On the Mic with Mike #1: Heart to heart with Dr. Katey Rayner

My name is Mike Strong. I'm the new President of CIHR, and today's our first episode of On the Mic with Mike. You wouldn't have heard about this yet – it's something brand new and what we're going to be doing is talking to investigators across Canada to try and get a bit of a sense of the excitement of their research, how they've gotten into their research field, and what they see for the future.

And today, we just happen to be here in Ottawa. As you can tell, it's the middle of winter (it's January) and we're going to go for a cup of coffee with Katey Rayner, who's one of our investigators from here. So why don't you join me and we'll have a chat with Katey.

Well, welcome, Katey!

Thank you!

So for those of you who don't know, this is Katey Rayner who's joining us today. Well, this is the first of a series that we're looking to do within CIHR. I call it "On the Mic with Mike."

And the idea is that we're having conversations around the country with investigators at all stages of their careers, in all different areas, to try and get a bit of a sense for why you're doing this.

We all know, we sit around a table and there's this level of excitement. We love what we're doing, right?

Right.

It gives us opportunities nobody else could do.

But that's us. And so how do we actually communicate that?

Right.

So that's what this is all about.

Right.

So thanks for joining me and taking time out of your day.

Yes, of course.

So, how did you get into this?

So, for me, it was not necessarily having a moment like a lot of people did – like where I was always a curious kid, staring at things under the microscope, or I always loved to take things apart and put them back together again, or anything like that. I don't think anybody would have said, looking back, that it was clear that she was going to become a scientist. I think I was always very interested in science and medicine. I identified, by the time I was in high school, I already knew that plants were less exciting to me, but the human body was very exciting, so science, not all of it, was very exciting to me.

But were there high school mentors, you think, that might have helped you along those lines?

No, it wasn't that. I think at the end of the day, it's really about when you're looking at the university catalogue and you're looking at what are your options, I think even now, we don't do a great job of really exposing children at that age to the true professions that are out there with respect to science. So for me, there was engineering, or there was science, or there was art...

Right.

… And it was only when I got to university that I started to get exposed to these – you realize that medical research is, in and of itself, a field. It's a path and it's a career. So that was when I started getting involved, was when I started to see these courses of learning about how diseases work, at the molecular level. I was in a program at the University of Toronto that was called Lab Medicine and Pathobiology and that was really the purpose – to teach not just biochemistry and memorize everything and spit it back out again, but really to take that knowledge and apply it to human disease and human function, and why these things work, and how.

Now, was that a full undergraduate program or it was one of the courses within it?

No, it was a full program and, actually, I was a guinea pig in that program! I was in the first year of it, and the idea was "Can we introduce this concept of medical/biomedical research to undergraduates?" So we tend to leave that to graduate school or medical school, when people have already largely decided a path to some extent. So the idea was to introduce it earlier and, many of us from that graduating class are actually researchers today, whether it be that we went to graduate school and then are in research, or we did medical school, then graduate school, and are in research, but many of us went that path.

Was there a time in the course of all of that when there's an "ah-ha" moment, there's something beyond this degree, there's an opportunity?

Certainly. When I learned that there was such a thing as a biomedical research lab where you could go and manipulate cells in a dish and ask whether or not a pathway was maybe contributing to a disease, that was just totally fascinating to me. The idea that we could do that with our hands….

And so I started as an undergraduate student after my second year of university, working in a cardiovascular lab. So that was the beginning of my cardiovascular path.

Okay.

And so that was the first realization – the fact that these diseases had research labs associated with them, it wasn't just a physician treating the disease that was fixing the problem, it was: "Why does it happen to begin with?" And so much of that we don't know. There's SO much we don't know.

So now, you're into cardiac research now.

And so you just mentioned that you have a cardiac lab that you've been partnering with?

Yes.

Just Brownian motion – kind of a random chance it worked out that way?

