Research Matters

Dr. Glenn E. Simmons Jr. on how fats and inflammation can fuel cancer - Research Matters S2E3

• Cornell University • Season 2 • Episode 3

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In this episode of Research Matters, Dr. Glenn E. Simmons Jr., a Cornell biomedical scientist and assistant professor in the College of Veterinary Medicine, takes us inside his lab to reveal how fats and inflammation can fuel cancer – and why some communities face worse outcomes than others. Plus, he offers practical health tips, a peek at what’s next for his team, and a book recommendation to keep curious minds busy. Watch here.

Glenn Simmons, Jr.:

As the pandemic became a reality, most of the laboratories, most of the institutions shut down. I had this almost eureka moment where I thought we could probably figure out what's happening just based off the life cycle of this particular pathogen because we know that- the wastewater. In the wastewater because we knew it- I know, I mean it's gross, but so cool.

Laura Reiley:

Today we're joined by Dr. Glenn Simmons, Jr., Assistant Professor in Biomedical Sciences at Cornell's College of Veterinary Medicine. His lab investigates how fats and inflammation play a role in cancer and how science can help reduce health disparities in underserved communities. Dr. Simmons, thanks so much for coming today. Okay, so let's start with, I read you described yourself as a cancer biologist focusing on lipid metabolism and immunology. So. Lipid metabolism, can you just start there for people who are not incredibly knowledgeable about cancer, what's the connection there?

Glenn Simmons, Jr.:

So lipids is a fancy way of saying fats and all things associated with fat. So we could be talking about things like fatty acids, which are, you know, most people's experience of that is like cooking oil, right? Olive oil is one of my favorites actually. Or you could be talking about cholesterol. So that's all kind of in the same bucket. Uh. Our lab is really primarily interested in fatty acids and how they can impact how cells behave.

Laura Reiley:

Talk a little bit about kind of why there are health disparities when it comes to cancer in particular um and how have you seen this.

Glenn Simmons, Jr.:

Right. So health disparities is when any particular group of people are negatively impacted, differentially than the overall population. And so when it comes to cancer health disparities, a lot of those things can be manifested through uh socioeconomic issues. They can also be associated with geographical issues like rural versus urban, you know, residency. And so our lab is interested in the entire spectrum of health disparities. So not just those that are associated with you know, a person's origin, but also where they may actually be able to get their health care from and their ability to access that health care Uh ,can also, you know, be a very impactful, you know, uh, aspect of how they're able to overcome these diseases that we deal with today.

Laura Reiley:

You're kind of talking about cancer and epigenetics. I think the average person now has just a vague idea of what epigenetics means. Can you fill us in a little bit?

Glenn Simmons, Jr.:

So epigenetics is actually a really cool, you know, aspect of science where we're no longer just interested in things like the DNA sequence, you know, or just mutations, but we're also interested in how things that interact with the DNA itself can impact how the DNA shows up and manifests as proteins. So one of the things we talk about in our lab is how protein equals function. So you could, you know, look at things like DNA, but you don't really know what the protein may actually look like at the end of that. So it's almost like if you have a book. and you only look at the cover, but you don't really know what the book is about until you open it up and see how it plays out. And the protein is that, and epigenetics is how the DNA can actually be altered in such a way without changing the sequence and then affecting the protein and the outcome later on.

Laura Reiley:

So is this from a uh patient perspective, is this kind of saying lifestyle matters or that, or that, things that you do can impact your, your genes?

Glenn Simmons, Jr.:

Yeah, I mean, it's one of those things where we can say that everything matters. So what you do matters what you eat, where you live. Uh, and those things can either have a temporary effect. So like exercise can, you know, if you exercise a lot as a younger person, it's like, oh yeah, like I'm super healthy. But if you don't exercise for a while, well, that exercise you used to do can have some benefit, but you got to keep it going. And then there are things that can last for lifetime. So like the types of things you may inherit from a parent.

