With nonalcoholic fatty liver disease affecting nearly a third of the US population, Luma Melo, University of Pittsburgh, describes how mouse studies have shown that low-impact exercise can help reverse liver damage. Dr. Melo also shares with co-hosts Anne Chappelle and David Faulkner how research funding works in her native Brazil and the role of Brazilian women in toxicology.
About the Guest
Luma Melo, PhD, University of Pittsburgh, started her scientific career in her native Brazil, earning a master’s degree in physics from the University of São Paulo, where she also served as an Associated Instructor. She then earned a master’s degree in the philosophy of science and medicine and a PhD in environmental health from Indiana University in the United States.
Dr. Melo’s research focuses on liver disease (both alcoholic and nonalcoholic fatty liver disease) and exercise. She is exploring mode of action and genetic expression related to how exercise and environmental chemicals modulate the development of nonalcoholic fatty liver diseases, as well as liver fibrosis and the mechanisms and determinants of mortality of alcoholic liver disease through translational studies including human samples and experimental models of liver disease. She also has conducted research involving aerobic exercise and breast cancer and published a book on quantum physics for laypeople titled But After All … What Is Quantum Physics?
Dr. Melo is currently a Postdoctoral Associate at the University of Pittsburgh Medical Center and an Adjunct Professor with Ball State University.
[00:00:00] Adverse Reactions “Decompose” Theme Music
[00:00:05] David Faulkner: Hello, and welcome to Adverse Reactions Season 2. My name is David Faulkner, and this is my co-host,
[00:00:11] Anne Chappelle: Anne Chappelle.
[00:00:12] David Faulkner: As much fun as the first season of Adverse Reactions was, I think Season 2 is better.
[00:00:16] Anne Chappelle: Hidden.
[00:00:17] David Faulkner: Secretive.
[00:00:18] Anne Chappelle: Exactly.
[00:00:19] David Faulkner: The toxicology that happens when you’re not looking,
[00:00:22] Anne Chappelle: or toxicology that you forgot about.
[00:00:24] David Faulkner: It’s still important, and we’re here to talk about it. Welcome to Season 2 of Adverse Reactions:
[00:00:28] Anne Chappelle: “Hidden Toxicology.”
[00:00:31] Adverse Reactions “Decompose” Theme Music
[00:00:38] David Faulkner: Sweating It Out: Exercise versus Toxic Exposures.
[00:00:41] Luma Melo: It’s actually not a high-level exercise. We’re just considering regular people that don’t have time. And sometimes you have other diseases also, co-factors, so we want everybody to be able to exercise and have the benefits.
[00:00:53] David Faulkner: Or, Luma Melo Makes Us Walk:
[00:00:56] Anne Chappelle: How Exercise Affects Things Like Cancer and Liver Disease.
[00:00:59] Luma Melo: Fatty liver disease doesn’t have necessarily to be caused by the diet. It could be caused by chemical exposure. So, chemicals that we’re exposed to all the time through the water. And sometimes, yes, you are doing all the right things and you’re still being exposed to things that were just hard on your body.
[00:01:13] Adverse Reactions “Decompose” Theme Music
[00:01:17] David Faulkner: Hello, and welcome to the Adverse Reactions podcast. My name is David Faulkner, and I am joined today by my delightful co-host, Anne Chapelle. We are joined today by our guest, Luma Melo. Thank you very much for joining us.
[00:01:27] Luma Melo: Thank you for having me. I’m excited about this.
[00:01:30] David Faulkner: Tell us a little bit about yourself and a top-level view about work you’ve done with exercise and tox.
[00:01:35] Luma Melo: So, I’m Brazilian, and in Brazil, we play soccer a lot. So, I was raised in a very active way. I’ve always played sports. I actually played in college, at the university level—I played rugby and also basketball. So, I always liked that. I always had that in my life. But then, I had to choose between going to professional basketball or going into university. Because in Brazil, we don’t really have these kind of scholarships, like here in the US, where you can study but also practice your sport. So, I chose becoming a scientist and go for the education path.
