Baylor College of Medicine

The Epigenetics of Blood




Alice: Hi everyone. We're welcoming Dr. Margaret Goodell to our podcast today and we're really excited to have her. She's been a pioneer and a leader, in multiple fields, in research at Baylor. And without further ado, let's jump right into it. So Dr. Goodell, well, happy to have you on our show today, can you tell us a little bit more about yourself and how your research interests have evolved over time?

Dr. Goodell: Well, thanks for having me. It's really a pleasure to be here and talk to you and the broader audience that's out there. So I've been at Baylor for about 20 years and before that I did my Ph.D. in England and my postdoc in Boston. And even though I did my Ph.D. in England, I actually grew up in the Midwest and so I was able to move around a lot during my sort of upbringing and training in science. I started out in my Ph.D. actually being interested in stem cells. In those days, I was working on embryonic stem cells and I remember having to persuade my thesis committee why they were of any value, because nobody really had worked on them and nobody really knew very much about them. And I said, well, they have all this potential and you could use them to make a new mouse and all of this stuff, and they didn't really get it for a while. But then obviously it became very popular (embryonic stem cells did). And then I decided on my postdoc to work on hematopoietic stem cells and that really launched the line of investigation that I've been doing ever since.

So when I came to Baylor, I had the view of really studying the fundamental mechanisms that regulate hematopoietic stem cells, that really regenerate all of your blood cells continuously throughout life. And even then stem cells were not really a buzzword, they were something I thought had a lot of potential, I was interested in how things regenerate, and how it's essentially a program of development that is ongoing even when you're adults. So it's a special window into that developmental process, which I thought was very fascinating, but it wasn't a very popular field either in hematopoiesis or anything else. Although, there were pockets of people that were interested in regeneration of skin or liver or muscle. And so there were people that were interested in stem cells. But really it was a few discoveries about embryonic stem cells and induced pluripotential stem cells that galvanized the whole field, and really captured all of the work going on in stem cell biology that was going on at the time. And I was already maybe five years into my faculty position here when that really happened. So I got to really ride this wave of excitement in the field. So that was fortuitous. And I guess that's one of my lessons for the audience, which is that you have to choose something you're excited about and decide to work on it and be determined even if it's not really popular at that moment because you don't know, you know, it could be something that becomes really popular and you might be able to contribute to the growth of that field, which I feel that I did and my work did, and I also benefited from all the other external interest that was going on at the time. I guess I would say it was a lucky break that I was interested in that and then it all came to fruition because of a lot of other events that we're going on at the same time.

Snigdha: I was wondering if there was like anything in particular that sparked your interest and stuff?

Dr. Goodell: So I don't really recall a moment where I decided what was interesting about them. When I was doing my, when I was ending my Ph.D., it was the time of increasing interest in the concept of gene therapy, and gene therapy has obviously had its real ups and downs; and really the people who were interested in stem cells were from the gene therapy field because they viewed stem cells as the vehicle for it. Because if you could modify a stem cell then you could make any therapy more permanent. If you could re0implant them into the body. So my interest
was more basic and more fundamental, but I ended up going to a gene therapy lab as a postdoc because that was where you had to go if you wanted to study something like stem cells, that's how unpopular the field was at the time.

Snigdha: So the next question I wanted to ask was, did you have any role models or early influences in life that pushed you to go into science?

Dr. Goodell: I really didn't come from a scientific family or anything and you know there wasn't really anybody around me who was interested, but I think I showed early interest in it and I had a grandmother who was always sort of trying to identify things in us, in me and my sisters that we were interested in and would send us books. The days of books, you know, you could read a book when you were 7 years old or 10 years old, instead of going to the internet. And I think I really enjoyed that literature and it kind of got me hooked. And so by the time I was finishing high school I knew I wanted to do something in science. I didn't really know, I was interested in astrophysics, as well as biology and ended up going into biology. But it was kind of unformulated, just that I really enjoyed science. I think it was the inquiring nature of it, wanting to understand how things work.

So my undergraduate degree was kind of unusual. I started out as an undergraduate in a small liberal arts college in Connecticut and then I decided to do a semester abroad in England in London at Imperial College of Science and Technology. And the way that the British education system works, they put you into the extreme end of sort of research if you're in science very early on. And so when I got there, which would have been my junior year abroad or my first semester of my junior year abroad, I was actually starting to read scientific literature already; which, if I had been back at in Connecticut I still would have been reading textbooks. And so once I got into scientific literature and really started reading things in depth, I got super excited and then that summer I stayed for a year instead of a semester, and then I worked in a lab at summer and then basically have been working in the lab ever since.

