Hello Friends 👋

Dr. Steve McElroy, a neonatologist and physician scientist, discusses his research on injury and repair mechanisms in the immature intestine, specifically focusing on necrotizing enterocolitis (NEC) and spontaneous intestinal perforation in premature infants. He shares his journey from initially not wanting to pursue science to becoming a physician scientist, and how mentorship played a crucial role in his career. Dr. McElroy also talks about his pioneering work on Paneth cells and the Paneth cell ablation NEC model. He highlights the importance of listening, asking questions, and being open to new research directions. Finally, he discusses the impact of his leadership role as a division chief on his research and mentorship activities. He emphasizes the importance of mentorship, celebrating small victories, and persisting through challenges. Dr. McElroy also shares insights into his current research on chorioamnionitis and its impact on neonatal health. He highlights the need for creative think time and the value of understanding mechanisms in basic science. The conversation concludes with a discussion on building a supportive and fun lab environment.

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The articles covered on today’s episode of the podcast can be found here 👇

Paneth-cell-disruption-induced necrotizing enterocolitis in mice requires live bacteria and occurs independently of TLR4 signaling.

White JR, Gong H, Pope B, Schlievert P, McElroy SJ.Dis Model Mech. 2017 Jun 1;10(6):727-736. doi: 10.1242/dmm.028589. Epub 2017 Apr 27.PMID: 28450472 Free PMC article.

A direct comparison of mouse and human intestinal development using epithelial gene expression patterns.

Stanford AH, Gong H, Noonan M, Lewis AN, Gong Q, Lanik WE, Hsieh JJ, Lueschow SR, Frey MR, Good M, McElroy SJ.Pediatr Res. 2020 Jul;88(1):66-76. doi: 10.1038/s41390-019-0472-y. Epub 2019 Jun 26.PMID: 31242501 Free PMC article.

Lipopolysaccharide-induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood.

Fricke EM, Elgin TG, Gong H, Reese J, Gibson-Corley KN, Weiss RM, Zimmerman K, Bowdler NC, Kalantera KM, Mills DA, Underwood MA, McElroy SJ.Am J Reprod Immunol. 2018 May;79(5):e12816. doi: 10.1111/aji.12816. Epub 2018 Jan 25.PMID: 29369434 Free PMC article.

Host defense peptides human β defensin 2 and LL-37 ameliorate murine necrotizing enterocolitis.

Lueschow-Guijosa SR, Stanford AH, Berger JN, Gong H, Boly TJ, Jensen BAH, Nordkild P, Leegwater AJ, Wehkamp J, Underwood MA, McElroy SJ.iScience. 2024 May 15;27(6):109993. doi: 10.1016/j.isci.2024.109993. eCollection 2024 Jun 21.PMID: 38846005 Free PMC article.

Fetal exposure to maternal inflammation interrupts murine intestinal development and increases susceptibility to neonatal intestinal injury.

Elgin TG, Fricke EM, Gong H, Reese J, Mills DA, Kalantera KM, Underwood MA, McElroy SJ.Dis Model Mech. 2019 Oct 21;12(10):dmm040808. doi: 10.1242/dmm.040808.PMID: 31537532 Free PMC article.

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The transcript of today's episode can be found below 👇

Misty Good (00:01.232)

Hi, and welcome back to At the Bench, the Neo Phy Sci podcast of the incubator. I'm Misty Good, a neonatologist-scientist, and Division Chief at UNC Chapel Hill, and I'm co-hosting today with Dr. David McCulley. David, would you like to introduce yourself?

David McCulley (00:15.874)

Thanks very much Misty. I'm David McCulley. I'm a neonatologist and physician scientist here at UCSD and Rady Children's Hospital. I'm very excited to be a part of this program. Thanks Misty.

Misty Good (00:28.922)

Today we're really excited to host a wonderful neonatologist, scientist, and dear friend, Dr. Steve McElroy on our At the Bench podcast. Steve, would you like to introduce yourself?

Steven McElroy (00:41.164)

Yeah, thanks both Misty and David for asking me to be on this. So my name is Steve McElroy. I am a physician scientist and I'm the Division Chief at the University of California Davis.

Misty Good (00:53.826)

Awesome. We would love to hear all about your research. So if you don't mind briefly talking about your research and saying all of the great things that you do.

