Episode 53: Laurel Hiatt on What’s Even Happening In Your Colon

Micrograph of a stain of a portion of secum removed during a colonoscopy.

Image: “Intermediate magnification micrograph of a sessile serrated adenoma, abbreviated SSA, from the cecum removed during a colonoscopy. H&E stain.” (Source: Wikimedia Commons)

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Transcript

Charles 0:21
Hello and welcome to Assigned Scientist at Bachelor’s. I’m Charles and I’m an entomologist.

Tessa 0:26
And I’m Tessa and I’m an astrobiologist.

Charles 0:28
And today as our guests, we have Laurel Hiatt. Laurel is an MD-PhD student at the University of Utah currently in the second year of their PhD. They study tissue specific somatic mosaicism, with the colon as their current organ of choice. Outside of the lab, they DM for all-queer tables of Dungeons and Dragons and hang out with their two dogs. Laurel, welcome to the show.

Laurel 0:48
Hey, thanks for having me.

Charles 0:50
It’s tremendous to have you. Uh, to, well, to begin with, we like to ask people, How did you get interested in science?

Laurel 0:57
Oh, I wanted to be a sci fi writer. I read like all of Michael Crichton’s work, and I thought he wasn’t a very good writer. And I thought that I could do better. But I figured I needed some basic level of scientific writing in order to take on that challenge. So I got really involved in science stuff in middle school, and then ended up really falling in love with it. I actually applied to my undergrad as intended psychology and Women’s Studies major, and then ended up doing like genetics and biochemistry research.

Charles 1:31
So was your first science love psychology, or did you sort of cycle through different disciplines?

Laurel 1:37
Oh, I’ve always been a genetics person, I would say, from high school, I guess that was the thing that really grabbed me. I think my interest in psychology was largely from like a social justice advocacy perspective. But when it comes down to like, what I like… I have a college professor who refers to the duct tape keeping the human genome together, because it’s an incredibly fragile, yet functional thing. And that has just always really appealed to me. And so I think I have an appreciation for, you know, biology and anatomy. And I mean, I’m, I’m half intended physician, so I like human health quite a bit. But I think genetics is the thing that has always sort of stuck with me. And now I’m getting a PhD in it. So I guess I’m sort of decided.

Charles 2:32
Well, if we take what I would consider a, not a shining star in the Sci Fi canon, but the Marvel Cinematic Universe, apparently, you could just go on and keep getting PhDs.

Laurel 2:44
Right? My partner likes to bring that up to me to upset me, where he’s like, how many prelim exams do you think you’re gonna do in your life? And I’m like, just…

Tessa 2:54
I mean…

Laurel 2:54
Just the one qualifying exam, I think I’m okay.

Tessa 2:57
My wife already has a doctorate and starting on her second, like this fall, so it’s a thing.

Laurel 3:03
Good for her, but I don’t I, I say as a hypocrite who’s doing an MD PhD program, I don’t have the stamina.

Charles 3:12
My best friend is actually planning on doing an MD PhD. And when they told me, I was like, why would you do that to yourself?

Laurel 3:19
It’s a good question. It’s a very…

Charles 3:22
I mean, I guess the answer to it is to be both a practical clinician and to continue doing research, right?

Laurel 3:30
Yes, yes, I actually was yesterday, talking to a MD PhD student who’s a few years ahead of me in the program, how basically, the idea is sort of that for a lot of folks, or at least the motivation to get into it is that you don’t want to be like, either separately, you want to be some juxtaposition of both. So a researcher who knows the clinical significance and path of their work, and a physician who was involved in research and evidence based, you know, standard of care, following the latest and greatest and like, I just, I have a terrible time choosing. So here I am.

Charles 4:12
Fair enough. So do you have a particularly pronounced passion for the colon? Or is it kind of what you’re just working on?

Laurel 4:21
It’s just, it’s sort of what I’m, I’m working on. I mean, I have an appreciation for it, I would say, I never expected to be in as close proximity to human feces, of different people as I am now. But I was actually… first I was originally going to be in a neuro anatomy lab for my PhD. And circumstances changed. I really liked the brain, but I’m interested in somatic mosaicism, and across different tissues and the brain space for that is a little bit crowded, for lack of a better word. There’s an official brain somatic mosaicism network that does super awesome research. And so the idea was like, Okay, what is an organ system that’s not the brain that I ,as a bold and intrepid, you know, PhD student can pursue? And the colon is kind of fascinating to me because it’s a very, it’s pretty simple. It’s a tube that goes through your body and it, you know, absorbs water and moves poop, and then it has some of the highest disease incidence globally in multiple methodologies.

Charles 5:32
I have three things that I want to say.

Laurel 5:34
Okay.

Charles 5:35
The first is, I want to make an extremely niche comparison that will serve an audience of maybe two people, because one of the entomologist that we’ve had on the show does work with ants. So the – looking at somatic mosaicism in the body, you… is kind of like looking at the field of opportunities to do taxonomic work in insects, and it seems like the brain is like choosing to go into ants, and the colon is more like choosing to go into like, various undersung members of Polyneoptera.

