Just Like Nana

Dr. Frances Champagne

• Amie Penny Sayler • Episode 13

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In this episode of Just Like Nana, host Amie (Elizabeth) Penny Sayler is joined by Dr. Frances Champagne to delve into the world of epigenetics to discover how your environment and experiences shape your brain and behavior. 

This episode explores how understanding these interactive pathways can actually lead to greater resilience and personal agency, regardless of the past. 

About Dr. Champagne

After completing a B.A. in Psychology at Queen’s University (Canada), Dr. Frances Champange delved into the genetic and environmental risk factors in psychopathology at McGill University in the M.Sc. program in Psychiatry. She then started a Ph.D. in Neuroscience at McGill University examining the role of mother-infant interactions in shaping the brain. In 2004, Dr. Champagne received a fellowship from the Canadian Institutes of Health Research to conduct postdoctoral research at Cambridge University (UK), examining the role of imprinted genes in development and social behavior. From 2006-2017, She was a faculty in the Department of Psychology at Columbia University and established a research group examining the epigenetic influence of early life experiences. Her interests focus on the interplay between genes and environment that shape neural and behavioral outcomes and the implications of this dynamic interplay for inheritance of traits. 

In This Episode, You’ll Learn:

  • Research shows that the quality of maternal care doesn't just affect the immediate offspring; it shapes the brain systems of generations to come.
  • Beyond pure biology, trauma can be transmitted through family stories and learned behaviors, which eventually become "embodied" in our stress systems and nervous system reactivity.
  • Despite the potential for transmitting stress, the most common biological response to adversity is resilience. Because the epigenetic system is designed to be malleable, there is always room for change and intervention.

Resources Mentioned

Connect with Dr. Champagne

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Theme music by Carter Penny.

Epigenetics 101: How Our Biology is Rewritten Over Generations with Dr. Frances Champagne

Amie Penny Sayler

Welcome to Just Like Nana. So thrilled that you're here today. Hope you've had the chance, if you have a Nana or Nana-like person in your life, to give her a hug or text her a meme or call her on the phone if she still likes that. Today, very excited to be talking with Dr. Frances Champagne. Dr. Champagne studies the interplay between genes and environment and how they shape neural and behavioral outcomes. She's the Associate Dean of Research and a professor of psychology at the University of Texas at Austin. She completed her BA in psychology at Queen's University in Canada. And then she delved into the genetic and environmental risk factors in psychopathology at McGill University for her master's in psychiatry. She obtained a PhD in neuroscience, also at McGill University, in which she examined the role of mother-infant interactions in shaping the brain. In 2004, she received a fellowship from the Canadian Institutes of Health Research to conduct postdoctoral research at Cambridge University in the UK. There, she examined the roles of imprinted genes in development and social behavior. From 2006 to 2017, she was a professor of psychology at Columbia University, and she established a research group examining the epigenetic influence of early life experiences. In case it's not clear, Dr. Champagne is brilliant. Her research is extensive and varied. Thank you so much for being here today, Dr. Champagne. We're just thrilled to have you at Just Like Nana. Thanks for having me. Absolutely. So excited to talk to you today. You just got such a unique combination of education, experience, your skill set, everything you've done. It will be fascinating to discuss. So thank you. Perfect. We like to start, if you don't mind. And if you don't have a memory, that's fine. But do you have a favorite or powerful memory of one of your grandmas? And what did you call her?

Dr. Frances Champagne

Yeah, you know, it's so long ago. I obviously what I called my grandparents was not something so distinct that it just leaps out at me. Probably knowing myself and my family, it was just grandma and the surname. So they lived quite far away, and it was the before the era of Zoom and uh all these things. So I, you know, saw them at special occasions. I think one of my earliest memories in general is when my younger sister was born because I was sitting in the waiting room with my grandmother as my parents were off busy having my sister. So that kind of resounded that kind of safety and and feeling like, yeah, this is this is part of my broader family.

Amie Penny Sayler

So love that. How old were you when your sister was born? Uh two and a half. Oh, wow. Really young. Yeah. Well, that's really special. Can you kind of describe to our listeners your work? It's just, it's fascinating.

