Introduction:

Welcome to the Salk Institute’s 治愈的起点 podcast, where scientists talk about breakthrough discoveries with your hosts, Allie Akmal and Brittany Fair.

Brittany Fair:

So I’m here today with Dr. Nikki Lytle. She is a postdoctoral researcher in the lab of Professor Jeffrey Wall, where she studies the protein interaction involved in cancer. Welcome to Where Cures Begin.

Nikki Lytle:

Thanks for having me, Brittany.

Brittany Fair:

Absolutely. And just to start out, I was wondering, are you originally from San Diego ?

Nikki Lytle:

I’m not. I’m from Central Oregon. I’m actually from a very tiny farming community called Culver. And growing up, there was about 800 people in Culver. The biggest city closest to Culver is Bend, Oregon, which more people have heard of. Very small town and classic farming community that you can imagine a lot of farming families that have been there for decades and know each other very well.

Brittany Fair:

And were you raised on a farm as well? [animal noises]

Nikki Lytle:

I was. I grew up—my dad is a farmer. My grandpa’s a farmer. So our farm wasn’t a very big farm, but it certainly kept us busy. We had cows and sheep when I was younger, but then later in life, it switched fully to commercial agriculture, like vegetables and whatnot. But we always had pigs and it was a fun little farm. We actually grew a lot of mint, which was really nice. After heavy rain, it always smelled amazing.

Brittany Fair:

Is it like mint that you would use and sell to a grocery store?

Nikki Lytle:

It was a spearmint. You would extract the mint oil out of the spearmint and use that for gum.

Brittany Fair:

Oh, that’s so interesting [rooster crowing]. And so how did you first become interested in science and possibly studying science?

Nikki Lytle:

That’s a really hard question for me to answer because I just always remember liking science. I don’t think that there was a moment in my life where I was just like, “Wow, science is great.” For some reason it was just always there, that I can remember. And in fact, I want to say the first profession that I remember saying that I wanted to do when I was a child is—I told everybody I wanted to be a genetic counselor and I have no idea where that came from. So I’m not even sure I knew what a genetic counselor was, but I just had decided that’s what I was going to do.

Brittany Fair:

That’s great. And then did you study science in college?

Nikki Lytle:

I did. Yes. I definitely focused on science starting in probably high school, took as many as I could and then continued in college, but actually in college I got a degree in biology with a minor in chemistry, but I also got a degree in religious studies with a minor in classical studies.

Brittany Fair:

Why did you also have interests in religion and philosophy?

Nikki Lytle:

I would say I’ve always been interested in the way that people form the world around them, both physically and mentally. So, I find religions to be extremely interesting. It really can alter the way a society functions together. And so I see that religion can impact the world around us, everything from the way we think to the way we interact with other humans.

Brittany Fair:

And when did you first kind of decide that you wanted to pursue research? Did you work in a lab at all in college?

Nikki Lytle:

I did. I had decided by high school that I really wanted to be an experimental research biologist. And so by college [time], I didn’t know what I wanted to do yet. I was very interested in many different sciences. So my first position was actually at an agricultural research center in Central Oregon. And when I worked there, I was helping trying to develop no-burn Kentucky bluegrass variety, so that people who grow Kentucky bluegrass seed for, let’s say golf courses—but you have to burn in between the seasons to continue to maintain high yield. And that can be very detrimental. So there were a lot of efforts trying to develop what’s called no-burn Kentucky bluegrass at the time. And I also worked on eradicating a fungus that’s called white rot, that contaminates garlic fields. And that can also be very detrimental.

Brittany Fair:

Interesting. So when did you make the transition over to studying more mammalian and human elements, such as cancer?

Nikki Lytle:

Well, from that agricultural research experience, I realized that I did want to move into a more human disease-based research program. So I moved into a research field where we were trying to study axonal transport. And that is the movement of cargo from one end of an axon to the other end of an axon. And because axons can be so long, that process is very critical.

Brittany Fair:

So then did you go to graduate school to pursue studying this topic?

Nikki Lytle:

No. After undergrad, I actually spent two years in a lab in Portland and there we were studying epilepsy, traumatic brain injury and schizophrenia. And so this was much closer to translational biology. And that’s really when I fell in love with this idea of working on translational research. I actually told myself I would never work on cancer [laughter]. And then somehow I ended up working on cancer, so.

Brittany Fair:

Why would you tell yourself that you would never work on cancer?

Nikki Lytle:

I was told that it’s an overly saturated, competitive field, that there’s too much research, not enough money kind of thing.