Yes. I think that most Canadian families deal with cardiovascular disease in some way. 30% of the Canadian population suffers from heart disease in some way, so we all are affected by it. So certainly I had family members who had cardiac issues, and then about halfway through my university, my mum was diagnosed with a myxoma on her heart – a benign tumour on one of her atria. So it was fine because she got surgery. There were no long-lasting effects, but no one knew how it happened. Nobody knew why. Is there a gene? Is it genetic? Do I have to worry about it? Should I get tested? What is it going to mean? We all, in the family reacted differently. I took a very pragmatic approach to it. You know, I felt like if we know the cause, do we have a test? What are we going to do? It was a moment where you go: "What do you mean you don't know how this happened?"

Right.

And then you step back and you realize there's so much that we don't know, especially with cardiovascular disease, which is so common. How do we not know how it really happens? I mean, we know the surface…

Right.

… but we really don't know. We really don't know why, you know, the 38-year old...

Yeah.

… everyone knows the stories, right: "But my neighbour, she bikes to work every single day. She's super healthy, and yet, she had a heart attack." And everybody knows a neighbour who's 95, smokes a pack a day, and is walking around, right?

Perfectly fine, yes.

So, if we knew it all, we would understand those people and we would know, but we don't. We really don't.

So if we look at that time, that period of time in your life when one is just full of curiosity, right?

Yeah.

So we've all been through it. We end up where we are. But then you have to make some really tough decisions, right, because the road to being a researcher is not a short one.

Right.

You know, it doesn't matter where you are in the world, we never find 100% of people being funded continuously.

So you are entering into a very competitive field. So was there a moment in the beginning of this pathway when you made the conscious decision and said, "You know, I do want to go down that pathway"? Can you remember that?

Yes, I definitely remember that in graduate school. So I was starting a Master's and I was already really interested enough to say: "Okay, I want to do my Master's in cardiovascular research and biochemistry." I was really unsure about whether or not I could do it. I looked around, like you say, and I saw all these people struggling, in some cases, to get their research funded. So I wasn't sure, but I knew I really, really liked it. So every time I thought of an alternative, it was "Well, no, I don't really want to do that." And then it becomes a "Well, I'm just going to try. I'm just going to have to go for it." And then it starts off at the beginning of your career, you apply for awards or you apply for scholarships, and they're really, really competitive, and if you don't get them, it can be really, really disheartening.

And then you may lose opportunities. You may not be able to go to the lab that you really wanted to go to, and do that project you really wanted to do. So I was fortunate, from the beginning, to be funded, and that made a big difference. Getting that scholarship as a PhD student made all the difference in my research, my confidence and, of course, my ability to financially do the research, and the ability to then continuously get funded. You know, you go to the next step, and you go to the next step.

So what could be the next step then? In particular, as we look at science nowadays and career paths, there's this concept that, yes, you're in an undergraduate or a graduate degree, whether you do a combined Master's, PhD or however it works, but then if you're going to continue down this pathway, you're going to be doing a post-doctorate, right?

And nowadays, and certainly in my time, and effectively yours as well too, that's about the time you start thinking about having families.

Right, yes.

And at some point, a little job security would be nice.

So one of the questions I get a lot is: "So how do you make that decision?"

Right.

So for you, how would you… because you went to Boston…

Yes.

So that's a big change.

Yes, absolutely. And New York City, even bigger.

Yes.

Yes.

So take us through that thinking.

Well, you're absolutely right, and I think that is probably the number one question I get as a female researcher from other women, is: "When do I have a family?" And you know what? I get it from men all the time as well. There are people, as you say, who are basically at a time when building a family is central to their mind and so is building their career, and somehow there's the impression that the two are not somehow compatible. So what it took for me was seeing that it can be done, of course, so I went to Boston first and then New York. So I went to the same lab, and we just physically moved from Boston to New York, so it was one position in two States.

Now, you were married at that point?

I was married at that point, but no children.

Alright.

And your husband, he's in the research world?

No, he came along with me. So that's another thing – there's the whole idea where people have spouses, partners, families. What do you do? Do you move them? Do you uproot people? I mean, that's a big thing that we overlook sometimes, when people are making career decisions.

Right.

