadays we are all focused on finding a treatment for cancer and don’t get me wrong, that that’s very important, but I think we sometimes forget that we also should focus on the fact that maybe we should take care more of our body and make sure that we don’t even get in the first place.

01;23;08;08 – 01;23;34;24
Laura
And the reason why I mentioned this is that my project focuses exactly on that. So what do we need to know about cancer tumors initiation that helps us to prevent cancer in the first place? Because just hearing the words “you have cancer,” and that was not even to me, that was my father, has had a huge impact on you and your life.

01;23;34;26 – 01;23;54;12
Laura
And I mean, in my family, it was a cancer that that is treatable, but it’s not curable. and even if it’s a cancer that’s curable, it still affects you a lot. And I hope that in the future, less people actually hear these words.

01;23;54;14 – 01;24;00;09
Isabella
Well, thank you so much for coming and talking to me and sharing your story and your science.

01;24;00;11 – 01;24;09;22
Laura
Thank you. Thanks for having me.

01;24;09;24 – 01;24;40;08
VO Victoria
Beyond Lab Walls is a production of the Salk Office of Communications. To hear the latest science stories coming out of Salk, subscribe to our podcast, and visit Salk.edu to join our new exclusive media channel, Salk Streaming. There, you’ll find interviews with our scientists, videos on our recent studies, and public lectures by our world renowned professors. You can also explore our award winning magazine, Inside Salk, and join our monthly newsletter to stay up to date on the world within these walls.