I actually did my undergrad in physics and then my masters in biophysics. So, I was not aiming to do what I do right now, but I just inside of me, I just kind of liked this so much, sports. And on top of that, nowadays, I work specifically with the liver. My mom had hepatitis when I was young; she had a 20% chance of living. She was the subject for a drug test that saved her, basically. She would get one shot a month that was shipped from the US to Brazil. So, I started with physics and biophysics, and then I even did a master in philosophy of science.
My path to what I do right now is very not traditional at all, but it was funny because now, I do something I love and I have the liver, it’s like I’m doing research for something that actually my mom had, and the exercise that was always in my life. So, that’s how I got to do what I do.
A big person involved in that is Dr. Amit Hagar. He’s a Professor in the Indiana University, and he was the one, actually, that got me really into the exercise. And I actually met him several years before I started my PhD with him. In Brazil when I gave a talk, he was there visiting. He just needed someone, and I loved the subject.
[00:03:11] Anne Chappelle: So, I find that interesting that you were able to make a connection, and I’m assuming that he was doing some of visiting scholar kind of thing? But this idea that you met this person, you had a good connection, and you were able to find a path forward together and come to the US. Because I was wondering how you got to Indiana from Brazil. It took a leap of faith for you to come to the US.
[00:03:36] Luma Melo: Yes, a lot. It was really a leap of faith with everything: with that city, with the university, with him. And actually, later, I ended up also working with Dr. James Klaunig, and that’s the connection with SOT and toxicology. He was the one that introduced me to all of that, but I was only introduced to him because of Amit Hagar.
[00:03:53] Anne Chappelle: Which brings me to this connection: I was realizing when I was looking at your research that we’ve met before.
[00:04:00] Luma Melo: Oh wait, in the dinosaur museum?
[00:04:03] Anne Chappelle: Yes, at SOT.
[00:04:05] Luma Melo: Yes.
[00:04:06] Anne Chappelle: You were with Jim Klaunig, who I’d known. We were talking, and you’re the only Brazilian toxicologist I knew, so I said, “Wait, I know one other Brazilian toxicologist and introduced you to Monika.”
[00:04:21] Luma Melo: Yes.
[00:04:22] Anne Chappelle: This whole idea of networking and strong women and just finding somebody else that could make you feel more comfortable or able to chatter with in your own native language.
[00:04:35] Luma Melo: I have even more connections because after you did this—that I completely forgot and I’m so happy reminded me of that—I was more into the Women in Toxicology session, and actually, I ended up meeting a lot of Brazilians in that Women in Tox. And I ended up interviewing them because I noticed I was reading the history of toxicology just for fun.
[00:04:55] Anne Chappelle: Just for fun.
[00:04:56] Luma Melo: Just for fun.
[00:04:57] David Faulkner: As one does.
[00:04:58] Luma Melo: And I thought, I don’t know the history of toxicology in Brazil. Then I started reading about it. I saw there’s not much out there. And I noticed, which is very interesting, is that it’s a new area there. So, the people that actually started, they are still alive, which is amazing. And not only that, but the ones they started, they’re mostly women. So, nowadays, more problematic, not necessarily most are women, but the ones that started were mostly women. And I interviewed them. And then I wrote a paper that is there now, it’s published, about these women. It was very nice because I was able to talk to all of them. All of them are part of Society of Toxicology, so we’re able to exchange a lot of things. So, again, you see, one thing leads to the other, leads to the other. It’s amazing.
[00:05:39] Anne Chappelle: So, you’re a part of the Hispanic Organization Toxicologists. I think they abbreviate that HOT?
[00:05:45] Luma Melo: Yes, I am, yeah, proudly.
[00:05:46] David Faulkner: Proudly HOT.
[00:05:47] Luma Melo: Proudly HOT. No, it’s a great, I think on the Women in Toxicology, the HOT, and also the Carcinogenesis session, I think these are the ones that really helped me with networking and opportunities—work opportunities and even just personal relation. As you say, like finding someone that speaks your native language or have experiences similar to yours, working in the same field. It’s super nice. SOT’s been a blessing.