So, for me what really cemented? It was not just reading science the way that we're taught it, you know, in undergraduate classes in college which I actually found kind of dry but it was understanding how it works. How research works from the laboratory perspective. Not just getting in the lab but really being able to read the papers and understanding how the discoveries went. What got me super excited, this seems like ancient literature to you guys, but I did a big section when I was in England on regulation of bacterial gene expression. And it's kind of a very simple system, it was like Lambda phage and how Lambda regulates its gene expression and how different bacterial genes are regulated. But it was just super exciting at the time and I read the whole series of literature about how these discoveries were made. And so for me, it was also kind of insight into how a series of studies lead to a greater understanding about a biological system. And so being able to put that all together, that was kind of the magic for me.

So that's a great question too. So I was finishing my postdoc and I started to go on the job market and I cast a wide net. I find when I'm trying to recruit people a lot of people have very clear preconceived notions about where they should go for their job, which as a general piece of advice, I think that's kind of a mistake because you really, there's not that many academic jobs in any given time, you really have to go where you're going to get the best opportunity, meaning a good starter package and a good environment, the combination of those two things. But I didn't have any preconceived notion having grown up in the Midwest, you know, having been trained partly on the East Coast, lived in England for a while. I sort of just was able to look at anything and when I looked at a number of places, it really helped me prioritize. What was going to be important in an environment. So I don't think I really had a good sense of what was going to make a good scientific environment at that time when I when I started looking for a job, but it was really through the process that I understood that better. And in the end it came down to two top choices. I had another fantastic offer from a place which I won't mention. But you would say is ranked extremely highly. And what it came down to for me, in fact that other place offered me a little bit more money, a little bit better start up package, etc., but I thought that the mentorship that I would get here at Baylor was, was going to be better. It was a gut feeling on the basis of the people that I would be working with and I think that was absolutely the right decision. I've never looked back, and even realizing that that was the right decision and the mentorship that I did get has allowed me to sort of use that as a guiding principle in my own behaviors going forward. So I try to be a great mentor. I try to recognize great mentors and really utilize those principles in my whole professional life.

Snigdha: So were there any particular challenges or obstacles you faced as a young scientist that influenced your career path? And if so, how are you able to overcome or adapt?

Dr. Goodell: You know there's always a lot of challenges. There's a lot of grant rejection, there's a lot of paper rejections. I actually just tweeted about this a couple of nights ago because I was counseling one of my students who got a grant, her training award rejected, brutally rejected, there was some not very nice comments on it. I just saw this is not necessary, sometimes reviewers are really just not very nice. On the other hand, I thought well this is a great training opportunity because this is really how it works in the real world and you have to be resilient.  And a lot of PIs we joke about this all the time that it does take a lot of resilience and being determined that this is what you really want to do, that you're doing the right science. I remember a grant that I had that I considered — the work that I'm doing now is still stem cell biology, but we started working on this one gene called DNMT3A. It's a DNA methyltransferase. And when we sort of stumbled upon this and really started working on it, I realized that it was super important and now I feel that it's probably some of my best scientific work, the whole body of work that has evolved from that discovery is really what I think is some of my finest work. But I could not get a grant on it. I submitted an R01 four times. And every time I was absolutely brutalized by the reviewers and they said, "oh, there's work that's premature", "it's not very clear that's supported" and etc. It took publications from other labs in the field to show that the work was, in fact, incredibly important. Again, this was another example of sort of a serendipity and being in the right place the right time and working on something before it became really popular. And all of a sudden this became one of the most popular genes in the field. And all of a sudden, I didn't have any trouble raising money for it anymore. So, it's, it seems kind of sad, but I knew that it was important. I knew that this was the right Gene to work on and that these were the right experiments to do. And so I was able to dig in and keep working on it. That whole discovery was really about 10 years ago. So really mid-career. But you know, you're still continuously having to overcome those kinds of challenges, I would say.