Laurel 6:14
That feels right. I don’t know the ins and outs of entomology…

Charles 6:21
That was just that one was just for ole Charles. And so then the second, the second thing is I, what you just said opens up, I think two great questions. One is a, I don’t think somatic mosaicism is a concept that most people are familiar with, so definitely want to go into that. And then also your statement on incidence of disease in the colon. So first of all, could you explain somatic mosaicism?

Laurel 6:48
One of my favorite things, I always say if I wasn’t doing this, I’d be doing like linguistics work. So like I quite literally, the breakdown of the word I think is helpful, were so somatic Soma refers to all the tissues in the body that are non germline. So basically not sperm, not eggs. So your somatic tissues, your skin, your organs, your eyeballs, all that good stuff. And the reason why that’s significant is because mutations that arise in the germline are going to be inherited by offspring, and, you know, perpetuate phenotypes and possible disease risk, whereas mutations that arise in the soma or somatic tissues aren’t going to be inherited. So they can be a lot more difficult to discover. But they aren’t going to cause you some problems, probably, I think the most common iteration of like somatic disease that people know of is cancer.

Cancer is a disease of, you know, somatic mutations accumulating. And that kind of leads into mosaicism, which is the idea that we as people are mosaics, we are, you know, billions of cells all hanging out together, sometimes cooperatively and sometimes not. And those cells accumulate different mutations at different times. And so I’m really interested in that at a tissue level. So why is weird stuff happening in my liver and not in my spleen, that kind of thing. And so the idea being once you put all the cells together, instead of having a single genome, we have a mosaic of different genomes of different mutations all throughout our body. And somehow, we persist as some kind of an individual. There’s also a lot of bacteria in there. Oh, yeah. Yeah, I respect lots of respect to those guys. They do make my life a little more difficult, since a lot of them hang out in the colon, and we have to make sure that we’re letting them do their thing and doing our thing.

Charles 8:37
I think the maybe the best clarifying question next is, well… so what?

Laurel 8:46
Yeah, so I am interested as a future physician, right in the development of disease, and especially in the prevention of awful things through screening and surveillance. And so going back to the column about like disease incidence in the colon, so like, colorectal cancer is the third most common cancer in the US and the second, most lethal, I know, other fun statistics, like there’s a there was a recent demographic incident that 4.3% of individuals will be diagnosed with colorectal cancer in their lifetime. It’s oftentimes thought of as the disease of aging, because your colon cells turnover grow forever, and you know, can accumulate damage. And so the so what I think is, if we can figure out what’s happening in our cells, we can catch them before they cause us problems. And maybe we can figure out ways to change their course or divert their energies, instead of coming cancers or I’m also really interested in inflammatory bowel disease, which has a lot of controversy, I guess as to is it genetic, is it environmental, etc, and it’s certainly environmental in some capacity but there’s some thought process that there might be a somatic role as well.

Charles 10:05
Yeah. Well, then, well, then the question, why is mosaicism important in this context?

Laurel 10:13
Yeah. So the idea being that if it’s hereditary, that’s really, that’s easy to, I mean, that’s not kind that people who study hereditary diseases and whatnot, know, it’s, it’s much easier to take someone’s blood, you know, look at a aggregated genome and say, Okay, you have – I think the most common example, people are familiar with his, you know, BRCA- So, you look for a BRCA mutation, you know, if you find one, that person is at a really elevated risk for breast cancer, you act accordingly. For issues of, you know, somatic mutations, and spontaneous diseases, which is comprises the majority of colorectal cancer and most cancers, actually, you can’t do that, you know, you can’t test someone’s blood and find out what’s going going on in their colon, if it’s only going on in their colon.

And so the idea of my thesis work, and a lot of various projects and various organ systems, I think is, okay, how do we figure out what’s happening in just our organ or just our tissue, and figure out the best thing to do clinically, or therapeutically, or if we should just watch and wait without, you know, I cannot remove the colon from a person and give it back later. And so that…

Charles 11:38
Not yet.

Laurel 11:38
Yeah, yeah, not yet. I mean, honestly, I’m pro that, like, we can make me obsolete if we want and just do that. That’d be great. But unfortunately, I’m not. I’m not confident in that in happening in the next, you know, little bit.

Charles 11:55
Yeah. Well, I mean, it would be great if that happened, but although on the other hand, um, I think it sounds really weird to have an organ taken out.

Laurel 12:07
Oh, can I interject with like, a sort of, I think it’s funny story, where I so I work with cadavers, you know, I am taking out entire organs, which is a really funny start to the story. It’s absolutely yours. But the funny part is, I have told my brother in my friend group about, like, the research, I’m doing that were taking out these organs and processing the tissues. And at some point, it came up that we are going to, you know, process a donor for the organs. And the is, basically this procedures got delayed by a few hours. And my brother messages me, and it’s like, oh, it was like the person just laying there. And I was like, Yeah, I mean, I guess. And he was like, oh, like, are they? So they’re just like laying there with like, their chest open? And I’m like, No, I’m not sure what your point is. And it came out that my brother thought that we were taking, like, live human beings and just taking out, you know, fun organs, like the entire colon, and the testes, and just and the pancreas and just removing those from random people just for funsies. And just sending those people out afterwards on their day.