Brittany Fair:

So then you started studying cancer. And what type of cancer were you studying?

Nikki Lytle:

In graduate school, I worked on pancreatic cancer. And I think that’s one big reason that actually drew me to cancer research because I found it so fascinating that we’ve made so much progress in many different cancer subtypes, and yet none of the same therapeutic approaches are at all successful in pancreatic cancer. It seems to be completely nonresponsive to many of the other therapies that have worked in other cancer subtypes.

Brittany Fair:

And you’re still studying cancer today at the Salk Institute. Are you still studying pancreatic cancer?

Nikki Lytle:

I am. I’m working on actually both pancreatic cancer and breast cancer with a specific focus on basal-like or triple-negative breast cancers.

Brittany Fair:

I’ve heard you self-describe yourself as naively optimistic about finding a cure for cancer. What makes you put it that way?

Nikki Lytle:

I should start by saying I’m optimistic because I feel that the technologies and insights and progress we’ve made in recent years is extremely exciting. I think that we now have a knowledge base of the biology that’s happening in cancers that was really lacking, even 10 years ago. So that’s the optimism in me. Now, why I describe it as naively optimistic is, my guess is that 10 years ago people felt that way as well. Because probably during the genetic revolution, there was probably a lot of optimism at that time that now we have enough understanding to defeat cancer. Turns out, that’s not the case. We actually don’t know what’s going on just from the genetic drivers alone. And there’s a lot of cells that contribute to cancer that are actually not tumor cells themselves. Now there’s been a lot more research trying to understand all of the intricacies that go into a tumor.

Brittany Fair:

I see. Do you think we’ve made progress towards figuring that out?

Nikki Lytle:

I do, and some of the best progress that’s been made has actually happened at the Salk with very talented researchers and tumor immunity. So essentially the white blood cells that are in the tumor and contributing to the tumor—and we also have other scientists studying fibroblasts that play very critical roles in tumor initiation and maintenance. And so, as we start to piece this puzzle together, I think we’re getting closer to developing intelligently-designed therapeutic approaches for treating cancer.

Brittany Fair:

Wow, that’s really exciting. And this year was a huge year for you because you won two major awards. The first [award] was being named Hopes Fund for Cancer Research 2020 Postdoctoral Fellow. So what is this fellowship and what will it enable you to do?

Nikki Lytle:

Yes, I’m extremely excited and grateful to have been named one of the fellows, particularly because this is a very small fellowship, meaning that they only fund about two to three fellows a year. They really spend a lot of effort maintaining a network of scientists who have been Hope Funds’ fellows in the past, and this network meets every year and there’s actually a lot of collaboration between these past and present Hope Funds’ fellows. So in a way, I’m excited at the thought of being able to work with some of these top-tier scientists in the world.

Brittany Fair:

And did they fund a specific project that you’ll be working on?

Nikki Lytle:

Yes, it will be funding my studies that are involved in pancreatic cancer metastasis. So metastasis is the process of a tumor leaving an original place, in this case the pancreas, and then spreading to other organs throughout the body. Pancreas frequently will metastasize to the liver, and actually patients who have liver metastasis have poorer prognosis than patients that have metastasis in other organs. So this is a big problem in our field, trying to understand why it goes to the liver and what happens at the liver that will allow this disease to continue growing and spreading in the patient. So what they funded was a project looking at if liver damage itself can actually encourage or promote metastatic progression in the liver. The reason why I proposed this project was because obese patients often will have a nonalcoholic fatty liver disease, or even nonalcoholic steatohepatitis—which are both forms of liver damage. They actually have higher rates of metastasis to the liver and even poorer prognosis.

Brittany Fair:

哦，有趣。.

Nikki Lytle:

Yes. And then similarly, patients who consume higher amounts of alcohol on a regular basis and may have liver damage from the alcohol intake, they also have higher rates of metastasis to the liver and poorer prognosis.

Brittany Fair:

You’re basically seeing this link between liver damage and metastases going to the liver in these patients. And so you’re wondering why is there an actual correlation or is it potentially causal? Is liver damage enabling these metastases to go there more easily?

Nikki Lytle:

Exactly. I guess the final note that made me really interested in this relationship between liver damage and pancreatic cancer metastasis was, I started really reading about some of the literature from studying just liver damage and the liver is actually very regenerative. If you damage it, there’s potent regeneration programs that kind of kick in that allow the liver to heal itself. And actually a lot of the factors that are involved in liver regeneration are also factors that we know that drive pancreatic cancer progression.