I would say it a completely different challenge, though, is in a way more interesting. Which is, what are you going to work on? And how does that evolve over time? And I've thought about that a lot because there have been other lines of research that I've been really excited about and then decided for one or another reason not to continue working on that because at any given time you only have so many resources. You only have so many people and you really just can't do everything. And so this DNMT3A project is a great example because we had just had a Nature paper in a different area of interferon signaling and its impact on stem cells that I realized was also really a great area. And I was determined to write another grant on that and keep working on that. But this DNMT3A project started happening and I just didn't have enough resources, people or money, to work on both of these big, big projects. So I sort of put all my chips onto this other thing. So, it's sort of made me realize that sometimes these choices are a little bit like gambling or playing cards, you know, it's the Kenny Rogers song, you gotta know when to hold 'em and know when to fold 'em and you have to make choices. They're not always going to be the right choices but you, you have to sort of put your chips on, you know, this particular hand that you've got at the moment. Or you have to say, well, I know this is cool work, but I can't get anybody else to think it's great, I can't get the paper published where I'd like it to be because these reviewers just don't get it, whatever, whatever. And, and then you just have to move on sometimes and work on something else and maybe that area will be more ripe another time. I think you really have to evolve as a scientist. You have to allow your work to evolve, you can't think "I'm going to work on the same protein for my whole life", unless it's a really fabulous protein. It's important to evolve but yet that decision is a hard decision every time you have to face it, right? Am I going to go in this new direction? Am I going to get funded in this new direction? Should I stick with what I know? And people know me for stem cells, they've known me for that forever, will I ever get funded for this? This DNA methylation thing? I don't know, but you have to, I guess, you have to have the courage of your convictions and be willing to be courageous and do something else. Even if that means to give up something else, it's also potentially very fruitful.

Erik: Actually can I ask a follow-up on that? Really, as a PI, a lot of what you're doing is sort of managing other people. Would you say that's a correct statement?

Dr. Goodell: Absolutely, and you're really not trained for that at all. You might have had an undergraduate working for you or something like that but you're not trained to run a team of 10 or 20 trainees and staff.

Erik: So I guess my question is, how did you learn how to manage? Where do you think you picked up the skills? Because you run a very successful lab, I mean, by every measure. So, I think that would be great for our listeners to hear because I think it's something everybody should be thinking about.

Dr. Goodell: I don't think I necessarily did a great job in the beginning and I didn't really have any courses or anything like that and there is a lot more emphasis now on training us to be good mentors. And I think that's a wonderful thing and hopefully all of you, when you're in the position, will take advantage of that. So how did I learn to do it? I learned from my other mentors. So I learned from the guy who hired me who was my chair, basically. I learned from looking, watching other labs either do things I didn't think were the right way to handle it, or were the right way to handle it. And I also realized that there was more help available than I realized at first. So, for example, when I did have personnel problems, there are people whose job it is at Baylor and all professional institutions to help you deal with problems; and they have strategies, they have other places to go to. I've done everything in my career, including you know, encouraging people that I knew to seek help for mental health concerns, you know? And I mean, that's something that isn't really discussed. But there are great resources for that. People might have had other issues going on. And so once you kind of get into it, you realize that even if you don't feel like you're a good manager, that there's a lot of help to be found if you seek it. So, that's one thing. And then I guess the other thing is again, kind of returning to first principle – it sounds kind of silly, it's like that Kindergarten book, right? It comes down to treating people the way that you would want to be treated yourself. And once you really incorporate that into your philosophy, I think it makes a lot of difference. And even when you get frustrated with people, you have to think, well, I'm frustrated, maybe they're not working hard enough in the lab or whatever. But why is that, is there something going on with their life that they're not telling me? Maybe their grandmother died or maybe they really don't like the project and this isn't the right lab for them. Maybe the technician needs a different kind of a job because she's just not motivated in science anymore and yet she hasn't figured that out. So once you really put that as your sort of guiding principle – that you really have to treat everybody as you would want to be treated, that's your North Star. And I think that has helped me be a good mentor both in my lab and in dealing with some people now that I'm a chair of a department, I feel the same way.

Erik: Well, thank you, I think that's great for people to hear something.

Alice: Our last question that we were hoping that you could answer, is a little bit more science- heavy. How does your knowledge, our knowledge of how stem cells differentiate, how do you foresee that impacting the future of patient care?