Defining Epigenetics and Its Relevance

Dr. Frances Champagne

When I was doing my PhD at McGill University, I was working with a group that was really interested in understanding how how we develop differences in stress. So not everyone is stressed in the same way. People have different risks of mental health. Understanding what creates individual differences in stress responses was a really important interest. I think it still is generally. But I was working with a group that was really interested in environmental factors that shape this. And they'd come upon the role of maternal care. So uh, and this was all studies in rats, but of course, there's a lot of, I think, translational relevance of this work. So everyone was really interested in stress reactivity, but you know, watching these rodents interact with their babies got me really interested. Well, why are the mothers different in their maternal care? That seemed to be a real big trigger uh in these long-term outcomes. But why would there be differences in maternal behavior? And it was fascinating to watch these rats be, you know, taking care of, you know, up to 20 pups at a time, some methodical, but again, a lot of individual variation. And so my PhD then focused on maternal care, how it shaped daughters and their own maternal care. And then, you know, it kept working out, and uh, that granddaughter's maternal care was also shaped by this pathway. So that really, I think for me, cemented the importance of thinking about two things. First, about how these maternal effects can persist over multiple generations, and the importance of mothers more broadly. So mothers seem to have this really profound influence on their offspring and really exploring that. What are the mechanisms, what are the implications? So that was really anchored with my dissertation work. I then went on to do work on genomic imprinting, which is a form of epigenetics, and uh that kind of expanded the different ways of thinking about how mothers shape their offspring and how these effects persist. Uh, and then really kind of expanded when I was a faculty at Columbia and now at UT Austin, how we integrate thinking about different life experiences at different phases. They could be prenatal, postnatal, maybe even later on in life, how those come to shape our health and our brain and behavior, and specifically how epigenetic mechanisms become kind of integrated into this whole understanding of the lasting effects of early life experiences.

Amie Penny Sayler

Can you level set when you talked about epigenetics? How do you define it? How do you see it? What are you looking at?

Dr. Frances Champagne

The term epigenetics, I think, has been used historically in a lot of different ways. So I think probably when I first started doing work in this field, it was generally used to just describe anything that was not genetic. So if you're looking at, you know, identical twins and yet they are different, this would be epigenetics. But I think over time, and certainly the way I think about it now, is really referring to very specific molecular changes that occur in DNA or around the DNA that have a lasting impact on the way your genes function. So not an effect on the sequence of your genes, but really something around that that serves as an on-off switch for gene activity. So in my current research, we tend to focus on DNA methylation. It's a stable chemical modification to DNA, but again, it's also malleable, right? So it's it's kind of got these perfect properties for both understanding how the environment shapes us, but also how these effects might persist over generations.

Amie Penny Sayler

And this is a very crude analogy, but I've heard it before. So is it sort of that the DNA is kind of the hardware? Okay, it's there, but then it can get turned on and off. So there's sort of the software that runs, and that's sort of the environmental factors. I mean, again, I know that's really crude, but if you can kind of describe it in those terms.

Transgenerational Epigenetic Inheritance

Dr. Frances Champagne

I think it's it kind of captures, I think, a lot of the properties. Of course, our capacity to use epigenetics, it's also part of our gene, part of the hardware. So there's this constant crosstalk between that material that we're born with, the DNA sequence, and all the other things we need. You know, our DNA sequence is essential because it's it's kind of the instructions that we need for everything, but we need to be able to adapt and respond to environmental cues across the entire developmental timeline. And so these epigenetic factors are really important for that.

Amie Penny Sayler

Okay. And then as I understand it, and I think what you were describing with the rats is that the epigenetic factors, it's not just directly the mom or the upbringing, or even like you said, prenatal. Those epigenetic factors could be have been triggered by previous generations and it's still sort of carrying down a familial line. Am I understanding that correct? Or how do you describe that?