Laura Reiley:

Mm-hmm. So going back to the health disparities, why do you think they persist and is part of the problem that we haven't historically studied underrepresented communities in some way?

Glenn Simmons, Jr.:

Well, there's a lot of reasons why they persist. So one reason in particular is, as I mentioned before, the idea of location. So some of the most cutting edge research that we have available nowadays are housed within these academic health centers. A lot of these academic health centers, these medical institutes that are like known worldwide.

Laura Reiley:

Talking about like Moffitt Center, the Cancer Center, or Cleveland Clinic, or you know, all the way.

Glenn Simmons, Jr.:

So they're located oftentimes in major urban centers. And so then the people that are closer to those areas have better access. But if you're further away, you have less opportunity to access those or it's a lot more difficult. So if you, for instance, had uh an appointment that was six o'clock in the morning, but you live five hours away from the place you need to go.

Laura Reiley:

Sure. It's overnight in a hotel.

Glenn Simmons, Jr.:

Exactly.

Laura Reiley:

Sure. That makes total sense. So for yourself, you've done some, some, some work in, I know you did some work in AIDS. What did you do there? And this is a while back. This is not what you're doing now, but.

Glenn Simmons, Jr.:

It's a little bit of what I still do. So I did most of my graduate training in HIV, HIV replication and biology and immunology. And then I kind of went back to cancer, which is what I did when I was an undergraduate. But I still collaborate in that space because the immune, immunometabolism space, so how the immune system works and how the immune cells actually get the energy they need to do their job. It's kind of working the same way, whether you're talking about infectious disease or you're talking about cancer. So when I was interested in that area, I was really just trying to understand the fundamentals of biology of how the body responds to these kind of invasive forces that are out there in the world, these microbes, these pathogens. And so my interest when I went into the cancer field kind of just went from outside to focusing more intrinsically to the inside. How does the immune system now fight these cells that are now kind of going rogue in our bodies and keeps them from becoming cancer? Because we're always dealing with something that could be a cancer and when we're at our healthiest — our body is able to get rid of those cells pretty readily, but it's when we get a little bit more aged It becomes more difficult for our bodies —

Laura Reiley:

You're not looking in this direction, are you?

Glenn Simmons, Jr.:

No, at all not at all not at all because we all we all have some aspects of our System that isn't necessarily gonna be tip-top shape at any given time imagine for instance when a, a mother becomes pregnant for instance her immune system changes and oftentimes it actually ramps up in some regards, but she also could become susceptible in other regards. And we all have different versions of that, you know, across the uh spectrum of life.

Laura Reiley:

So in your lab now, what are the kinds of big questions that you're asking? What would be, give us an example of an experiment from the past year or so.

Glenn Simmons, Jr.:

So one of our, like the thing that kind of gets us out of bed in the morning or in middle of the night, depending on the experiment, is the idea that when an individual has a particular lipid profile, so certain types of fatty acids that are kind of in a certain homeostasis or balance in their body, that person may respond better to the immunotherapies or the different types of treatments that are available for patients nowadays. But if the person doesn't have that available, then that person may end up more susceptible to succumbing to the disease. And so we're starting to see evidence that that actually exists in patients and in patients that we wouldn't think that would benefit are the ones that are benefiting. And so we're looking into understanding the mechanism behind it. It's kind of a controversial area because it's a little counterintuitive to what we would normally think that individuals who may have increased levels of a certain fat might be the ones that are responding better because generally in the population, we think of fat as bad and lack of fat is good. But I think there's more of a balance and it's more nuanced. And as you look at this at the molecular level, you start to see the pieces actually come together in a very, uh, almost sophisticated way to keep things healthy because all large cells are requiring different things at different times. And particularly when we're trying to battle disease, we need certain fats for our body to kind of ramp up that immune response to take care of those things that are trying to make us sick.