Charles 13:21
Well testes, that’s…

Laurel 13:23
That’s fine. That’s…

Charles 13:24
I mean, well, that’s not invasive.

Laurel 13:26
That’s not invasive, for sure. But um, I they, I don’t know if the average person would want their entire colon removed just for research purposes.

Charles 13:37
Probably not.

Laurel 13:39
I mean, my, my medical understanding as a non surgeon, and someone who probably will never be a surgeon is like, we can take out parts of things pretty easy for taking out the whole organs. It’s not very nice of us for, uh…

Charles 13:51
There are no surgeons here to defend themselves, say whenever you want.

Laurel 13:57
I have to be careful because I work with some wonderful surgeons and I maintain my like non surgical bias of like, it’s not what I would do with my life.

Charles 14:08
Okay, well, so then, sort of the idea behind your research is that we can we can test people for certain for the presence or absence of certain alleles of different genes. And if they have them, then they are highly elevated risk of certain cancers, for instance, BRCA related to breast cancer. So that is part of some screening, but then for other organ systems, like the digestive tract, and specifically the colon, the disease incidence… they have a high incidence of disease, but a low…

Laurel 14:43
Hereditary component

Charles 14:45
Hereditary aspect. And so just doing sort of a standard genetic screening doesn’t actually help you that much in determining people’s risk of, say, developing colon cancer. So then the Um, concept of somatic mosaicism, in that these mutations can arise in colon cells at any point, and therefore…

Laurel 15:11
Yeah, yeah, sorry, I’m listening, and I’m nodding my head, which you obviously can’t see. But yeah, the idea being if we can figure out basically patterns in healthy cells versus cells that are on their road to no good, you know, maybe during a routine colonoscopy, you can take some samples, and instead of currently, basically, colonoscopy is just looking for polyps, you know, and we’re like, Okay, well, let’s take that out. Or if, you know, we find a polyp, let’s check back again, sooner than later. The idea here is sort of, okay, I can have a person get a colonoscopy, I can take a few different healthy tissue samples, I can do some kind of really targeted sequencing to look at specific genes. And I can say, okay, come back in five years, or 10 years, or 15 years or 30 years, probably not 30 years. That’s a little reckless. But you could have more…

Charles 16:04
Probably dead thirty years from now, who knows?

Laurel 16:06
Right? Yeah, live your life. Have fun. But yeah, where basically, the idea is sort of to get a better handle of people’s specific disease risk in a timely fashion while still being not invasive and not, you know, carving out in organ.

Charles 16:24
Yeah, I completely forgot about colonoscopies. And I was really sitting here wondering, but how would you get cells… but there’s a, there’s a convenient entry door.

Laurel 16:36
Yeah, I’ve developed a pretty strong love of the colonoscopy as a colon researcher, where I didn’t think about that much before. And now I’m like, You mean, people are already going in and scraping out bits of colon for me? Like, you mean, there are doctors out there who are doing the work for me, that’s incredible.

Tessa 16:53
You’re probably the only person we’ve ever had in our podcast, who has expressed a love for the colonoscopy.

Laurel 16:59
Listen, you know,

Charles 17:01
To be fair, nobody has expressed a hatred of the colonoscopy either.

Tessa 17:06
This is true.

Laurel 17:06
The needles are one direction, it seems like it’s the right one,

Charles 17:10
We have an n of one on opinions on colonoscopy at all.

Laurel 17:14
Yeah, well, it’s it’s sort of funny in the time that I was basically developing my proposal, because I basically, I one of the things that’s really fun and terrifying about being a computational Lab, which is what I’m in is that my PI was basically like, find a project and go do it. Because we don’t have a wet lab component, you know, and code is code.

Charles 17:33
Actually, let’s take a screeching on the brakes.

Laurel 17:37
Screeching the brakes.

Charles 17:38
I think just… I don’t actually know the demographics of our listeners.

Laurel 17:42
Oh, yeah.

Charles 17:43
But I know, there’s at least one guy who listens sometimes, who probably is not familiar with like, just the, the, the casual jargon of science. Well, just to lay it out. So PI is…?

Laurel 17:56
Oh, Principal Investigator. Yeah. Not a private investigator, not someone who’s following people around, but someone who is my boss, but also sort of my mentor.

Charles 18:07
To be fair, both kinds of PIs are kind of doing detective work.

Laurel 18:11
Oh, definitely.

Charles 18:13
Yeah. And then a dry lab, wet lab?

Laurel 18:16
Yes. So wet lab being I think what most people think of that? Well, that’s, I guess it depends. But what I think a lot of non science people think about when they think about science, so they’re like, you know, pipetting and test tubes. And, and I did in undergrad, I started out doing wet lab research for about three and a half years, did many a western blot, which is a kind of protein blot. And when I first started, I broke the case and you’re supposed to put it in and I cried, my PI let me go home. And I think about describes my relationship with wet lab research.