[00:06:12] David Faulkner: So, let’s dig in a little bit into the work on exercise and physiology that you’ve got here. It would seem that you are in favor of exercise, broadly speaking. For me, I’m like egh, but you like it.
[00:06:24] Luma Melo: I think the part that I most like about the method that me and Amit developed is that it’s not a hard activity you have to do. It’s basically when you translate to humans the amount, the quantity, those of exercise that we use for those animals is actually the equivalent of a fast walk, 30 minutes, five days a week. So, I’m not telling everybody, go to the gym and do the weights or run for an hour. It’s not a big thing. Just be more active, basically. And the good part is that we did all of this researching on alcoholic fatty liver, which is a very prevalent disease; around one-third of the population of the US have it.
[00:06:59] David Faulkner: Really?
[00:07:00] Luma Melo: Yes, it’s mind blowing, when you think about that. Yes. Because it’s not necessarily you have symptoms and not necessarily you’re overweight. A lot of people, they’re thin, they also have fatty liver. And there are different causes for it. We focus on diet, and more specific, high-fat diet, which we call the Western diet. It’s like a fast-food diet. But there are other causes. It could be genetics. It could be some sorts of chemicals that could cause that. There’s so many things that could cause the fatty liver. But it affects one-third of population, and there’s not really a cure because all the drugs that were tested, in the end, they caused some kind of toxicity. So, actually, exercise, it’s believed to be the only therapy for it.
You can’t really do exercise experiments in vitro, but then you see with the animals, the traditional models we have, either cause a lot of stress or they’re not translatable to humans. The one that best translates to humans from traditional models, it’s a model that you put the animal in a treadmill and you just make them run as much as it can. And the good thing about the treadmill is that you can control the velocity, the time that they are there, so you control the dose of the exercise. But to make them run in that way in the treadmill and in a high-level kind of exercise, the methods that are used to stimulate them to run that way is either electrical shocks or poking.
[00:08:19] Anne Chappelle: Which is exactly how I end up running, is that I end up being poked or—
[00:08:28] David Faulkner: Or electrocuted?
[00:08:29] Anne Chappelle: That’s really the only way it really works for me, either, because—
[00:08:33] Luma Melo: And you love it, right?
[00:08:34] Anne Chappelle: You know, it’s something I look forward to every single day.
[00:08:38] David Faulkner: OK, so, you’re not poking the animals, you’re not electrocuting them.
[00:08:42]Luma Melo: Not poking, no.
[00:08:44] David Faulkner: OK, good.
[00:08:45] Luma Melo: So, we’re not doing this. What Amit came up with and then afterwards I just helped him develop a little bit further is that we also use treadmills, but we put wheels on top of the treadmills. And the mice, they like the wheels. They like the shape. Our protocol is just increase the velocity very slowly. So, we do a whole acclimatization where they run very little, for five minutes and then 10 minutes. So, it’s not, we put them 30 minutes in velocity X; we just slowly increase. So, every minute, we increase a little bit, and we progress those velocities in the weeks that we’re doing the training. So, it’s a very slow incrementation of the velocity. And not only that, but if they refuse to run, normally they run very well, but there’s always one or two that they are rebels and they are like, nope.
[00:09:31] Anne Chappelle: That is the rat that’s named “The Chappelle Rat.”
[00:09:34] Luma Melo: There you go. What we do is just decrease the velocity a little bit—basically, give them time to breathe. You know, it would be equivalent to us, you’re tired then you just decrease a little bit, drink the sip of water, and then come back to it. It’s the same thing, so we just lower the velocity a little bit and then slowly increase again. And they just run. That works perfectly.
It’s actually not a high-level exercise. We’re just considering regular people that don’t have time. And sometimes you have other diseases also, co-factors, so we want everybody to be able to exercise and have the benefits. That’s one of the things we had in the back of our mind. So, given that amount of exercise, we actually show for the non-alcoholic fatty liver disease, just that amount of exercise actually was able to completely revert the liver. So, basically, your liver is sick; you have a lot of fat accumulation, inflammation, you already have fibrosis, you have non-alcoholic fatty liver disease. And then just with 10 weeks of this exercise program, you completely changed your liver to a healthy one.