Dr. Frances Champagne

There's actually a number of ways. So let's say you have three, even four generations of a family, and you see that the experience in the first generation has these effects that persist to maybe the third or fourth generation. So the question is, why is that happening? How is that happening? There are multiple ways for that to happen. And one of them is that you're referring to is this inheritance, as it were, of the epigenetic changes. Now, most of the evidence for that comes from animal studies, because capturing three to four generations in humans is a is quite an undertaking, but working with species that have shorter lifespans allows us to look at this in more detail. And it has mostly been studied in the context of fathers. And this is in large part because when you're studying mammals, particularly, mothers have so much interaction with the baby that you don't know whether it's something they've inherited from a previous generation or something that's being shaped continuously by the prenatal or postnatal interactions that babies and mothers have with each other. So fathers are kind of a nice avenue to study the transmission of epigenetics and the possibility of that, because in most species, fathers copulate with the mothers and they don't engage in caregiving behaviors. They certainly don't gestate the babies and they don't engage in a lot of maternal uh paternal care afterwards. My assessment is that it's certainly possible for these epigenetic changes to be acquired and to persist over generations coming from fathers, but that's not all that's going on. And there and there's many other ways in which these epigenetic and environmental factors can persist over generations beyond just the inheritance of these epigenetic marks.

Amie Penny Sayler

One quick kind of going back, and and I think I know the answer, but when you were describing the work with rats, I'm assuming only the mothers were involved in the care of the pups. That's correct.

Dr. Frances Champagne

Yeah. So very few species actually have paternal care towards their offspring. And most of the species that are studied in laboratories across the world are not biparent. There are some species that are, and then they're kind of interesting to study when you're thinking about these factors. But in general, no. So it's just, it's just the mothers.

Multifaceted Approach to Epigenetics

Amie Penny Sayler

And then you ended by talking about how, okay, this is one factor among many. And this is where your education is so interesting because you're kind of you have a multifaceted approach. So can you sort of explain that multifaceted approach and talk about some of the other factors?

Dr. Frances Champagne

You know, I think phenomenologically, there is certainly this observation that these effects can persist over generations. So when it comes to fathers, everyone's like, well, it must be something that they're passing on biologically because that's all that fathers are contributing in many of the lab studies. But when you have interactions or effects that are coming via mothers, there's actually a lot more opportunities. And even when it's coming from fathers, there's a lot of interaction with these other, these other mechanisms. So we learn a lot from the previous generations, right? So we learn about what to be stressed about. Infants learn how to self-regulate by being around their parents. And so you can see that this, there's this learning mechanism whereby we learn about people's previous experiences, whether they are both positive or negative, and that perpetuates certain behaviors across generations. So with our maternal behavior, we know that the tactile elements of maternal care shape the systems in the brain that will predict future caregiving behaviors. So, in a sense, what you experience shapes the brain systems that will shape your behavior, and that behavior will then shape the next generation. So, you know, we can think about this broadly as learning, but it is epigenetic in the sense that these experiences lead to epigenetic changes in the brain that then shape behavior that then shape subsequent generations. But it's not being inherited in the classic way that we think of inheritance, where something is coming through the sperm and egg, and it's it's kind of there from the get-go.

Amie Penny Sayler

What are the other systems or sort of learnings that we carry forward from our parents? So you're talking about, okay, it's shaping the brain as far as this is what caregiving looks like, this is how I provide this care. What else are we figuring out through our parents? I think you you mentioned like regulation. Is that your response to stress and the nervous system, or how does that play into it?

Neuroplasticity and Its Impact on Future Generations

Dr. Frances Champagne

I think some of the best examples of this are, let's say, trauma or mental health. So when it comes to trauma, if if a generation is experienced a severe trauma, this affects mental health. Mental health can affect stress systems and neuroplasticity and many other things in the next generation. And we know we we kind of think of this as stress programming, right? So the stress of one generation programs, you know, through through, again, the stress they uh are observed to engage in, the mental health costs of that stress, then shape the experience and the stress systems of the next generation that can be perpetuated. We can also think of trauma narratives that can persist in family lines. And this has been something that's been explored increasingly, I think. And again, from kind of more of a psychological, sociological perspective, whereby when a generation has trauma, that becomes part of the narratives, part of the stories that they tell to their children, to their grandchildren. And that becomes, in a sense, embodied in brain systems and stress systems and leading to this kind of increased stress reactivity. And so I think those are kind of two different ways of thinking about these kind of learned but kind of experience-dependent transmission over time.

Amie Penny Sayler

You mentioned neuroplasticity. Can you sort of describe that? And I my ears perked up when you said it actually affects the neuroplasticity of future generations. Can you talk through a little bit of what that means?