Steven McElroy (01:05.198)

My research focuses on injury and repair mechanisms in the immature intestine. And so what that basically means and has come out of it is, I realized early on in my career that things like necrotizing enterocolitis and spontaneous perforation seem to happen to premature infants, but they seem to happen not necessarily right at birth, but they happened at different developmental points and the different timing depended a little bit about when the babies were born, which to me meant that there was a developmental component to it. And so, I was really interested in understanding why the immature intestine was different than the term or even the adult intestine. And so my career is really focused on trying to answer questions along that line.

We've done everything from understanding how the intestine develops to things that impact it, like inflammation, bacteria, host protection peptides, such as antimicrobial peptides. And more recently, we've been looking at Chorioamnionitis and its impacts on how the development of the intestine happens and how it interacts. So it's been kind of fun to be able to look across all of those various things over time.

Misty Good (02:35.555) Awesome.

David McCulley (02:35.586)

Thanks. That was awesome, Steve. It's awesome to talk with you on this program. And I was curious just because I've gotten to talk with you and hear you presented at multiple different meetings. And now I get to see your trainees presenting at national meetings. So it's really exciting how far your research has come. I think it's always really interesting to hear what motivated people to start pursuing their particular research interests. And I can imagine coming up through pediatric training and in neonatology that there's got to be a good story behind your research interest. Is there a clinical story that helped get you started, or what motivated you to pursue this course?

Steven McElroy (03:16.492)

Yeah, so I am sure everybody who comes on this podcast says that research training is never a straight line. And mine definitely was not. I was never going to do science. So I actually had this conversation with my kid yesterday. When I was in college, I did a research project. I went to a small liberal arts college, Juniata College, and I did a summer project. We were trying to find new antimicrobials. And we went out into the surrounding area, and we dug up dirt, and we dug up different things, and we put them all together on agar plates. We were trying to find unique combinations of things that would cause bacteria to produce antimicrobial factors. And it was a lot of fun, but honestly, we drank a lot of beer and didn't really find much. And I walked away from that and said, I want to be a doctor. I don't want to do science because science doesn't seem to be moving things forward. And it wasn't until I was a fellow and, or actually, I wasn't a fellow, I was a resident at St. Christopher's Hospital for Children, and I knew I wanted to be a neonatologist. And I knew that I wanted to do academics because I liked to mentor and I liked to teach. And so I went to Maria Delivoria, who was the chief at the time. And I said to her, said, Dr. Delivoria, I want to be a neonatologist. I want to stay in academics, how do I do that? And she said, come to my lab. So, okay, because you didn't say no to Maria. And so I went to her lab, and, you know, Maria did a lot of outstanding work on early work on HIE and asphyxia. I did a short little project for her and got to present it at PAS. And it was revolutionary because I was like, this is really cool. Now I understand how science impacts clinical care and vice versa. So I was all in as a fellow, I'm going to be a physician scientist. And I went to Vanderbilt and nobody at the time was doing HIE work. And so then I was like, well, I don't know what I want to do, but I know I want to do the science thing. I looked at a bunch of different labs and settled on Brent Polk's lab because Brent was doing really outstanding epithelial biology work. And Brent was more interested in inflammatory bowel disease but we realized that NEC has a lot of similar cell signaling pathways. And so we thought this was a good way to go. So I went trained with Brent during fellowship, then stayed on as faculty at Vanderbilt. And then right after I got my K award, Brent was able to go to LA Children's and be the Chair, which meant I didn't have a mentor anymore. So then I had to struggle and figure out what I was going to do and how I was going to move forward with this K.

That really got me thinking about NEC and understanding what really was going on. And that got me to the developmental side. And what then really turned the tide for me was probably when I picked up a mentor with a gentleman, physician scientist by the name of David Bader. And Dave was a developmental biologist and he was a cardiac developmental biologist who had nothing to do with what I was doing, but being able to understand the developmental side of things and pair that with understanding intestinal biology and epithelial biology finally made sense for me. That's really what set me moving in my career pathway.

Misty Good (07:02.74)

Can we talk about that a little bit more? I know that several of our listeners are probably concerned about what they will do if their mentor leaves. Certainly, that happened to me in my career when I just received my K08, and my mentor and lab left. And so, can you talk a little bit more about that time? Did you feel like it was a struggle? Or did you feel like you had the institutional support that you needed to be able to pivot? Was it a dark time? Was it okay?