Now, one thing, all the markers you’re seeing the disease was completely reversed only when you have the exercise with the change of diet. So, that will be, basically, a person goes to see the doctor, the doctor says, “You have fatty liver, you have to take care of yourself,” and that person changed their lifestyle—change the diet and starts to exercise. We did another intervention where you don’t change the diet at all. You continue eating the fast food, but you exercise. For that group, you do see benefits. You do see fat content decreasing. You see a little bit less inflammation, a little bit less fibrosis, but your liver is still sick.
[00:11:06] Anne Chappelle: Let me just make sure I understand. So, this was in mice.
[00:11:10] Luma Melo: Mice, yes.
[00:11:11] Anne Chappelle: But you haven’t demonstrated this fully in humans yet.
[00:11:14] Luma Melo: Not yet—hopefully soon.
[00:11:15] Anne Chappelle: I just wanted to make sure because I’m not quite ready to give up all those things, but I have a good friend who passed from multiple myeloma a few years ago. She took really good of herself, and she exercised of the time and did all the regular stuff. So, how do you come to grips with that against if you exercise regularly, that’s healthy? Because then your body really is turning on you, and you’re like, damn it, I should’ve had that donut.
[00:11:42] Luma Melo: Fatty liver disease doesn’t have necessarily to be caused by the diet. It could be caused by chemical exposure. So, chemicals that we’re exposed to all the time through the water. And sometimes, yes, you are doing all the right things and you’re still being exposed to things that were just hard on your body. I understand the frustration.
[00:11:57] David Faulkner: Well, this gets at what I think is a interesting question. So, you’ve showed that there’s a connection between diet and exercise and fatty liver disease. Diet is something that we can control, but what about things that we can’t control? Is there any evidence that exercise affects the resistance to other environmental exposures or contamination?
[00:12:15] Anne Chappelle: Yeah, if I’m not running outside, I’m not being exposed to that particulate matter, so it’s healthier for me to sit on my couch.
[00:12:24] Luma Melo: And eat that donut. So, I actually read research on how exercise helps the body clean itself from a certain chemical, then prevent. So, we do know that it helps with, for example, the immune system. And it does keep your metabolism, at least in the liver, strong. So, when you are exposed a chemical, your body will deal with that kind of a chemical a little bit better than if they’re not healthy. But most of the research is more on how exercise helps clean that toxic out of your body faster than not.
[00:12:57] David Faulkner: Through, like, circulation, right? You have improved circulation?
[00:12:59] Luma Melo: Yes, more or less.
[00:13:01] Anne Chappelle: Well, you could have better metabolic enzymes. You could have other positive inductions.
[00:13:06] Luma Melo: Yes, exactly. I think it’s more on metabolism than anything else. But it does help circulation, for sure.
[00:13:11] David Faulkner: OK, because my initial thought was if exercise helps cope with disease and things like that, then Olympic athletes have got to be immune to most toxins, at that point.
[00:13:20] Luma Melo: But it’s funny you say that because there is a right dose because actually can exercise be a stress to your body and can actually be harmful. The dose makes the poison. So, with exercise, it’s the same thing. So, with exercise, there is a level that is actually stressful and harmful to you, and those elite athletes, they are above that dose.
[00:13:38] David Faulkner: So, this is something else I was wondering, too: Is there a difference between the sexes? Did you see male mice versus female mice with the fatty liver disease, or?
[00:13:45] Luma Melo: I still have to do more on the different sexes, but there is such an interesting different in the gene expression and just metabolism in general between the female and male in mice. Just in general—so without the exercise, without any intervention, without diet—if you just analyze the livers from a female and a male mouse, it’s completely different. And then also exercise affects the genders differently. The female mice, they are better in running long distance and for a longer time, when the male mice not. So, just for that, that difference in the way they like to exercise or endurance of their muscles, just that already gives them a different effect. Because again, it’s like the dose of exercise is different for them. You just see naturally, intrinsically, the difference in their livers and then also they were running different ways, so you will see different response to that. But in general, it is the same once you get the fatty liver and you exercise them, you still see the benefits.