Dr. Goodell: That's a great question, the stem cell field definitely exploded because of the promise of stem cells for various kinds of therapy and I still think we're getting there. It is taking a long time and it will continue to take a lot longer, but I think the impact is many-fold. From a very basic science perspective, understanding the mechanisms of how stem cells differentiate has given us insights into other things. So, for example, in cancer, because many cancers are fundamentally – at least cancers of the blood, hematologic cancers – are thought to be a combination of both a block in differentiation as well as something that drives those cells to proliferate inappropriately. And that you really have to have both of these sides going on at the same time in order to cause a leukemia. And so this gene that I studied now, DNMT3A, that's really important and its major role is to permit efficient differentiation of stem cells and so it seemed to be really an interesting gene for regulating stem cells. But once we discovered that it was also important in cancer because it's frequently mutated in cancer, that gave us really fundamental insights. Now it turns out it's a tumor suppressor so it's not very easy just to kind of fix it to cure your cancer. But, nonetheless, it's given us a lot of insight into how these particular malignancies arise and to think about how one could effect that change with drugs or other approaches for cancer treatment. So, yes, one point is that stem cell research can help in areas outside of just regenerative medicine, because it's giving insight into normal development and also cancer. In terms of regeneration I do think we are getting closer to, let's say, the long-term goal of tissue replacement in certain circumstances and there are better and better protocols for taking embryonic stem cells and differentiating them down towards specific lineages. Lots of work in neuroscience to do that and you can get fairly pure cultures of certain neurogenic lineages. It's kind of hard to just implant them by injecting them into a brain right now but we might really get to that point where you could use some of these cells and sort of patch a tissue in a way. So it's still a process but there's a lot of research in the field, a lot of excitement and I think we're getting there, there really will be a great tool. Stem cells will be, in general, a great tool for regenerative medicine and for therapeutic purposes.

Alice: I think it's really fascinating. Actually, I'm not so familiar with the history of stem cell therapy and stem cell research, but I believe it has been decades since the discovery of differentiation from fibroblasts. Is that correct? And since then, can you describe some of the progress that the field has made and what are some of the biggest challenges to bringing it to patient care?

Dr. Goodell: So I would say there's a few times in your scientific career where you'll see something come along that shocks you as an investigator. You're reading this paper and it's like "oh my gosh I can't ever imagine that that happened" and IPS cells were one of those. PCR was one of those revolutions, absolutely revolutionizing things. In fact it was kind of thing where people thought "well, that's so obvious, I should have thought of it myself" when PCR was developed but nobody had. And obviously it really transformed everything you do. And I think CRISPR is another example of something that most of us could never have envisioned, and it comes along and just like wildfire just transforms virtually everything that all of us are doing in the lab all the time. So IPS cells was like that for the stem cell field for sure. But in the very beginning, they were virtually impossible to harness. People didn't really understand how they were made. Could you make them from any cell? Could you make it from an adult skin cell, a skin cell from a baby? Could you make it from a hepatocyte, a blood cell? People were just sort of trying everything. They were then trying different genes. Well, you know, these four genes could do it, but could you use a micro RNA or could you use a combination of three genes in a drug? And then really what is this the process, is it an epigenetic process that resets it. And does it really reset it back to completely normal or only partly normal? So, all of these questions were really the focus I would say in the first 5, 6, almost 10 years really trying to understand how that works. And now the field is really maturing and focused more on, OK, now let's make something really productive out of them. Can we not only make a cardiomyocyte, but what does that cardiomyocyte do in terms of its normal function? Mostly still, when you differentiate embryonic stem cells, you get something that resembles a differentiated cell that would come out of a newborn or even a fetus. So it's not really something that you can use to replace in an adult because actually the function of those cells is a little bit different so people are still trying to overcome that gap, how far can you take them. But it's evolving all the time.

One of the other really exciting developments in the field was realizing that under certain conditions you could put embryonic stem cells and a few other things in the media and you could actually get these self-organizing bodies, something that looks like a little eye that you can develop completely artificially, these eye cups.

Erik: I had a question if there's time, I want to respect your time, but I had a tag-along question about your research. So DNMT3A. So obviously I've already shown, I'm not an expert on it, but I was just wondering if I'm understanding it correctly, if you could expand on it because I think it's really cool. So it basically helps in stabilizing – it's only in the nucleosome. Is that correct? First off?