And so then you get to dry Labs, which can cover a lot of things. I mean, I think that… I did public health research for a couple years, which is like phone calls and surveys, which has its own, you know, Avenue. And then now I do computational work in my, like, direct lab where I tip tap on my computer. And we’re partnered with other researchers, where I help out with organ processing, and whatnot. But my lab itself – my PI is a former computer programmer in the industry, who then went into academia later on, so he gave me free rein to kind of find a project which is awesome, but terrifying. And I came up with a lot of really terrible ideas, I think before he came up with one that sort of work, but in that in that process, my mom actually had a colonoscopy and they found a polyp and it was just really interesting – for her to be going through it on like the the person side who was like this is the worst thing ever. And me to be doing it on the researcher side of like that, thanks for getting a colonoscopy. Glad we found the polyp, you know, but yeah, I understand they’re not they’re not beloved in the general community, perhaps, but I appreciate them. I think they do most of the time when they’re supposed to,

Charles 20:14
How did we get to colonoscopy?

Laurel 20:16
Oh, you were asking me about testing. And I was actually going to say that something I’ve spent a lot of time thinking about like, Okay. What do you actually do if I, you know, find stuff and colonoscopies are the, the obvious answer, there’s also the idea, there’s, like, fecal DNA tests, or basically you can test for, you know, if there’s enough sloughing of colon cells that might be, you know, present in the feces, which is less than ideal, and has not been as successful to my knowledge in like, clinical diagnostics, but I hold to colonoscopies as when people assessing my research are like, Well, what, what would this actually be good for? I’m like, Well, you could implement targeted screening in colonoscopy is basically immediately, which is a very eminent kind of sci fi technology, as opposed to the many years out would be, you know, take the colon out entirely, give it a wash and look at it, and then put it back in.

Charles 21:22
Yeah. So what is the… what is a, like, week in the life look like?

Laurel 21:28
It’s pretty glamorous, I gotta say.

Charles 21:33
Sounds like it.

Laurel 21:33
No. So I, like I said, I am in a computational lab. So a lot of what we do is working on the analytical pipeline of basically, the world of genomics is sort of intertwined with the world of big data, and you have this perpetual question of, okay, I have a few million or a billion data points. And I don’t know, if you have seen that comic of like data versus evidence and they like, or if someone draws, like a unicorn connecting the dots, you know, like, you can basically see whatever you want to see, when you have that much information. It’s about differentiate… differentiating, I think, what is usually called, you know, signal from noise. And so a lot of what I do is run code, write code, talk to other people in my lab who write code and feel like I’m sort of battling my computer at times.

And then there’s this other flip side, which is the processing of the organs where, basically, we get a call – we’re partnered with Donor Connect – which is a rapid autopsy nonprofit in Utah, where basically someone has died, and it’s kind of a time rush to basically get the organs in a timely fashion. And, you know, then I go in, and I hold a scalpel, and I slice and dice and I was trained by a surgeon who is awesome. And I, it’s super enjoyable, actually, to get to work with my hands in a more, you know, non screen context. And I also work on a really cool team of people who are studying other organs and tissues. So like, my, my best friend in my lab studies fertility and so he’s the reason why we take out the testes. And so we work together. And I appreciate having someone else who is willing to hold a colon as we get all the feces out of it, because I don’t think many people would do that for their friend. And he is committed to do it many, many times.

So I think yeah, I my life is nice for, like I said, I don’t like to decide. And I’m a MD PhD student. So it’s a good mix of like PhD research in the, you know, in silica space on my computer, actual organs, which is somewhat clinical. And then the, in the next few months, hopefully, I will be consenting patients to get colonoscopy biopsies, and that will be additionally very clinical and medical, so.

Charles 24:22
What happens to the rest of the body once you get all the relevant organs out?

Laurel 24:28
So we basically have an arrangement where we can only take organs that aren’t going to be donated for organ transplant. So that’s one aspect where before, you know, they take out the research organs they take out anything that you know, is going to help a person, which is great. And then they take out the rest of the organs and then I believe that the bodies are usually cremated and then returned to the families who consented to organ donation for both other individuals and science. So that’s the general process.

I don’t really, I don’t go into the surgical suites. I could if I wanted, but I would do a lot of standing. And there’s kind of this joke about med students where like your, your primary role in the surgical suite is just to be in the way, and I don’t feel the need to do that any more than I have to. But yeah, it’s it’s, I’ve actually been speaking with different people who are researchers involved in autopsy for research. And it’s like a very small but devoted field, which has been kind of fascinating. And I, and honestly, to go back to the Sci Fi thing, I sort of it, it’s something I really appreciate were one of the aspects of sci fi love the most was like Orson Scott Card, where they had the planet, basically, where the lifecycle includes sort of the death of like, the piggies, and they became trees, and they were really confused by how humans didn’t utilize their dead for the benefit of the community. And I believe there’s a quote, I’m probably butchering, but something to the effect that they say like, “so your dead in no way serve your living.”

And I just I really appreciate, you know, the the families who are willing to participate in, you know, the research process, because, in turn, I’m really hoping to be able to help people, you know, in the future. And so I think it’s one of those things that I forget how morbid it can be to people who are not involved that I spend a lot of time waiting for people to die. But I think that there is this community based element, I guess, of individuals living and dying and then contributing so that other people can you know, live better and, and die later healthier?