Dr. Frances Champagne

Our experiences shape all sorts of things. So, you know, in my lab, we study, you know, everything from endocrine disruptors to stress to adolescent social isolation. Generally, most of these experiences affect how changeable our brains are. How, how, and it affects our capacity to learn. And there's probably some sort of adaptive element to that, right? So, you know, we're we've got experiences that our brain systems need to be aware of that need to change in response to. And so systems in the brain that are important for learning and memory, for cognition, they're all going to be responsive to a lot of different cues in our lifespan. Neuroplasticity ultimately is determined by the turning on and turning off of genes. And so when there's experiences in generations such as trauma or, you know, enriching experiences, that's going to have these kind of broad spectrum effects. It's going to affect stress, but it's also going to affect, you know, how malleable these brain systems are. And that's that's kind of captured in neuroplasticity.

Amie Penny Sayler

Interesting. A little bit of what I'm hearing is so there's perhaps this epigenetic and other factors carrying on this stress response. And then you layer on top of that perhaps some not as malleable or not as easy to kind of change that stress response. So you're kind of, you know, in some ways experiencing the double whammy of the effect, if you will.

Endocrine Disruptors and Their Effects

Dr. Frances Champagne

Absolutely. And I think we're really interested now in the double whammy. And I think more broadly, let's say we're doing a study in animals. And again, they're the best evidence of this inherited epigenetic change. To show that it is inherited like that, you have to remove all the other sources of variation that might account for that effect. But in reality, we are constantly being exposed to all these. We are, you know, we have all roots we're being exposed to. And so when you think about why, in some grand offspring, great-grand offspring generation might see this or not, it's probably the fact that in some cases there's the combination of all of these factors. When we look, for example, at prenatal endocrine disruptors and their effects, we tend to find that we see those effects only if, or more robustly, if there's also been additional stressors or decreases in maternal care. So these other rout serve to reinforce and enhance some of these vulnerabilities that might be acquired from previous generations.

Amie Penny Sayler

When you talk about the endocrine disruptors, what are you, what are you looking at in that work? And what does that mean?

Dr. Frances Champagne

Endocrine disruptors kind of describe a broad range of chemicals in the environment that disrupt how our endocrine systems work. So our stress systems, our steroid um hormone systems, so estrogen, testosterone. Many of the chemicals that are used to make modern products have these endocrine disrupting chemicals in them. I study mostly bisphenols, which are used in the manufacture of plastics. And there's a lot of interest on the long-term effects of these endocrine disruptors. So, for example, BPA has these lasting epigenetic effects. It can even have multi-generational effects. Now, a lot of plastics have replaced BPA with other bisphenols. And uh in reality, we're being exposed to a lot of different chemicals. So we have been exploring these mixtures of chemicals for a long time. And it ends up, yes, you can see these long-term effects, but you're going to see them more likely if there's also postnatal adversity or reductions in maternal care that then serves to accentuate these effects.

Amie Penny Sayler

I'm going to use this word to a scientist, and I know the word no isn't always comfortable, but we know that these effects come through generations based on many factors. Is there something you've done or a study you've read that you find particularly insightful into that?

Dr. Frances Champagne

You know, I never like to overfit theories to any given study. So I'm really all about what does the colle the work collectively tell us about these phenomena? Because it's so easy to get excited about a specific finding. Specific findings are in a specific species or at a, you know, It's done in a specific way. So again, they're all building blocks. I would say when I'm trying to describe the importance of these inherited epigenetic or acquired epigenetic changes, I often use he Agouti mice as an example. And I think in large part because their whole coat color, their fur color completely changes color, right? So it is such a precise and salient way to describe what can be going on, right? So if mothers have a yellow fur color, their offspring will have a yellow fur color. But if you give those mothers a hot a diet that creates increased methylation during pregnancy, the coat color turns brown in their offspring. So it's a way to kind of show how these changes can be transmitted. And behavior is such a complex outcome that it's much more nuanced, I think, when we try to focus on behavior. So I love the Agouti work. The studies looking at the transmission of odor response during a stressful or traumatic experience and how that perpetuates across generations, I think is a really nice example because again, it tries to disentangle the effects of, you know, mothers and all these other things. So for me, those examples in animals really highlight that this is going on. And of course, there's been work showing that if you manipulate the germ cells directly, the epigenetics of the germ cells directly, that this can lead to changes in offspring. I think collectively that highlights this can happen. So now I think a lot of people are are kind of standing back and saying, okay, we know it can happen, but under what circumstances would it necessarily happen in kind of a real system, as opposed to when we control everything.