Laura Reiley:

I mean, I know access to immunotherapy has really ramped up significantly. It's like 56 % of cancer patients have access. But of the people who get it, only 20 % respond well to it. So is this the explanation or is this among the explanations for why? What are the other reasons that people might not respond to immunotherapy?

Glenn Simmons, Jr.:

I think it is amongst a constellation of different things. And this is just one of those that I don't think anyone has thought about. And that's why we're so excited about it, because the ability to perhaps change that is so accessible, because this might be something that falls into the realm of like nutraceuticals. Can we find a dietary way of altering the lipid composition in an individual as opposed to just coming in with, you know, the newest drug that's completely artificial?

Laura Reiley:

Interesting. I guess that speaking of the newest drug, so are GLP-1s on your radar is something to study about how they connect to, you know, immunotherapy or, or lipids? If people are in this, you know, race to lose 20 % of their body fat, how does that affect what you're thinking about?

Glenn Simmons, Jr.:

Ooh, I almost don't wanna talk about that because I don't wanna say anything that's too inflammatory, but we are concerned about it because again, there's the balance. And so one of the things that we know and we actually came across this idea back when I was studying HIV replication in patients, oftentimes the patients that are doing the best are the ones that are able to kind of handle the adverse uh effects of some of these drugs. And so you could imagine that if it-

Laura Reiley:

You mean emotionally or you mean just the no —

Glenn Simmons, Jr.:

The actual biological effects. So some of these drugs can significantly, you know, take a toll on your ability to just maintain, you know, just normal metabolism in your body. And so some people might be on the brink of being able to deal with that and others might.

Laura Reiley:

Are you talking about weight or is it much more complex than that? Are you saying that people who are, you know, go into cancer treatment super thin may have a more tenuous or just more fragility or?

Glenn Simmons, Jr.:

Well, again, you know, the idea of weight or even BMI, it's a very, very useful measure if you can't get a hold of anything, right? If you have nothing else to go on. But we realized that it doesn't give us a real idea of what's happening at the molecular level, at the cellular level. And so, for instance, you can have an individual who was an athlete their entire life, they're gonna have a high BMI because they just happen not to be that tall, but they're full of muscle, right? So they're heavy, but relatively short. And then you have an individual who has a low BMI. but they're also not healthy because they may not have enough of the key things that their body needs to kind of, again, maintain their body when their body's in a critical state. And the idea of getting sick, whether it's infectious disease or even malignancy, is that it's gonna take a toll on your body and your body needs energy in order to ramp up that response. And if it's on the brink of just maintaining where you currently are, that could be a major problem.

Laura Reiley:

oh, wow I mean, is a fascinating thing. So what are some of the hurdles in studying this? I imagine. How do you study this and how, you know, what does a control group look like and how like what? So what are the challenges in studying this?

Glenn Simmons, Jr.:

The main challenge is finding an appropriate control group, right? Because many times when you're thinking about things that are involving lifestyle and how people do things every day, you can't really kind of tell people, okay, we're going to put you in a box and we're not going to let you out for 30 days. You know, the idea of even doing something that involves an individual's diet, like maintaining diet life.

Laura Reiley:

We lie, we all lie. I mean, we lie to ourselves about diet. Well, and observational studies like this just tend to not be that useful, right? Or are they?

Glenn Simmons, Jr.:

Well, they can be useful, but again, they're very difficult to actually execute. It's the execution part that's difficult. And so we think about that just on the more clinical trial side of things, but also with the experimental side, like how do we do these things in vitro? And so that they actually replicate what's happening in an individual. And there's a lot of new ways that we can go about that. Our laboratory is exploring some of those right now, but it's not really common. And so you kind of have to push. ah against the grain of what's been done before to establish a new method of doing some of these things. And that's what we're trying to do.

Laura Reiley:

So if you are doing these kinds of experiments and you're, you're trying to reach underserved populations, how do you reach out to them and how do you, how do you get there?