Charles 26:54
Yeah. I Yeah. I mean, I, listen, we’re all about death on this podcast.

Laurel 27:02
Great.

Charles 27:05
Thinking about it, I, so they don’t. So colon, is colon transplantation just not something that happens?

Laurel 27:12
Not, not really. I mean, they’re just… when you think about, Well, who would need a colon transplant, I guess, most people will have part of their if they’re having their intestines, from their own body removed, usually, it’s more so the small intestine, and if they’re having their colon removed, usually it’s only part of the intestine, I’m trying to think I met one person who had the entirety of their colon removed and had to be on a special diet. But that’s generally… it’s pretty uncommon. And the issue, I think, with colon transplantation is there’s a lot of low cell turnover. And the whole idea of you know, immunosuppression, because the body is fighting itself, you still want the organ to cooperate with you, and I’m not sure it could transplant and colon would really do that very nicely the way that a heart or kidney might, so.

Charles 28:02
Well, I guess it is a big tube.

Laurel 28:06
It is a big tube.

Charles 28:07
And you could probably cut out part of the tube and then it’s still a tube.

Laurel 28:13
Yes, that is generally my understanding how that…

Charles 28:17
I have a master’s degree. Um, well, so you referenced this earlier – why is there so much cell turnover in the colon specifically?

Laurel 28:26
Oh, so it’s like an assembly line where basically the colon has these crypts, which are kind of test tube shaped, but tiny that are involved in the absorption. So they form these little tubes, and they suck up the water. And basically, those are exposed to a lot, a lot of mechanical damage, a lot of exposures from what we eat, etc. And so they’ve got stem cells at the bottom that are constantly proliferating, and then they kind of go through up to the crypt and eventually get slapped up at the top. And so they basically they it is a machine that keeps running and replicating, so that everything can keep going as planned, kind of like the skin, you know, your skin, I think that’s probably the more useful way to explain is like, if your skin wasn’t turning over, you’d probably be having a pretty bad time considering everything your skin comes into contact with. Your colon is experiencing that on the outside and the inside, and every crypt turns over about every three days, which I tried to explain to someone and they’re like, well, three days isn’t that fast, and I’m like, what would you? What do you think about like a neuron taking like 20 years to regenerate?

Tessa 29:43
Yeah, I was about to say – even, even skin cells don’t turn over that quickly, I don’t think

Laurel 29:49
Yeah. It’s wild to me. And, and it’s something where like, when I think about it in my brain, it feels like a conveyor belt going at like 200 miles an hour. And it’s one of those things where I think That’s part of the reason why I find the field just really, of somatic mosaicism, like really interesting is you’re gonna have a completely different time looking at the colon than then, you know, the brain where a lot of things that people look at are happening in development, or the heart basically doesn’t regenerate at all, which is a problem when you have heart damage, but you know, as a result, heart cancers are pretty rare. And so like every tissue has its own puzzle with its own set of rules.

Charles 30:27
So then, is this rate of regeneration directly linked to the high incidence of diseases associated with the colon?

Laurel 30:35
Yes. That… someone might get mad at me for saying that definitively. Because it’s like a very accepted theory. But I’m like, yeah, like, most definitely. Where basically anything, you know, that has to replicate itself significantly more is going to have more hiccups and mess ups. And yeah, you know,

Charles 31:00
I mean, I guess intuitively that makes sense. Where if cancer is developing out of random mutation, the more opportunities for random mutation you have, the more likely it is to develop.

Laurel 31:12
Yeah, exactly.

Charles 31:14
All right. So what are the like, the directions of your research right now?

Laurel 31:18
So like I mentioned, we’re trying to get colonoscopy stuff off the ground. COVID made a lot of patient based stuff, super, super difficult. And then, in terms of using, you know, cadavers, and colon base, I’m really interested in, I call it regional, somatic mosaicism. So basically, colorectal cancer and inflammatory bowel disease look different along like, the length of the colon, like the right side, and the left side have completely different outcomes, oftentimes, treatments, presentations, etc. And so I am looking at..

Charles 32:00
Well let’s… why?

Laurel 32:00
That’s the question, right? Like, it is one of those things that is sort of funny in research where it’s like, everybody knows, and, and then it’s like, well, why? And it’s like, well, I don’t know, it could be a lot of things. Who can say? And I would like to say personally, and so there’s been theories again, that like, is it environmental? Is it somehow like, anatomically based? I’m wondering if it’s something that arises in development, like early on, because the right side of the colon derives from a structure known as the mid gut and the left side derives from a structure known as the hind gut, and they basically do different funky things in development.

And I’m wondering if there’s some way that those changes that happen, you know, in organogenesis or in the development of organs, when you’re, you know, in the in the fetus somehow set the stage for decades later, the domino effect of different mutations arising, I don’t know. But there’s this kind of really interesting method of analysis, it’s called, they’re called mutational signatures, and I have been trying for about six months now to figure out how to explain these in like a cool, fun, sexy way. And it’s really difficult because it’s sort of complicated. But basically, the idea is, instead of looking at the specific mutations themselves, you can look at all the mutations together and see what patterns there are. And you can tie those patterns back to specific mutagenic processes. Like there’s a signature that relates to alcohol that’s like found in the esophagus, there’s a signature that’s just associated with cell proliferation that’s found in basically every tissue, there’s a signature associated with like E. coli that you can find.