So for me, my husband was able to say he'll put his career on hold and he was able to find work and do everything great in the U.S. as well, but not everyone can do that, right? So I was fortunate in that respect.
And then really, it all comes down to my postdoctoral mentor. So I knew her first by her name from her science. I had read all of her papers and followed all of her work in the cardiovascular field. Then I met her in person at a conference and it was right around when I was looking for that next step. Do I go and pursue the postdoctoral fellowship and do I make the leap? I met her, and she was very nice, obviously, and enthusiastic, and positive about the science, the work, the possibility. But then she received a call on her cellphone from her three-year old child and said: "Could you just hang on a minute? I've just got to take this call."

Really? Okay.

And I remember distinctly going: "Oh wow!"

It can be done.

It can be done. And there's lots of ways to do it. You can't naively think it can just get done like maybe other people can do it, but certainly it can be done and there are ways and tricks and things you can do. And that's basically what I did, was I then just learned from those around me who were doing it. The mentorship was so essential to that piece. Not only was she scientifically the best mentor anyone could have ever have (and she continues to mentor me regularly – mentors never go away). But also from a personal point of view, to see the way somebody builds their life professionally and personally and succeeds at both, then you can say, well, this is what could work for me and this is what may not work for me, and these are the things I can do. So mentorship is totally key to that.

So that raises an interesting question, right? Because certainly, I'm a tad bit older than you, but came from a period of time when if you were going to do science, the clinician scientist or PhD, one of you gave up life.

Right? You were going to be on weekends. You'll be working late at night, the rejection. You have 24 hours to get over it, right?

Yes.

And there was a certain bit of a lifestyle arrangement for those in there. And my sense has been that's really evolved, right?

And so when I talk to a lot of young people right now that are thinking about a research career, they remember that. They remember seeing, you know, the guys who were burnt out, or all the rest of them were just…

Yes.

… They don't recognize that there is this balance that can be struck over time.

And yet, once you're in the field, it's very difficult to stay with that balance because we're competing every day, right?

We're competing in our science, we're competing with...

… so how do you that? How do you maintain that balance and that competitive edge that keeps you as a very successful researcher? How do you do that?

Right. So I think the unifying theme, to answer that question, would be asking for help. So whether it be on the personal side from family, friends, neighbours, whatever it takes to manage your family life, but more importantly, on the research side, to actually ask for help. So that means, again back to mentors, so my postdoctoral mentor, Katherine Morris, continues to provide me help, but I have lots of mentors. I have people, professionally, that mentor me because I want to be in a more of a leadership position. So you pick their brains about this. You ask for their help. Obviously, my lab is an incredible resource for me. I depend of them. I ask them: "Guys, grant deadline is coming up. I really need everybody to just be all in, and let's help each other," and everyone is all in. So we're all helping each other. So it's not the solo person who has to stay late to finish their experiment because their project has to go to the next level. Everyone is there together. It's complete teamwork.

So that leads me to a question: Still at the bench?

So, a little bit. So I made the mistake once of telling my lab that I really like doing animal studies.

Yes.

So they wrote me in to all of the large animal experiments that we do. So we have lots of tissues, we do pre-clinical models. So that involves animal testing and things like that.

Right.

And that's a lot of data that we have to collect from multiple samples, multiple tissues, this kind of thing. So I'm in there with them for that and, to be honest, it's fun, because it's kind of this team event that we have. We joke that we compete, you know, who can take the cells fastest? Who can do all these things? And it's a lot of fun. So I do some of the work then, but, they really do it all. I'm just there to consult them and to really guide them, and really it's more about the questions they want to ask…

Right.

… and the data as they interpret it, as opposed to looking over their shoulders, to see if their hands are in the right spots or not.

I mean, that's what's really intriguing about this, right?

Yes.

Because I know when I came through my post-doctorate, we never talked about that.

Same as you, my supervisor was really my mentor…

Yes.

… for all my life, for all of it.

Yes.

But nobody ever sat down with me and said: "Mike, one day, you're going to have a lab."

Yes, right.

And that lab is not actually going to allow you to do any work.

Right.

They will finish it, and the techniques you're using are somewhat archaic.

Right!

Understood. But that phase of being a researcher, where you actually get to think about what is the question we're starting to tackle and how de we get people to help us get to that answer…

… And then it becomes a very broad community.

Right.

So as you've moved into that phase, you're not entirely – they still let you do some things, right?