Steven McElroy (07:36.936)

Oh it was a dark time. My God, I was terrified. I don't remember which meeting it was, but I remember like flashpoint memories. Like I remember standing in this conference room with posters around me, getting a call that nobody knew who my mentor was going to be, and I had to find one or they were going to put me with this person that I didn't want to be my mentor. And so, I had to scramble to try and figure out things, which is where Dave Bader came in, and it was actually, you know, we talk about mentorship, and the misnomer is that you have like one mentor that does everything for you. And that's just not true. This is a perfect example because one or two of my really best mentors at that time were Lance Prince and Jeff Reese, who people in neonatology know these names because they're awesome people.  

Misty Good (08:28.984) They’re amazing.

Steven McElroy (08:32.76)

Yeah, amazing. I called them up because I was like, I don't know what I'm going to do. Lance told me to talk to Dave Bader because I thought he'd be a good fit for me. And that's kind of where that went from. You know, it's really scary when your mentor leaves, because your options are to either go with your mentor, which you may or may not be able to do, to stay where you are, and hopefully, there are enough people around you that your mentor leaving doesn't disrupt what you're doing or you have to pivot. And, I ended up having to pivot, but it worked out because I was supported enough by Vandy that I was able to keep going with my science. I have to give a lot of credit to my division chief at the time, Judy Aschner, because she was the one that really supported me and made sure that I moved forward. And also all of the side mentors that I had like Lance and Jeff.

Misty Good (09:30.33)

That's awesome. I’m glad you had that institutional support and I'm glad they took you in. That's great.

David McCulley (09:38.582)

It's also really exciting to hear just about how like a transition in mentorship like that, that's probably the best positive spin you can put on that, really helps to open new doors and give you a new skill set and maybe a new perspective on the research question that you were pursuing. And I wonder what you think about how that helped you then build your confidence, and build your kind of repertoire of your research toward independence. Could you talk about that, transitioning then to an independent investigator?

Steven McElroy (10:12.588)

Yeah. So, it was kind of like, it was trial by fire. I became independent well before I was supposed to be independent, I'm pretty sure. But part of the thing is that, it's helpful when your mentor is tied into your department because then you have leverage. My mentor was completely in adult medicine cardiology and not in Peds. So that made me a little bit more about the leverage that you would hope to have. Part of the deal, I think that has helped me out was somewhere early on in my career, and it was probably Brent told me that you should never, and I'll, you know, I will apologetically say this for both of you guys, and your science, but Brent told me, don't study a disease, because if you study a disease and they fix the disease, you're out of a job.

Misty Good (11:33.537)

I feel like we all get that advice, right? Everyone says don't study a disease. But you know, for me, I only care about NEC, so of course I'm going to study it.

Steven McElroy (11:37.421) Right?

Steven McElroy (11:42.221)

So I really took that to heart. And so if you go around and ask people about my science, the neonatology world thinks of me as a NEC person, but the science world thinks of me as a Paneth cell biologist or a developmental intestinal biologist, something along those lines. And so that's really allowed me to pivot probably more than anything because I'm not limited to just one thing, and I can flex around.

David McCulley (11:56.109) Yeah.

Steven McElroy (12:11.014)

The perfect example is some of the stuff that we're doing now is sepsis biology, which, you know, yes is NEC, but not really. And the Chorioamnionitis story again is tied into NEC and they overlap, but there's a lot of flexibility to look at different things when you're not tied down to one thing. And that, that helped me pivot, but honestly, the thing that really made the independence thing happen, was when I moved to Iowa.

So there came a point where, you know, I was struggling to get papers out, and my K was funded, but it was moving towards the end. And my Chair decided that I was not somebody that he wanted to keep funding. And so, I started looking around and ended up moving to Iowa, which was a fantastic opportunity for me. But then, I was truly independent because I moved out, and while I still had mentorship and actually, it was awesome mentorship because I started working with Jessie Moreland, who's a PICU doc and a neutrophil biologist, and she really helped me understand the inflammation side of the stuff that I didn't really have before. But that move made me have to be independent because I no longer was buried in somebody else's lab.

So was my lab, it was my techs, it was my reagents, my microscopes, my everything. And so that really kind of forced the independence piece. And so I think sometimes you get independent because you have to. And so I think that's part of the independence piece. The other thing is, when I was at Vanderbilt, I was changing tracks. I started to do the old NEC model that I know Misty loves to death But, it's really hard, right? I failed at that model for a long time.

And part of it was it was just me and one technician. And that model is really hard to do when you don’t have a fleet of people. It's almost impossible when you have two. And so we started looking for other models to use.  

Misty Good (14:09.274)

I wouldn't say I love it. I have a love-hate relationship with it, I think.It's brutal.