So basically, in looking at different mutations across the length of the colon and extracting the signatures, and then kind of making a lineage of cells and mutations, the way that you might make a phylogeny in evolution. My hope is to figure out sort of what’s happening, when and where, and then look at that, that in the healthy colon and then look at that, and the diseased colon and say, okay, at what point can we, you know, point a finger at this and be like, this is about to be bad. I don’t know if that makes sense with regards to a direction. But I saw I hold a really gross measuring tape up to colons, and I, and I take samples at different lengths. And then I hope and I pray that my pipeline will tell me cool things.

Tessa 34:35
I’m glad you mentioned a measuring tape because it would not have occurred to me how you might have measured these otherwise, like literally, it’s not even thinking about that.

Laurel 34:43
Yeah, I donated my own measuring tape, which looking back is like such a me thing to do where I could have just ordered one and had the lab buy it, but I was like, this is my project and this is my measuring… this is my measuring tape I’ve had for years, and I give this part of me to this project.

Charles 35:01
To… the people are donating their organs and you are donating an external organ, of the measuring tape.

Laurel 35:10
A tool that I have carried with me across, you know, states and whatnot.

Charles 35:15
Absolutely. In a colonoscopy – first of all, how would you get a like, scientifically useful number of cells?

Laurel 35:25
Oh, yeah. So the crypts themselves have an average of about 2000 cells. And so that’s the functional absorptive unit I mentioned earlier. And there’s about 100 crypts per square millimeter, I believe. And so the idea being there’s a lot of cells in a very small amount of area, and if you can take them across different regions, there’s a lot to go on. Now, the question with colonoscopy is, is it’s much easier to get the exact location and you have to process those random samples are often taken in colonoscopies anyways. And because the basically the epithelium or the surface of the colon isn’t innervated, it doesn’t actually cause pain in patients who are already getting colonoscopy isn’t having random biopsies, it’s not considered additional risk to take additional samples. So then the question of how many samples do I need? is a fun question. I have lost many a night of sleep over, but the hope is the research I’m doing and cadavers where I have the entire colon to look at will sort of inform how many I need to take from colonoscopies. But um, it’s definitely a question in, in progress. And once again, I appreciate my PI, my boss, because he is a phenomenal mentor, and gives me all the space to be like, Hmm, that’s an interesting problem, what do you think? which is a great way to fret and stress over the answers to these questions. But it’s, it’s been a, it’s yeah, it’s, it’s been, it’s in progress. And so the answer to your question is, i don’t know, we’re gonna find out.

Charles 37:08
Fair enough. So there are different parts of the colon, right? There’s the like, the big one, and then the side one, and then the sigmoid colon, which is right in front of the rectum.

Laurel 37:18
Yeah. So there Yeah, the… what we consider the ascending colon, transverse colon, descending colon, sigmoid colon, rectum.

Charles 37:25
[jokingly] Well, if you wanna be official about it.

Laurel 37:26
[laughs] Yeah, sorry. So, those are the main parts. Yeah.

Charles 37:31
So most of the colon doesn’t like feel pain.

Laurel 37:34
The, yeah, the epithelium? Like the top like the part of the tube that’s touching the inner tube is, yeah. And it’s one of those things where I think I want to be careful, because then if someone’s like, Well, I had a colonoscopy, and it was painful. I don’t want to be like, No, it wasn’t. But the anatomy of it is such that the the top part where they’re just kind of scraping, it’s kind of like, I guess, if you have enough, you scratch the top of your arm could probably slough off some stuff. So a little deeper than that, but it’s not deep enough where you’re hitting nerves. That makes any sense?

[quietly] I’m just touching my arm…

Tessa 38:10
Yeah, yeah. No, I know, I know what you’re saying. Yeah.

Charles 38:17
Do you have anything else that you would like to say on your research [that] we haven’t gotten to?

Laurel 38:24
I like what I do. And I think it’s fun, as someone who has listened to the podcast and heard a lot of people talk about their specific thing, to talk about my specific thing, where I think probably, there’s this funny cohort of people in like my department who sort of feel sorry for me, because they think that my, my PI told me to work with the colon, and and then they find out that like, No, this is my own project that I chose, and I’m just like, you know, what, I just really, really want to look at the colon in deciles. And compare this like, very specific data thing across the colon, like, that is my little specific hill, I have set my flag and I am going forth.

Charles 39:08
Somebody’s got to do it!

Laurel 39:09
Somebody’s got to do it. Somebody’s got to do it.

Tessa 39:12
What would you say would be like the outcome from your research that you’re most hoping for, you know, what would be the ideal outcome for your research?

Laurel 39:21
I want a like a very feasible gene panel and pipeline, that a person, like a clinician can press a button – not press a button, I mean, it’s more involved in that – but can implement in a clinic and it will help people you know, avoid the progression of disease without their knowing because like early intervention is everything. And so I think the goal is, maybe impossible goal is to have like, here’s… here are the genes to look at here are the things to look at. We have really incredible recent, like sequencing technologies for the past few years that make remarkable things possible. Like, can we help people avoid pain and suffering and money and, you know, mortality? That’s sort of the ambitious big picture.