Yes, right.

But you will get there.

And you know, that is actually by far the most fun part of the work, is actually thinking about the problem and thinking about what to do next. So sometimes, of course, it can be hard, but it's the most fun. So, actually, about two or three years after I started my lab, I felt like, for the first time, I was really, truly intellectually free to think about the biggest problems that we were facing in our experiments. And the reason for that is because, for example, as we know, obviously, CIHR funds all of our research, but we are constantly asking for funding for different things, and that can cause us to be a little bit disjointed in our thinking sometimes, because it's really that little pet project we really want to get funded or it's the continuation of that other one that we want to get funded. So sometimes our thinking can be disjointed. So when I was securing my funding, it was the first time I really said: "Okay, so what do we just want to do?"

Right.

What is the exciting question that needs to be answered? What is it?

Exciting questions, right?

All right. So, you know, obvious bias right here; I also do microRNA work.

Right.

And to me, there are many other RNA species that are worth looking at.

Right.

I mean, like a few little ones, right?

Right. Yes.

So what is it right now about your research that you find so absolutely exciting?

Am I right? So all of us could do what we call pillar one, right?

Right.

The sort of primary stuff coming into it.

Yes.

Oftentimes it's hard to explain to somebody why that is that so important to your mom's myxoma.

Right?

Right, yes.

So what's so exciting about it?

So I think what really gets me to go "Oh my God, are you kidding?" on a regular basis comes from the fact that we still surprisingly don't know what cells are actually present in a tissue. So we don't actually know, for example, the heart, what is the cellular composition of the heart? So that seems crazy, if you think about it.

In our world, I too do work on microRNAs. It's hard to explain to people the excitement between our understanding and our…

Yeah, right.

… But, inevitably, most people think RNA is something that's really straightforward.

Right.

That goes away.

Yeah.

But they can't see how that, which is really fundamental research into cellular biology, then ultimately has any meaning for us later on, at the disease state.

Right.

How do you grapple with that? How do you bring that conversation forward?

So one of the things that I always explain to people is that we don't know how things work, and I mean that in the most fundamental way. We don't know how – and microRNAs are a perfect example. They were discovered 10-15 years ago as a completely new thing. So it's like saying DNA was discovered. It's its own thing and the cells need it to – so people think genetics, they think "Okay, I know about genetics. They're passed on from parent to child, and so on." That controls the way that our body functions, but then things like microRNAs then control that and they control what your genes do. And we didn't even know they existed 10 years ago, let alone that they might actually be causing the disease.

Right.

So when you think about that, that's where I start. I say the thing about it is, your genes, as much as there might be excitement about CRISPR, and all this gene editing and cool stuff, ultimately, they're pretty static sometimes, at least in sequence. But what they do and how they function is not static at all. You can modify that so easily.

Right.

And one of the ways is actually through microRNAs. And the thing about it, part of why we know so much about microRNAs actually is because things to inhibit them, our blocking function, were made available and tested in preclinical models really early on. So that actually means that the technology is keeping pace with the discovery in terms of their ability to be modulated during disease.

But than can be a bit of challenge, right?

I mean, on the first, I think we both agree, RNA is far more important than DNA.

Right, yes.

Let's just cover that. We just lost half our audience, but that's alright.

Right.

And I agree with you. I mean, we are 10-15 years max in terms of the understanding of it.

And we seem to have come through this phase where everybody says, "I have discovered the microRNA du jour for X disease. We're now done." Right?

Yes.

And yet, for me, it seems that every time we do that, we're making a terrible mistake, because the complexity of the interaction is all regulatory.

And there are times, I know, when I sit in the lab, and I'm looking at this, thinking, at some time it has to end and we have the answer.

Right.

But in science that doesn't happen. So you're at a point in your career, particularly in the whole cardiac area, where this is just starting to bloom.

How do you deal with that uncertainty, that there might not be closure?