Glenn Simmons, Jr.:

So one of the main things I think is just making yourself accessible as a normal person in that community. One of the things that I always do when I'm doing any community-based participatory research is that I establish that I'm not from here. I know that I'm not from here, but I want to bring whatever is your condition, I wanna bring it to the forefront of whatever resources that I have access to. And so it's really about developing a partnership. early on before there's any talk of we're gonna do this study, we're trying to do this research, we just wanna understand, what's happening here? Just because I'm curious, I think being curious is the first thing that has to be done. And so work that I've done in the past, like in Minnesota or in the mid-south in the Tennessee area, always started with that approach to understand, well, what is it that you're interested in? Because I may have an idea, but it may be completely misaligned with what is important to you in this particular community. And that's the first step.

Laura Reiley:

Yeah, you mentioned Minnesota. I'm interested. I know this is a little bit of a tangent, but I'm interested in the experiment that or the work that you did in Minnesota on predictive on COVID and predictive, uh you know, measuring water, basically.

Glenn Simmons, Jr.:

Yeah, yeah. That was where necessity is the mother of all invention. So during that time, I was still running a small cancer biology lab in Minnesota at the university there. And what ended up happening was that as the pandemic became, you know, a uh reality for us, most of the laboratories, most of the institutions shut down. And I thought to myself, What can I do? I'm a biologist. This is a biology issue and there's a certain amount of public health involved. What can we do here? And what can we do in this little small part of the state? Because our lab again was in a smaller part of the campus where we didn't have a hospital. So we weren't part of the clinical response. We looked at a couple of studies that had talked about the idea of doing surveillance, utilizing wastewater. And from there, I had this almost eureka moment where I thought, but we could probably figure out what's happening at a population level just based off the life cycle of this particular pathogen because we In the wastewater. In the wastewater because we knew it was there.

Laura Reiley:

Cool. I know, I mean it's gross, but so cool.

Glenn Simmons, Jr.:

Well, the gross part, you can't you can't get around that. But eventually you kind of see the utility. And it was from there that we were able to kind of pitch this idea. And it became a community engagement process because we were in we were in conversation on a weekly basis with parts of Minnesota that I had never actually been.

Laura Reiley:

But Minnesota is interesting because it's kind of the gold standard for epidemiological. Like the state is kind of, if every state tracked things as well as Minnesota, the CDC would be in a much better position, right? I — isn't it? I just remember reading about.

Glenn Simmons, Jr.:

Honestly, I was impressed when the actual governance, you know, of the state came to the table and they were talking with the leaders within the university. And, you know, I was being brought into these conversations as well. And it was like, ooh, this is a lot. Because as a scientist, we tend to just get used to being in the background and not really being in this kind of almost like something out of a movie where all of a sudden you're called into this room.

Laura Reiley:

Well, it was. It was like an all hands on deck kind of moment.

Glenn Simmons, Jr.:

Yeah, for a lot of scientists. And they really immediately, once they realized that what we did worked and it worked in a different way than any other laboratory was doing it at the time, they threw all the resources they could behind us. And at that time I ended up having more than one laboratory to maintain, to get the thing off the ground and to get it running. And when we started, we started with the city we were in at the time. We expanded up to about, about 20 cities. And then by the time I decided to relocate, we were up to about 44 cities.

Laura Reiley:

Amazing. That is fantastic. Alright. So I know for a lot of podcast listeners, they're looking for that life hack, that one weird trick, right? And I know you're not going to cure cancer right here from the studio, but I, I'm wondering if you do have suggestions or guidance for people in terms of, uh A, things they can do that may be prophylactic or protective. in terms of your overall health and well-being. And then also, when you have had a diagnosis, what kinds of things can you do to, to uh maximize a positive outcome?

Glenn Simmons, Jr.:

What I will say, and this is probably more and not to the research that we do, is that I think having a diet that is full of as many healthy fats as possible is extremely important and minimizing the sugar.

Laura Reiley:

Where do you come down on uh seed oils?