Charles 40:12
Yeah, that is kind of an interesting point where like a lot of what you’re working on now, wouldn’t, maybe wouldn’t have you even been possible 10 years ago,

Laurel 40:20
Absolutely not. Like canonically not, where even just… I use, which is a whole nother thing. But I, we use a technology known as duplex sequencing, which is, like the last eight years, basically came into existence and has been, in the past few years, optimized to the point where it’s feasible to do what we’re doing. Like it’s one of those things where, like I said, the questions of like, okay, why, why is the right and left colon different have been around for for decades, but it’s really only now that there are a lot of both biological and like computational tools to sort of do what I’m doing, I feel excited to have stepped into the party at the right time.

Charles 41:00
So once you graduate with your MD PhD, what would a week in the life look like then?

Laurel 41:07
Oh, ideally, I would have more money. Eight years of… eight plus years of being a grad student is a little a little hard on the wants, but the hope is to do a… some version of a residency that has a research component. So there’s like, PS TPS, which are physician scientist training programs that are basically residencies that include research and I really want to be a medical geneticist is the current plan, you know, basically keep working in genetics, but work on the more clinical diagnostic side of things. And so I will basically be involved in research, probably 80% of the time, and then have like, a day a week where I get to work with people as their physician and, you know, be someone they hopefully trust and who treats them well. I mean, I think that’s the dream. Besides having money, or just slightly more money than I have now.

Charles 42:08
Well then the other question, do you plan… Are you, are you, are you devoted to colons? Or are you open to sort of organ polyamory?

Laurel 42:18
I am very open to organ polyamory. I think the colon has been a trustworthy organ system, I think that the colon has a lot going for it and would recommend to any of my friends. But I think that one of the things that’s kind of exciting about research, right, is it… it is constantly in response to itself, right? And so I have no idea what I would be working on in 20 years in genetics, and I think that’s part of the fun, you know, and so I think if I, if I, if I truly fall in love with the colon in the next few years, I would consider gastroenterology, but right now, I think I I love the genomes more than I love the cells in the colon they’re coming from.

Charles 43:07
Any other flirty organ systems caught your eye?

Laurel 43:10
So I have toyed with the liver, we had a bit of a tryst. I mean, the liver is actually my favorite organ. I think the liver is underappreciated.

Tessa 43:23
It regenerates.

Laurel 43:24
Yeah, it regenerates. It gets very little appreciation. It is the reason why, you know, people talk about detox diet. And I’m like, No, you just gotta love on your liver. You know. So I’ve thought about the liver a lot. Like I said, the brain maintains a… brain is maybe a little bit the one that got away. But that’s alright, I plan to have a long career.

Charles 43:47
Listen, between the three of us, right? The brain is a little bit overplayed.

Laurel 43:52
It is a bit overplayed it is and…

Charles 43:55
No offense to my best friend who wants to do brain research.

Laurel 43:59
You know, the brain gets a lot of attention. And I think some of that is warranted and some of that isn’t. And I myself recognize I am part of the problem. But yeah, I think the plan right now is just to see what the future holds when I finally graduate, you know, 107 years from now and have fun with it.

Charles 44:23
Well, I think that is a great place to move into the final section of the podcast.

Laurel 44:30
The end game.

Charles 44:31
Yes. Did I sent you a list of questions?

Laurel 44:34
You did.

Charles 44:35
Okay. Is there one that you would like to answer?

Laurel 44:38
Oh, so I’m a I’m a big horror person. I love horror a lot. And so the the body horror question, which if any parasites would you be a willing host for wonderful, I love I mean, especially with a colon right where I’m like, we have a super symbiotic sweet deal going on with bacteria. And so it’s like the next level of like, Okay, what about parasite. And to be honest, I, I don’t know, because on the one hand my feeling is they’re a little hurt, I think, that a parasite would be in my body and not contribute. That doesn’t feel like a healthy relationship to have. Yeah, but on the other hand, hear me out, what are those, like brain parasites that like make the like the ants do weird things where I’m like if I had a parasite who was committed to making me, like better about cooking and going for walks, like maybe, like..

Charles 45:42
Well, Cordyceps does kill you if you’re an ant. I don’t think Cordyceps kills humans.

Tessa 45:50
Yeah, yeah,

Laurel 45:51
I’m trying to figure out what kind of parasites I’m thinking of like alien parasites, anything’s on the table.

Tessa 45:57
Toxoplasma gondii is someone that goes after mammals.

Laurel 46:00
Oh, yeah. The know about that. People think about it with kitty litter, but it’s more so meat related? Yeah, I don’t think I want that one. It’s one of those things where in the in the human as the clinician sense as someone who I started my infectious disease unit three days before the COVID pandemic started in med school, I… am not very fond of parasites and bacteria and viruses.

Charles 46:27
Yeah, I do want to say one thing. I want to say one thing about toxoplasmosis.

Laurel 46:32
Okay.