Steven McElroy (14:32.098)

It meant I had to do a lot of really crazy things like putting G tubes and baby mice and trying to figure out how to milk mice and doing all these various things. And going through those things, I think helps independence because you're really trailblazing. And those you kind of pick up your independent traits as you do that.

Misty Good (14:54.53)

Yeah, the model is just a lot. I'm grateful for all the folks in my lab who feed the mice, not quite around the clock, but pretty close. I was going to ask you, what was it initially that got you excited about Paneth cells? Because you have really pioneered the Paneth cell ablation necrotizing enterocolitis model. And you touched on it a little bit and you talked about developmental biology, but maybe you could expand a bit more about that. Like what got you excited? What got you interested in Paneth cells?

Steven McElroy (15:29.592)

So I was giving a talk at the PAS meeting. I was standing up and

I was talking about goblet cells. I had done this study where I looked at human tissue samples of kids that had developed spontaneous perf and kids that had developed NEC, and then some older kids and was looking at the various cell types. And I was about 98 % ready to get out of the NEC field altogether because like I said, I couldn't get the feeding and hypoxia model to work. And so I was standing up, and I was presenting all this goblet cell stuff and I had one slide that had Paneth cells on it. A gentlemen raised hand in the back, came up with Mike and asked the question. And this was Mike Sherman who's passed away, but Mike stood up there and he said, this was fantastic work. Can you tell me more about the Paneth cells? And I, you know, very suavely passed it off because I had no idea how to answer this, right? So we've all been there and right. That was exactly it. We found that there was a decrease in Paneth cells, too. And I said that's an awesome question. We'll have to look more into it or something like that. But the important thing, exactly. But the important thing and what I tell people all the time is it's really important to listen and go ask questions. Go talk to the people that ask you tough questions. So I went up to Mike afterwards, and I talked to him and he was asking this because he had done this study where he was interested in Paneth cell biology and he had depleted Paneth cell with this chemical called dithiazone, which is a heavy metal chelator. And he was really interested to see if you got rid of Paneth cells, if you would have a higher rate of tissue penetration with E. coli. And he had done this study and published it. And as it turns out, in like four of his rats, he had done it, baby rats, four of his rats had something that looked like NEC. And he said, well, you know, Steve, this is really interesting to me because I have this. And I said, that's really interesting to me. Are you going to do anything with it? And he said, no. And I said, that's cool, can I? And he said, yes. And so that's really where that came from.

Misty Good (17:44.611) Nice!

Steven McElroy (17:49.07)

And so then the next, I don't know, probably several years, we converted that rat model into a mouse model, and moved it forward and really developed the model that has been the basis of probably, two thirds of my career, which is understanding this new model of NEC where you deplete the Paneth cells. And it's a two hit model. You have to deplete the Paneth cells and then cause a dysbiotic inflammation also. But it's a really developmental dependent model in that if you do it before Paneth cells develop, it doesn't work. And if you do it at term equivalency, it doesn't work. And so it's been kind of a fun thing to look at and understand. And just getting to know Paneth cell biology has been fun and talking with all the people that do it from a stem cell standpoint and trying to bring that to be more translational. It's been a cool part of the career and part of the journey.

Misty Good (18:50.778)

That's awesome.

David McCulley (18:52.024)

That is awesome, Steve. And I think just hearing this story, it's really helpful because I think people come up generally tend to think of people who are doing science as being kind of in a silo. Like you could think that you're a NEC biologist or I was thinking of you as like a developmental intestinal biologist and then had this interest in Paneth cells. And it seems like an unusual cell population. So it's been really exciting to see you make progress in studying it. But I think it's also really helpful to just show that you get to go across these barriers. I think thinking creatively about trying to address these questions that we have based on clinical scenarios and then developing a mentoring team, developing a research interest that allows you to answer those questions is really the way we make progress. But then to keep doing things that are novel and interesting, you just keep crossing these barriers and asking questions that are slightly new or a different perspective. I was just wondering, just more recently, since you've moved from Iowa to UC Davis and now you're the Division Chief there, do you have like a new perspective or how is moving from Iowa to UC Davis changed your research trajectory?

Steven McElroy (20:10.638)

Yeah, every time you move, it changes your trajectory. So if anybody tells you that that's not true, they're just lying.

Misty Good (20:16.642)

True, so true. It's so hard.

David McCulley (20:26.466) Challenging.