Brittany Fair:

Interesting. And what do you hope to find?

Nikki Lytle:

We hope to find specific signals from the damaged liver that communicate to pancreatic tumor cells in the liver. And if those signals are encouraging the pancreatic tumor cell to survive and proliferate, we hope to be able to therapeutically block that signal in order to prevent metastatic progression in the liver.

Brittany Fair:

You also received this year, a $50,000 seed grant from the Sky Foundation. What project will you be pursuing with this funding?

Nikki Lytle:

For the Sky Foundation, I will be looking at how chemotherapies that are normally given to treat pancreatic cancer patients can actually cause liver damage that also alters the way in which pancreatic cancer can metastasize to the liver. A lot of the chemotherapies that we give patients are known to cause liver damage and that liver damage is known as C.A.S.H., the acronym is C.A.S.H. And we found that again, this chemotherapy associated liver damage will induce liver regeneration programs. And we’re starting to look at different chemotherapies and whether or not those different chemotherapies have more or less impact on liver metastasis. We have found that some chemotherapies will cause more liver damage than others. So our hypothesis then is that the ones that cause more damage will promote more metastasis.

Brittany Fair:

Sure. And what would that mean for a patient who is receiving chemotherapy? How would your findings possibly alter their treatment?

Nikki Lytle:

We certainly want to keep in mind that chemotherapy may be having more of an impact on disease progression than just on the intended use of killing cancer cells. And in that regard, could we come up with a therapy to give along with chemotherapy that would again, block that pro-metastatic signal from chemotherapy-induced liver damage. Maybe it would be more like a targeted therapy that would again, block a specific signal coming from the liver.

Brittany Fair:

What do you think your favorite part about being a scientist is?

Nikki Lytle:

I always say how lucky I am to be a scientist because it’s kind of crazy to think about how I can just ask a question and then go to the lab and try and answer that question, and I’m paid to do it. I love just being able to be as curious as I want to be and then trying to go find ways of addressing that curiosity.

Brittany Fair:

Sure. I have to ask, do you ever miss living on the farm?

Nikki Lytle:

No, but I really miss freshwater lakes and rivers, green mountains, camping in the woods and hiking in the woods. And so I have to escape to Oregon once in a while just to go get those mountains and freshwater lakes that I miss so much. I should say that I did bring part of the farm with me to San Diego. I had chickens in my backyard for about four years here. I know they all passed away of old age, but they were very happy chickens and it was very fun having them here.

Brittany Fair:

That’s great. Do you ever think you would add another farm animal to your backyard here?

Nikki Lytle:

I love goats. Actually that was the one animal my dad never let us have because he didn’t find a use for it, so it’s my goal in life to have a goat [laugh].

Brittany Fair:

I mean you can make goat cheese.

Nikki Lytle:

Yes, exactly. I love goat cheese. And they’re adorable.

Brittany Fair:

They can mow your lawn. I mean, there’s lots of uses [laugh].

Nikki Lytle:

Yes exactly.

Brittany Fair:

Do you have any advice for aspiring scientists?

Nikki Lytle:

That’s a tough one because so many of us have very different journeys. And I think I would say don’t stress about your timeline. I took my time and did some research in between undergrad and grad [school] and I don’t regret that at all. I’m enjoying the ride. So I’m along for the ride.

Brittany Fair:

If you were no longer a scientist—you were not allowed to be a scientist, what career would you have?

Nikki Lytle:

That’s a tough question, given how much I love science, but I would say first and foremost, I’d probably run a dog rescue. Then that would just be a nice excuse to have like 50 dogs.

Brittany Fair:

And what do you think the future holds for the field of cancer research?

Nikki Lytle:

I hope that it’s moving towards more intelligently-designed therapeutic interventions that are specific for cancer dependent signals. I think the breast cancer field has benefited enormously from hormone-based therapies. Granted those hormone-based therapies aren’t effective for all types of breast cancer, but if we could move that similar model and similar approach to pancreatic cancer and beyond, we would be in a much better place.

Brittany Fair:

That’s great. Well, thank you so much for joining us here on the podcast today. It was a pleasure speaking with you and learning about all of your different projects going on at Salk.

Nikki Lytle:

I really enjoyed our conversation. Thanks so much for having me.

Ending:

Join us next time for more cutting-edge Salk science. At Salk, world-renowned scientists work together to explore the big, bold ideas, from cancer to Alzheimer’s, aging to climate change. Where Cures Begin is a production of the Salk Institutes Office of Communications. To learn more about the research discussed today, visit salk.edu/podcast.