Charles 46:33
I think, from what I can tell, the evidence that it actually like, controls your brain to like love cats and want to be near cats. is not really there robustly. But also… [cat meows loudly] Alan sounding off – if there were a parasite in my brain, and its only purpose was to be like, love cats.

Laurel 46:55
Yeah.

Charles 46:56
Love cats, love cats. I would… like, it would make… Yes. I have no problem with that. When people come in, they’re like, “you only love cats because toxoplasmosis” – I don’t care.

Laurel 47:08
Yeah, it’s a good time. Yeah, I mean, that’s, I don’t know, that’s a lot of things in your body that you do, because, I mean, you get into the whole the nihilism of endorphins and oxytocin and loving other people or whatever. But I’m like, if a parasite wants to give me like, crocheting as a hobby, who am I to say no. So I feel like a parasite who, like adds a feat or quirk is is will be reasonably welcomed into my my household.

Tessa 47:38
Although I feel like at this point, we could end up in a semantic argument about what what qualifies a parasite and what is like a symbiotic or, you know, a mutualist?

Laurel 47:48
Oh, yeah. Yes. And I think that’s probably a thing to think about, too, with the question where a lot of the things I thought about I was like, well, that’s not a parasite, it’s just a thing that’s hanging out with me. So I guess my kind of disappointing answer is probably no parasites I’ve heard of would I be a willing host, but…

Charles 48:10
The other thing is, I think you’re maybe – because you’re not an entomologist – you’re leaving a lot of great options on off the table.

Laurel 48:18
Yeah.

Charles 48:19
Because there are superficial infestations, and then they like hatch out of your body. So for example, a lot of like, anytime you get a bunch of entomologists together, in my experience, you get at least one person talking about the time that they got a bot fly, and then let it hatch out of them.

Laurel 48:38
Oh, how fun.

Charles 48:40
So that’s an option.

Laurel 48:42
You know, I guess I would consider that. I don’t, I don’t think it’d be something I would, you know, skip towards with excitement. But I guess there are worse things than to contribute to the lifecycle of another organism.

Charles 48:54
I’m on the fence about it, because on one hand, I do love bot flies. I think they’re really cute. They’re just like, so… have you seen a bot fly?

Laurel 49:02
I think so. It doesn’t come to mind immediately.

Charles 49:04
Well look it up later. I would say if you’re not squeamish, but like you handle colons, so I think you’re okay.

Laurel 49:10
Yeah, I talked about sort of, like, I’m very good at what I do, because it takes a lot. And by a lot, I mean, I haven’t found it yet, the thing that unsettles me.

Charles 49:20
There you go. And so there’s so just there’s so like, there’s so round, they’re so perfectly round, and the adults don’t even have mouthparts. So they just got this like spherical head. They’re very, they’re really cute flies.

Laurel 49:33
Okay.

Charles 49:35
So like on one hand, I love them, I would love to have that story. I would love to get those photos – hello!

Laurel 49:41
Right.

Charles 49:41
On the other hand, stuff under my skin really freaks me out.

Laurel 49:45
Well, and it’s one of those things where I’m thinking of like the long term I’m like, what if I want to get a tattoo there? And like now I’ve got like a like the skin. I don’t know how what kind of scar it leaves like…

Charles 49:56
I think it heals over pretty well.

Laurel 49:58
It heals pretty well?

Charles 49:58
Yeah.

Laurel 50:00
Okay, so that’s, that’s like a short show.

Charles 50:02
Also, what cooler tattoo could you get?

Laurel 50:05
You’re right.

Charles 50:05
Than like a bot fly on the place where you had a bot fly?

Laurel 50:09
You’re right. You’re right.

Charles 50:11
So now you have an even better tattoo option.

Laurel 50:15
You know what? Okay, that’s the parasite for the tattoo option and the tattoo option exclusively.

Charles 50:21
That’s the, that’s the Gay Agenda.

Laurel 50:24
That’s the gay agenda right there.

Charles 50:25
We found it. Well, I don’t… I feel like that’s an episode of a podcast.

Laurel, you’ve been a tremendous guest. Thank you for coming on.

Laurel 50:40
Thanks for having me.

Charles 50:41
If people would like to find out more about you or about your research, where should they look?

Laurel 50:45
Oh, so I have a Twitter. It’s just my name, Laurel Hiatt. I’m gonna be real with you. I mainly tweet about my dogs and trans jokes, but I do occasionally reference being a grad student and have results will be forthcoming on my Twitter. And beyond that, my, my PI is actually more science-y his name’s Aaron Quinlan, and he retweets nice things about me and my research so but you should follow me because I’m funny probably not for this. Yeah, other than that, I think keeping an eye on colon somatic mosaicism papers, because it is not a very, there’s not a lot of elbows in that room, so you’ll find me.

Charles 51:29
Wonderful. Well, I am on Twitter @cockroacharles, and Tessa?

Tessa 51:34
And I am on Twitter @spacermase or on my website, tessafisher.com

Charles 51:41
If you liked the show, or you think other people might like the show, please tell them about it because supposedly, a word of mouth is the number one way that podcasts grow.

Tessa 51:50
And until next time, keep on science-ing.

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