Dr. Goodell: It's in the nucleus and what it does is it puts DNA methylation all over your DNA. And DNA methylation is just a mark that helps regulate the gene expression. And what it does is it puts it in very specific places and we still don't really understand how it knows where to go and when to go. And if you don't have it there, the way that we think about it is that the methylation in general, as a very broad brush stroke, is important for shutting down the expression of genes. So a very simple way to think of the purpose of this DNMT3A protein is that it's very high in the stem cell. And then as soon as the stem cells is told to differentiate, it has to go and shut down the stem cell program, and if you don't shut down the stem cell program, you can sort of get a little bit of differentiation. So, it'll start to go down that let's say the red blood cell lineage and make red blood cells. But it still thinks that it's kind of a stem cell and it gets confused. And then that's probably why if you don't have DNMT3A those cells are then more easily transformed down a malignant lineage because they're trying to be something, but they're also thinking that they are a stem cell that continues to proliferate.

Erik: Okay. Okay. And so was I understanding correctly that it also is thought to maybe have some function in like the phase of DNA within the nucleus? I think that's what I was starting to read about that I thought was really interesting, and maybe that's how people are thinking it might be affecting expression levels as well and whatnot?

Dr. Goodell: That is possible. We do think that, so, one of the papers that we published recently, we showed that there are large regions in the genome that have little or no DNA methylation. So, I would say that, first of all, almost all your DNA has a ton of DNA methylation it's just covered with it as a mark, okay? Just like peanut butter on your bread, whatever. It's just like all over it. And yet there are these little pockets that don't have very much methylation and those are important regulatory sites and DNMT3A is definitely important for changing that state. So making sure that there's the peanut butter over all those little holes. But what we found, this is another example, actually, of sort of following the research, even though it's not strictly related – we started looking at DNA methylation in general. Where is it in the genome? What is it doing? How is it regulating things? So, in a way it's a little bit tangential to what DNMT3A specifically is doing, is asking what DNA methylation is doing. So, when we looked really closely we saw not just these tiny pockets that lacked DNA methylation but large tracts of DNA that lacked it. And I'm talking about 10 KB or 20 KB which are really large chunks of the genome that don't have DNA methylation that, before our paper, nobody knew that these large tracts existed. That paper was a few years ago. And so, then we thought, well what are these large tracts for? We call them canyons because they're like Grand Canyons, like really big and they have a little river in them, there's always a gene in them. So it's kind of a nice analogy and so we kept thinking hat are they doing? What are they doing? And we think those canyons are there for a number of reasons, but in our recent paper, we showed that they are sites of 3D chromatin interactions. And that several of these can be interacting together. Sort of like the center of a flower that these pieces of DNA are all coming together and sort of locking together around these big tracts of low methylation. And we suggested it might be a phase transition type of event that's also got polycomb proteins and other things involved in it. That was our observation and that's an area I would love to go into in the future as well.

Erik: No, I think that's amazing. I think that's a really novel and cool way of thinking about it. When I was reading I was like well, that makes a lot of sense when you think about it, kind of manipulating the phase like that to be regulatory. But I guess you're not even speculating about regulation, but are you? I don't know.

Dr. Goodell: We do, we actually think – so those canyons exist in two states and I'll give you another one of my crazy analogies in a second, but the canyons exist either in an off state or in an on state, and the ones that are involved in these really long-distance, 3D genome interactions, which are megabases apart – so it's like multiple megabases, which is also like a scale that wasn't envisioned before – it's the canyons that are involved in those really long-distance interactions are the ones that are in the off state and not the ones that are in the on state and it's not random. So, it does seem, I'll give you my other analogy of these canyons and what DNA methylation might be doing. Again I was thinking a lot about DNA methylation as a mark and how important is it and it's even interesting to think about where it came to be evolutionarily and how it's used in different organisms and things like that. And when I really thought about these canyons, what I kind of realized is that the genes that are in these canyons – I mentioned that there's like a river in them – and if you look at what those genes are, they're always the most important genes in the genome. There's a gene called PAX6 which is critical for eye development. If you knock out PAX6, you won't get any eyes. Okay, so PAX6 is one, it has its own special, little canyon. It's just sitting there all alone, protected in this big void of DNA methylation. Almost all the Hox genes, which are involved in embryonic development, have their own little canyon. Many other transcription factors that are really important regulators have their own canyon. So I was really realizing these are all really special things. And in fact when you want to turn on one of those important genes, you turn it on like gangbusters, right? Everything gets turned on and all the transcription factors are landing there at once. And they're turning it on and then later, it has to be turned off.