[00:14:38] Anne Chappelle: So, I have to ask: Are you thinking one day about going back to Brazil? You’ve got a lot of female role models there, strong toxicology, mild winters.
[00:14:50] Luma Melo: Good food.
[00:14:51] Anne Chappelle: Good food.
[00:14:52] David Faulkner: Great dancing.
[00:14:53] Luma Melo: Good dancing.
[00:14:55] Anne Chappelle: Having an opportunity to go back to Brazil, do you think it’s quote unquote easier to do research, potentially, in Brazil because of the way it’s funded or the way that it works versus the US?
[00:15:08] Luma Melo: It is completely different, and I don’t know if it’s easier or not. Here, everything is grants, and if you don’t have a grant, you’re nothing; there’s no way you can do your science. There, not necessarily. The university give you the condition. So, not necessarily you need grants. You can have extra grants if you want, but the universities give you conditional lab to work. And not only that, but in Brazil, we do have public, full public, a hundred percent free education. It’s actually the best universities, they are the free ones.
It’s a good system in a way that the government is constantly funding not only the university, like the teaching, also the research. So, I love that system, and I think it works better. I think the scientists more free and less stress, more relaxed. I feel like here, there’s a lot more tension and pressure, but there’s also the bad side, which is if the government at that time it’s not funding or don’t think science should be funded that much or thinks the funds should go to another area, then science lose, and that’s what has happened. That’s why I left Brazil. If it was for me, I would never leave Brazil. I love my country. And yes, the first opportunity I can to go back, I would, not even thinking about it, but I left because that one was happening.
The government at that time, actually, they were taking away the funds from science. All my friends are back there, just not being able really to do much, just waiting until we have government that gives the funds back, which is very sad. But yes, if it was for me, the first opportunity I would have, I will go. I really like, here it is so easy in the US, just because yes, once you do have the grant and you do have the money, you can do so much so fast compared to Brazil, because most of the things we import from the US so it takes more time, it’s taxable, blah, blah, blah—from reagents to equipment, it’s easier in that way. Now, we just have everything here and the US is so good at doing science and technology; if there’s one thing you guys are good, it’s definitely that. And for me, so good to come and learn. Not only that, but the science here in the US is so international. So, you just see all these people from all these different backgrounds. And I think this is amazing. It’s something, if I stayed in Brazil, I wouldn’t have, and I wouldn’t learn as much as I do here and I did.
But still, it’s my country and I really love it. And I do feel almost the obligation of coming back. I did get free education. I did go to the best in the country, the university, and got my undergrad and my masters there. So, I almost like I do have to, at some point in my life—it won’t be soon, unfortunately—come back and do something for the country.
[00:17:35] David Faulkner: Yeah, that makes sense. You talk about how you took this winding road to get to where you are right now in terms of what you’re doing. And just looking at things that you’ve written, it’s an incredible range; you wrote a book about quantum physics, and I think we should address that because it’s very, it’s a great book; I really enjoyed it. But you also have this history of women in toxicology in the United States in addition to Brazil, and a paper about—I love the title of this—“Psychosomatic, as We Know,” which my understanding of it, it seemed like philosophy of science, philosophy of etiology of disease. How do you manage having so many interests aside from just writing everything, it would seem?
[00:18:12] Anne Chappelle: How do you have time to exercise? I think is what David’s asking, because clearly you must have like a treadmill, a non-prodding, electrified treadmill, with a keyboard in front of it.
[00:18:25] David Faulkner: Or a Dictaphone. It could be she’s dictating.
[00:18:28] Anne Chappelle: You’re quite prolific.