Amie Penny Sayler

When you mentioned the odor studies, can you talk about that study and what was discovered?

Dr. Frances Champagne

There was a study showing that if you paired a shock exposure with an odor, it would change the way that offspring and grand offspring would respond to that odor. So it's both a kind of a learning mechanism, right? So you've kind of paired this kind of shock in mice is is considered a one-trial learning. It's it's very salient and negative. So it's a way to kind of assess learning. And the fact that it was specific to a single odorant molecule, it's not like you've just changed your sense of smell, but it's really specific to that, suggests that there's some, there's this memory element to the transmission that that can have, you know, really profound consequences for subsequent generations. So I think that's, you know, one of the, I'd say best known in terms of kind of trauma uh and its long-term consequences. And again, I think it's strong because it tends to dissociate the different other routes through which which this might be explained.

Amie Penny Sayler

So to be clear, those those subsequent generations aren't experiencing the shock. They're just reacting to the odor.

Dr. Frances Champagne

Yes. And interesting. I think generally that's how these studies operate is that, okay, we want to see if an experience in one generation that does not occur in any subsequent generations can predict an outcome in those generations.

Amie Penny Sayler

So, you know, in humans, you do have often have father involvement, you've got different sides of the family coming together, you've got culture, you've got just world experiences outside of the family, you've got what's happening in the family. What do you do to try to study? Okay, let's translate some of this into what might be happening in humans. What is your work focused on with humans?

Dr. Frances Champagne

With humans, I avoid the question entirely and leave it to much braver people in the field. You know, the people who are doing this work best have access to multi-generational samples. So they're there, you know, studies that have been ongoing. You know, we've got studies that that started, you know, at the end of World War II or that are using archival data from famine records. But again, you can't you can't causally manipulate these things. You can't go around exposing people to trauma and seeing what happens. You can just try and work with populations where that's been well characterized. But my goal has been really to find out ways we can ask better questions, right? So we know that this can happen. Does it always happen? Really, what I think, and a lot of the field has done this as well, is try to take a step back and say, okay, we know this can persist multiple generations, but we don't really know what goes on from one generation to the next. So working back and thinking, okay, our hypothesis here is that the trauma or stress or whatever experience you want to explore in this one generation is affecting the next generation. How is it doing that? You know, what are the multiple routes through which that's happening? Once you understand that, then you can say, okay, then what is going on from this generation to the next? So I think there's a need to kind of really get in the weeds of how this is happening in a way that is able to integrate all those different pathways through which multi-generational effects can persist. So one thing we've been doing, for example, is asking the question well, if we think that stress, trauma is leading to epigenetic changes and that these are persisting, let's explore that. So, what is the effect of stress on your epigenome? You know, and how quickly does it change? And under what circumstances does it change? So we've been kind of trying to kind of work back and figure out, okay, how do we get from stress to epigenetics? How much stress, you know, does it matter how old you are? Does it matter, are there experiential variables that affect that?

Amie Penny Sayler

Well, and that's what's, you know, I think promising for us is that this is not set in stone. And because we as humans have so many variables around us, some of which are in our control, some of which are not, but this isn't uh, you know, your story is written and there's there's no changing anything about it, is kind of the encouraging part for humans. It's good information to have and to understand, because then we can figure out, well, what do we do with this?

Resilience and Positive Stress Responses

Dr. Frances Champagne

Yeah. I think that's certainly been a really important theme in the work because again, this is a system that's meant to be malleable, to be responsive. In terms of the science, I think there's been a lot of interest in establishing that this could persist for multiple generations. But under natural occurring, you know, naturally occurring experien um events, you would maybe not see it. And so why would that be? And when we look at, for example, cycles of abuse or stress transmission, it's very clear that the normative response is resilience, right? So it's not that this is dictating our biology, dictating the biology of our descendants. There's so much room for change. And there should be, right? So you if if stress occurs once or in a in a very acute way, sure we should be able to respond to that, but we shouldn't always be passing that on to generations unless it's useful for them.