Yes, we had an example, actually, where we started working on a microRNA, and it got fairly advanced into the clinical application, meaning that a company was really interested, and they really wanted to apply into the clinic, but we didn't know enough about it yet, and it was only when we started to learn its complexity that we actually said, "Everybody, actually, it's not ready yet." So I think that the reality of the complexity is that it can sometimes be a barrier, because we know what happens if you jump in with two feet and you just use a drug because we think it worked in mice or whatever it is, and we just need to do it. So knowing – I think of the understanding of so much of what we do as a human chain, and we're all linked together. Not one of our discoveries necessarily is the one that led to the thing, but it's actually our understanding that we all drag the field forward. So sometimes your contribution may seem like it may just end or it may just be put into the atmosphere and you don't know where it goes, and you don't know where it's going to go. So now that we're learning more about – one of the coolest things, I think, is what cells make up tissue. So we think that in a heart it should be muscle cells, and of course it is. There's lots of muscle cells. They contract the heart, of course, but it's mostly endothelial cells in the heart. These are things we didn't know before, but technology is teaching us.

So that's assuming you're a first-time…

So why? Why is it cool?

… so it's two different cells, give me a break.

Right. Okay. So everybody now has assumed that after you have a heart attack, or if you have heart failure, it's because the muscle cells have died because of an event or an injury, and you have to repair the muscle cells. And of course that makes intuitive sense. You need your heart to contract. You should repair the muscle.

Right.

However, imagine if, in fact, the reason for the function of your heart not being up to par is actually because the endothelial cells (that have been not looked at) actually need to be repaired and they're the ones that actually have been lost.

Can't you just put new ones in? I mean, isn't somebody making them nowadays?

Yes, but the new ones they're making are cardiomyocytes. They're the muscle cells. They're not making new endothelial cells because we thought that the cells that were damaged were just the muscle cells. So what do we know, right? So now we've learned that stem cell therapies that are out there have some benefit to the heart, but not as much as everybody thought. People thought that for sure you could transplant a stem cell, it would regenerate into a new muscle cell, and the heart would get better. But it's just not working that well. Is it because we're pushing them towards a muscle and we should be pushing them towards something else? Maybe. Maybe we should be, like you say, throwing in endothelial cells and maybe things would get better. But until we knew that the cells were there, what they were, we would have no idea.

Same thing with arrhythmias. A lot of people have atrial fibrillation and electro-conduction problems with their heart. Turns out that the electrical conduction system of your heart is lined with immune cells. They didn't even know. People didn't even know there were immune cells there.

Right.

And they're actually communicating with the neurons that are causing the stimulation of the heart. So now step back, and you think, well, now that we know that there are immune cells all over the electrical conduction system, maybe it's immune therapy we need to give people when they have atrial fibrillation, not electrically shocking them and hoping to trick the heart to go back into rhythm. So this could actually completely flip the approach to therapy, if we just know the basics of what it is that we don't know. And I mean, those are just examples.

So now let's circle back to the beginning.

Yes.

Did you have any inkling that you'd be that excited about what you were doing when you were 18?

Yes, I think I've always been somebody who has been driven by curiosity – the "What do you mean?" And sometimes the frustration, to be honest. You see something and you ask "Why don't we know more about it?" For example, something that I see around me all the time and I deal with and other people deal with is mental health.

Right.

Why don't we know more about the pathologies that contribute to mental health? Why don't we know? Why don't we know the interactions? Why don't we know the biology? Why do people not get the right medicine? It's because we don't know. So things like that, you can see how that can really shape you into how you do either your research or your career or, in my case, both.

So I'm going to ask you some off-the-wall questions here.

Yes.

But things that always fascinate me. So imagine you go back in time, in science.

And this is like anywhere back where you want to go.

Who do you want to talk to?

Oh, that's a great question. The obvious choice for me is Rosalind Franklin. I want to know what it was like working with Watson and Crick. I want to know what happened? What were those meetings like? How did they go? What happened?

For those who don't know who she is, Watson and Crick, all right, but who is Rosalind? What did she do?

So Rosalind Franklin is the unsung hero discoverer of DNA. She was overlooked for her contributions to the structure of DNA. So this double helix, that structure that we all know and love – and that I have on my sweatshirts at home – she was not acknowledged for her contribution to this. So we all know that Watson and Crick were given a Nobel Prize. We know their names. The names are all over buildings but Rosalind Franklin wasn't, largely because she was a woman, and a lot of the belief in the way that the facts rolled out is that much of that structure came from her work, and they built on it. So that would be fascinating to me, to learn, compared to how we know now, how much things have changed – not all things, but a lot has changed. What was it like then to have that? What really happened? How did that go?