[00:18:30] Luma Melo: Yes, my wife jokes a lot about how I just do a lot. I just like that. I think, I don’t know, it’s in me. I don’t know how I do have the time. I think I’m fast. I write fast. It was not like I was born like this; it just, I just developed that. This is a blessing but could be hurtful because I do see, now I’m writing a grant, I do see that this is one of the things they evaluate—how much I publish exactly in the topic that I’m asking the funding for. And sometimes I do look back on my CV and I’m like, “Well, I’m all over the place. I don’t have one thing that I worked my entire life.” So, that could hurt me. So, I do see the bad side of that. But I love that; I love it because it doesn’t get boring, and once I get stuck in one thing, I just go and do this other thing in this other area. And then, I like that, actually.
[00:19:32] Anne Chappelle: In looking through a lot of the things that you’ve written, it’s written in a way that everyone can understand. That takes a lot of skill to be able to translate a complex topic into something that my mom is going to read this book on quantum physics and understand. And I love the beginning of your book as well, that you really explain why you’re doing this and how you’re driven for it, and recognizing not just the big names but the people that built the science for the others stand on. And that’s a wonderful model. So, is there a question in there? What other things were good models for you to learn how to write this way? Could you talk a little bit about your passion for communicating?
[00:19:59] Luma Melo: That’s interesting. I never thought of this. Everything I write, I just do force myself to write in the simplest way I can. I actually had to learn how to write in a not simple way because my brain just go towards that naturally. I don’t know if it’s because I’m the first scientist in my family. There is one other biologist, but she’s more like a lab tech, she’s more in the technical side of it. I’m the first doctor in my family, the first one to even go to grad school. So, I think maybe because I was brought up in this family where my father never even finished elementary school, my mom also have incomplete studies, I wrote that book so my parents would, my family would understand what I do. The quantum physics book, my mom still reads it, and then she’s like, “Well, I did not understand this. I need to go.” And then she comes and asks me questions. So, it was not simple enough, yet. Maybe it was because of that.
But also, I do have in the back of my mind the entire time that we are doing science to develop the world, humanity, to diseases. But if we just do that and don’t share that with the world, the rest of the population, they need to see this disparity. This small elite of scientists are developing themselves and humankind, and they are progressing, but then we’re leaving all this other people behind that don’t have the privilege or don’t want to go through the training to understand these things. I always keep that in the back of my—I actually wish I did more. But I think we scientists have a lot of knowledge; we just keep it to ourselves.
[00:21:22] David Faulkner: It’s true. We’re getting close the end of time. We have a couple of questions we’d like to try to ask everybody, and it’s always interesting the responses we get. Anne, would you like to start with this?
[00:21:31] Anne Chappelle: Yes, and I’m afraid, actually, to ask this question, Luma, because I can only imagine how many of these you have. So, I was wondering what your hidden talent is?
[00:21:42] Luma Melo: Oh.
[00:21:44] Anne Chappelle: Besides rugby.
[00:21:46] David Faulkner: Astrophysics.
[00:21:47] Anne Chappelle: Astrophysics and quantum physics and multiple languages.
[00:21:51] David Faulkner: Philosophy.
[00:21:53] Luma Melo: I mine is actually painting. I like to paint a lot, and I do it a lot, and I like the watercolor. I had no technical training, so I just do whatever I want, but I wish I did have because my brain is wanting to do one thing but then when I try to do it, my body, my hands, don’t go the way that I want. But yeah, I do the painting. I love it. I just give everybody paintings all the time. And in my house, all the walls have the paintings that I do.
[00:22:15] Anne Chappelle: That’s awesome.
[00:22:16] David Faulkner: That’s really great. So, we always have to ask, what is the most significant adverse reaction you’ve had in your life?
[00:22:21] Luma Melo: I was luckily born in, at that time, wealthy family, but then we lost everything very quickly, very fast, so I just found myself in a teenager phase losing everything. And then I had to start working early to find my own path to life because I just kind of have to fight myself through whatever I wanted to do. And that worked well, actually. I was able to do it. But also, I think I was able to do it because I have the advantage of having an early very good education, being exposed to English. I started learning English in 10 years old, and that was because they had the conditions to give me that. But I think that was the hard one, just finding myself young and that everything needs to shift. So, in the end it’s a good thing, taught me a lot of good things. I wouldn’t change anything.