Glenn Simmons, Jr.:

Hmm

Laura Reiley:

RFK Jr. is not so fond, not so fond.

Glenn Simmons, Jr.:

It obviously depends on what that actually means. So again, as I mentioned before, olive oil is a very healthy oil, monounsaturated fat. So unsaturated fats, minimal processing. So the extra virgin olive oil as it were. Uh. There's studies for, at this point within modern science, decades of research that indicates the health benefits. The so-called Mediterranean diet is well established as being overall healthy for individuals. But having that incorporated into your diet on a regular basis, I think is just really important. And minimizing sugar. One of the things that we looked at in our laboratory is that over, I would say probably like the last 50 or so years, the amount of sugar in the Western diet has just progressively increased in things that you wouldn't even think about. But the other side of that is that that was almost in direct response to minimizing fat. So fat was kind of made into the bad

Laura Reiley:

low fat yogurt with the — with a sagillion grams of sugar in it and we all quit smoking —

Glenn Simmons, Jr.:

And now we're addicted to sugar. Exactly. So I would say that would probably be the number one thing aside from regularly. It's the good fat and uh stay active.

Laura Reiley:

Okay, alright, that sounds great. I guess also I'm interested in kind of navigating the medical world. I think a lot of people are, especially when everyone has someone in their family who's had a cancer diagnosis, what are the things that you can do to um navigate the system or to advocate for yourself?

Glenn Simmons, Jr.:

That's another thing that like my research kind of goes all over the place. And so we actually have had research in that space as well, where what we realize is that communities start to get disconnected from the healthcare systems in their community. And so it's, again, it becomes a us and them, you know, scenario. And I think what's most important to make sure that you can benefit from the systems is that you have to be engaged with them before crisis. You have to understand who and where before the crisis. And so having a regular uh check-in schedule with a physician or with anyone within that healthcare continuum, obviously dentistry is also a part of that. I think that's the most important thing. And then when possible, have those conversations about what things can't necessarily be done to the highest level, especially for those of us who live in rural or rural adjacent types of communities, because oftentimes those are the folks that, again, that's another major health disparity that we've recognized is that individuals who are outside of urban centers tend to not have access to kind of the, the, the super high tech treatment modalities, or at not. just the ongoing care, even, you know, chemo or radiation. And so being ready for that if it ever does occur because you know there might be programs that are available that you may just need to be prepared to utilize as opposed to being being sprung up on you in the midst of crisis because in that case you know oftentimes just psychologically a lot of times we tend to want to reject those things because we just we're it's too much to take in all at once.

Laura Reiley:

I think that's great advice. And I do want to ask you if you have any book recommendations. I know a lot of us are going to be like, I don't want to read a whole book on cancer. But is there anything that's?

Glenn Simmons, Jr.:

um that is more related to science in general. I wish I wrote a book. I would recommend my own book.

Laura Reiley:

Sure.

Glenn Simmons, Jr.:

The Emperor of All Maladies.

Laura Reiley:

Oh I love that book. Yeah. Yeah, sure.

Glenn Simmons, Jr.:

I think it's one of those that kind of, again, just brings a lot of people, you know, into uh a sobering mindset about the reality that some of these things we've been dealing with for a long time. What we're dealing with now is more of an issue in relation to cancer is an issue of frequency. But the idea of solving it is going to take a lot more than just, you know, again, one magic drug, one.

Laura Reiley:

No, it's gonna help us write papers on it perhaps, but that's about it. Well, alright, we are out of time, but thank you so much. Thank you so much, for having me You've been listening to Research Matters from Cornell University. If you'd like to learn more about Dr. Simmons's work or the Simmons Lab, visit the College of Veterinary Medicine website at Cornell. I'm Laura Reiley. If you like this episode, subscribe wherever you get your podcasts and share it with a friend who loves facts as much as you do. Thanks for listening. And remember, when research meets purpose, we move a little closer to a healthier, fairer world. Thanks so much.