Amie Penny Sayler

And I assume some of this kind of flips the other way too. We're looking at stress responses, but you can have sort of gifts or positive stress responses or experiences that, you know, kind of imprint the epigenome as, as it were.

Dr. Frances Champagne

Absolutely. And again, I think the focus tends to be in research tends to be on disease risk, right? So though I think that there is change in that. And and, you know, another way of thinking about this work is what promotes resilience? What promotes people to have really well adapted stress systems that can respond to stressors, because we need to do that, but also allow us to work and function well in the world that we live in.

Amie Penny Sayler

That sort of leads to my next question is what is most exciting to you that's sort of happening in your work or in the field right now that you're eagerly looking forward to the results?

Dr. Frances Champagne

Yeah. There's so much. I mean, it's, you know, the science that's going on is all so amazing. And there's these new tools to really get at the details of things. I tend to be a lot more big picture in thinking of like the things that interest me. You know, for for us right now, these interactions between prenatal and postnatal experiences in predicting long-term outcomes is exciting because, again, it's a general framework for thinking about how vulnerability or you know, resilience interacts with later life experiences. And that to me speaks in a more broad way about what goes on with humans, that we don't tend to just experience one thing and then there's nothing going on in our lives and we can use that. So, um, and you know, in thinking about endocrine disruptors, it's really hard to avoid uh endocrine disruptors. They're used in, you know, the modern world that we live in. It may not always be possible to eradicate those from biological systems. But if we know enough about how later life experiences can shape the pathways that are targeted by those prenatal effects, then we can intervene. We can figure out a way to lessen the biological impact of these other phases. So for me, that's really exciting. You know, I'd say generally the tools available for us to study epigenetics and the long-term effects of early life environments have really become enhanced over time. And I spent a lot of time working with animal models because really there was no possibility of studying these things in any kind of meaningful way in humans. But I would say that's not true anymore. There's a lot you can do with humans. You can look at dynamic changes in the epigenome and response to stress. You can get biological samples that are meaningful from parents and offspring, and even perhaps grand offspring, and start using some of the big data tools that we have now to truly try and understand the patterns over time. The premise that we can transmit more than just our DNA across generations is exciting to think about, right? It's this idea, and I think in large part it's exciting because it it speaks against the hypothesis that we are wiped clean, that there's there's no room for this baggage coming from grandma and grandpa. But the idea that there is something being transmitted. Now, how much of an influence it has on our biology and and uh is is certainly a question. And it certainly is malleable, so it's not, you know, you're it's not your destiny. But it's a it's fun to think about that. And you know, I think there's a lot of interest now in your biological history and you know, genetic history, thinking about what made you you. Um, so for me, that's really exciting. But to me, it's also even more exciting that in addition to that, there's all these other factors that are layering on that to shape who you are. And it I think it moves us away from thinking in in too narrow a way of what how we became who we are, and that we are really the product of some really amazing and interactive pathways.

Amie Penny Sayler

My dad recently passed, and so been missing him and thinking about mortality and all of that, not to get too out there, but when you're talking about the potential lasting effects that, you know, babe isn't coming into the world as a blank slate, there's something there from previous generations. It's an interesting philosophical question about, you know, okay, my dad is gone from this earth, but is he? Because I'm here, my children are here, you know, it's it's fascinating.

Resources and Contact Information

Dr. Frances Champagne

And when you look at ancestry DNA sites, you can now you can look at common ancestors from hundreds of years ago that you share with people. And it's you may not know them, but it's just fascinating to think that that some part of that individual is in you. And so I think it's true of DNA, and I think it's true of the environments we experience as well. Is there a way that listeners can follow your work or learn more about what you do? Yeah, I'm not a big social media user, but you know, I keep my website here at UT Austin up to date with some of the papers that we've we've been doing. So that's a great way to kind of see what what we've been working on, what we're thinking about. I really do love working with people who have questions that overlap with with what I'm interested in. And so I tend to ask these broad questions and work on a lot of different projects because I'm just, you know, everything's so fun and curious.

Amie Penny Sayler

Well, that's wonderful. Well, and we will link your website in the show notes. Awesome. Thank you so much for your time today, Doctor. Really appreciate it.

Dr. Frances Champagne

Thanks, Amie.

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Dr. Frances Champagne

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