So I was probably on one of my flights – now we're not flying anymore, because COVID – but I started thinking of these canyons. When they're on they're like the busiest airport on the planet. So it's like JFK Airport in New York, or our Houston airport is a pretty busy airport too, or O'Hare in Chicago used to be the busiest airport, and when it's daylight time that is the busiest airport. But when the Earth rotates and that's out of the sun there's not very many plans are landing in Chicago O'Hare anymore at 3 o'clock in the morning, right? Really not very many and so that airport is shut down. So I started thinking about these canyons as sort of permitting, basically, the runways and that the methylation around it is the structure that allows that runway to have the lights  bright on when the planes are landing and the lights off when they're not landing. And so it's kind of the infrastructure around it. It might not be the landing pad itself, but these are structures in the genome that are really allowing everything to be landing at once when it needs to be on, you know, everything is going. But when needs to be off, everything is off. And it's sort of a big structure, that only the biggest airports, the biggest cities, the most important cities are allowed to have one of those special canyons of special genes.

Alice: I'm really tempted to ask this question now. I think we have a tiny bit of more time, so I'm going to ask two subparts in the same question. One, are there any other regulators that behave, as far as, you know, like DNMT3A. And two, have you guys considered looking at any other lineages besides hematopoietic stem cells.

Dr. Goodell: Great questions. So there's no other gene that really acts exactly like DNMT3A, that is so special for – at least in the hematopoietic lineage – for the stem cell and has such a clean function. However, there are other genes that have semi-overlapping behaviors, and so one of them called TET2 and its purpose is to remove the DNA methylation that DNMT3A and other proteins put down. So it's interesting, it's the opposite side of the coin and when you knock it out it has a overlapping phenotype to DNMT3A. So it has a similar role in cancer and it has a related role in regulating stem cells too, even though it kind of has the opposite molecular or biochemical function. It removes methylation instead of putting it on, it has a similar outcome in terms of what it does for the stem cells.

Alice: So as you were mentioning, it's a regulator for a lot of different important genes in different lineages. So I was wondering, is there a potential, do you think, for it to be heavily involved in many processes throughout the body?

Dr. Goodell: So we know that it's also involved in differentiation of embryonic stem cells. In fact that's one of the places its role in differentiation was first discovered, and we have suspected that it plays a role in some other lineages. But that hasn't been looked at that carefully for a number of reasons. There is evidence from some other labs that it may play a role in skin differentiation as well. It certainly may play some other roles but that's another area that would be worth looking at in more detail.

Snigdha: It was really great to hear from you about your research and I really love your analogy – the flower one, and the airport one, those ones will probably stick for a while. But yeah, it's really exciting to hear about your research and your career path. Did you have any final words of advice for students who are looking to start their own research years?

Dr. Goodell: I would say research is really fun and it's forever varied and that's really one of the privileges of working in this area. During the pandemic shut down that we're in right now, some readers may be listening to this in the future and not be in that any longer. But that's where, you know, we're recording this in the middle of our pandemic. I think a lot of people have asked whether they're happy in their jobs, whether this is something that they really want to be doing long-term. I feel we're very fortunate, in research, the pandemic has actually pointed out exactly how important research is and has offered many new opportunities for really great questions that should be addressed outside of stem cell biology as well. I think as a career it offers a lot of flexibility, it offers constant change, you always have new people coming in your lab, you always have new people to work with. There's always new exciting ideas. You're able to evolve your research, you're running your own little business. It's your own little business. And as long as you can continue to raise money for it, you can keep producing your products and your products are your papers that you sell to the community and you try to get the journals to publish. So it's very satisfying in that sense, as a career. Also, I have three children and I've had to manage that through being a PI. I started my family after I had been a professor here for a couple of years, and now my oldest is at college. So it also offers a lot of flexibility and I think that's great and research, you know, it's not really a 9 to 5 job. Unfortunately, it's like an all-time job. I'm always thinking about it. I'm often on my email at strange times the day and night, but it also means that I don't have to be in at 8:00 a.m. every day and I have flexibility. And that has helped manage having a family and that flexibility has been nice, you know, during the COVID era and things like that. So I would say it's really a privilege. It's a great career and it's a lot of fun if you don't get too down when you have the few setbacks that you have, you just have to keep plowing forward.

Snigdha: It's really awesome to hear from you. We really appreciate you taking the time out of your busy schedule. You know, you have a lot going on especially right now during the pandemic. But again, thank you so much. It was amazing to be able to interview you for this.  

Dr. Goodell: Well thank you all for having me. You had great questions and it's a fun opportunity to talk about some of these things that I think about, don't really talk about very often.