That would have been when, 50 years ago?

Yes, or more.

At least.

Yes.

And so labs at that point, they're still schooled in DNA, they didn't know what it was.

Yes, absolutely.

So would she have known what was coming down with that?

No, I think we often assume that sometimes the status quo, as things used to be, we often use it as somewhat of an excuse to forgive, to say "Well, that was how things were back then."

Right.

But most of the time, the people who weren't given a fair shake know perfectly well that they're not being given a fair shake. So I would say that even now, if I were to transport myself back in time to talk to her, there would still be very much an element of…

I think she knew perfectly well that there was an injustice. As I said, it can continue to happen now, it still happens.

So let me ask you a second question.

In your view, most important discovery, period?

Period? That's a tough one. I'm going to go with – it sounds uninteresting – but still microRNAs.

Okay.

I still think that the idea that an entire class of molecules in a cell remained completely obscure until really 15 years ago, is still shocking to me and amazing. And then that has, in the short term, answered a lot of questions.

Right.

I think in the long term it's going to answer even more as we learn more about how they actually do their job. How we currently think they do their job is rather narrow, but I do think that will change the way that we understand how cells communicate. The fact that these microRNAs are spat out by a cell and they get communicated to another cell and get taken up, and they function there...

That's even more recent though, right?

It's even more recent. So you think about all that stuff that we're building, I think we're going to look back at that discovery of these and maybe it's a point of also just non-coding RNA in general.

Right.

The idea that DNA = RNA = protein, that sort of dogma…

Right.

… has now been turned right back around. I think that is going to be a complete – it has been a game changer – but will continue to be even more so of a game changer.

My final question to you: so you've got a young family, right?

Do you talk about this at the dinner table? Do they know what you do?

Oh yes.

Yes? Okay.

Oh yes. In fact, my son was sick last week and (he's seven) and my daughter was asking me why he's sick. And I said, "Well, you know, we have little bugs that go around," and then she was very confused that bugs (she's four)…

Okay.

… and she said "Well, what do you mean?" And I said, "No, no, they're not bugs, they're like germs." And I explained. Well, we got right into it – What are immune cells? What do they do? How do you know if you're winning? How do you know if the germs are winning? I mean, we are right into it. They know what DNA is. They know what genes are. They think it's fascinating.

Right.

They think it's so interesting.

Do they come into the lab with you?

They have done, yes. They have done. Yeah, they certainly don't get that. And I've explained when you do an experiment. And sometimes my son would ask me "What did you do today?"

Right.

And I would say "Well, I wrote a grant, and I went to a meeting, and I took a conference call."

Yes.

I mean, those are not very exciting things. So he would say "Well, what did you discover today?"

Oh really? At seven?

Oh yeah. And he would do this even younger. So it would put me on the spot a lot.

Right.

Because I would say "Well, nothing." So I would find myself kind of explaining what the conference call was about. So I'd say, "Well, we have this research project where we want to look at someone's DNA and their cells, and we want to find out if it's causing the cells to die more than the other cells," and he would say "Oh my gosh, mommy, that's so cool." So then I started to just introduce the language to them about, as simple as possible. But yes, we talk about it all the time.

Great. So, Katey, I really appreciate having coffee with you and this chat!

Yeah, it was great!

I mean, we share a bit of research interest anyways…

Yes, absolutely, yes.

… but at the end of the day, this is very exciting stuff you're doing.

Great. Thank you.

Thank you very much.

Thanks a lot. It was lots of fun.

And good luck with things.

Thank you.

And maybe it will get you a grant!

Yeah, maybe. That would be nice!

Well, that's it for this first edition of "On the Mic with Mike." I do want to say thank you to everybody who's helped, and Katey for joining us here today. The name "On the Mic with Mike" – I have to say thanks to Colin Feore who actually came up with this name for us. So, Colin, thank you! And to all of you, we'll see you on future editions of this. Take care!