Steven McElroy (20:40.482)

Because every place is good and bad, but they're good and bad in different ways. So, Vanderbilt was awesome because they had more cores than you can shake a stick at, and it was easy to be able to interface with them. But it was a little harder to get to know all of the big movers and shakers when you were a really junior person. Iowa is awesome. It's got a really deep, long standing history of good science. And it was easier to connect with people than it was for me at Vanderbilt, but they also didn't have a deep GI program. And so I ended up having to really spread collaboration wings.

And so that has been awesome for me. I now collaborate with people internationally and people all over the US. I think most of my papers have collaborators, probably more collaborators on it than it does my own people sometimes. I think that's a strong thing. Moving to Davis, they have an incredible veterinary program out here and an incredible nutrition and milk biology program. So it opens up doors that I didn't have previously. But again, every place has good and bad and things. And every time you move, it takes a while to get things geared up and going again. So, there is definitely an inertia problem when you move. You have to spend a lot of energy to get things up and going again. But that being said, there are all kinds of possibilities that you get when you move that you didn't have before you moved. And so one of the cool things about doing science is that it allows you to ask new questions in new ways. And sometimes moving is the only way you can really access some of that.

Misty Good (22:20.558)

I think that's a really good point. And we know that you moved to UC Davis for your leadership role. So we want to talk a little bit about that and then let us know, what do you like about your current role? And then how does your new role impact how you do science and the way in which you do science and mentor perhaps differently based on your availability?

Steven McElroy (22:43.736)

Yeah. So I think when I look back at my career, the things that really I find the most fun, the things that get you out of bed and moving are, are building programs and mentoring people. Like those, those are the parts that I do for free because they're just fun. and as I've taken on the division leadership role, that's just shifted those things. They're a little bit of a greater magnitude now because as opposed to building the program in your lab, you're now building it for a division, and you're trying to move forward clinical pieces as well as research pieces, and the mentorship piece becomes now more trying to help your people succeed and empower them to grow and really do the awesome things that they want to do.

Whereas when I was doing it with just my lab, it's just moving students forward to the next thing. And so it's a little more stress because you're dealing with kind of bigger stakes. But, there's bigger reward and payoff too. So I think that's part of it. There is absolutely an impact of taking on a Division Chief role on your science because you're now doing, instead of doing two full-time jobs as a scientist and a clinician, you're now doing probably five, depending on how much you get involved with. But you at least have three full-time jobs and the science need doesn't end. So you end up doing science a lot on the side. You have to get better with time management.

Misty Good (24:20.537) Yes.

Steven McElroy (24:36.622)

You also have to be good with communication with your people because they have to realize that you can't sit in the lab 70 % of the time like I used to when I wasn't a Division Chief. I think that you have to shift how you do things. That's one of the cool things with academic medicine is that, you're always able to kind of shift and move through your career and try on different things. And so I think that's a challenge, but that's one of reasons why we stay in academics.

Misty Good (25:09.464) So true. I love that.

David McCulley (25:10.754)

That's a really good point. One of the things we're trying to do by hosting this program and talking with neonatal physician scientists is trying to stimulate people who are early in training to consider this as a career path. And I think that flexibility is something that we're trying to hint at or at least discuss, if not directly, kind of indirectly by just demonstrating it. But I think, you know, hearing that from you is really helpful just because I think that is a huge benefit. We get to kind of move a little fluidly based on our interests, where the problems are and think creatively about them. And we have to think creatively about how we are going to move our research forward. We can change what we're doing on a day-to-day basis to deal with new problems that are more clinically oriented or more translationally oriented or definitely at the bench. But I think that hearing that from you is really helpful.

Is that something that you talk about directly with your trainees, or just for people that are interested in a physician scientist path, that you are able to have a lot of flexibility. And if you're a creative person and you like thinking about new challenges, is that something that you highlight in the mentoring you do with your trainees?

Steven McElroy (26:29.262)

Probably not as much as I should because I think usually it's the people that come find me that have that already instilled. But I think it's a really good point. There's so much talked about in neonatology right now about wellness and time and all those things.

And the reality is, as I was coming up through, even though I was working a lot, right, because to be a physician scientist, you got to work a lot and you have to put a lot of hours in, but it's more flexible because when you're on service, you show up at a specific time and leave at a specific time, hopefully, and there's no flexibility there because you're taking care of tiny humans. When you're in the lab, some of the experiments are going to determine your time, but there are a lot of things that have convenient timing, right?

Steven McElroy (27:25.772)

So you can run this experiment to X amount of time, and then you can step away if you need to and come back to it, or you can start it later. You know, when when my kids were little, there were a lot of times where I would go to their performances or various other things, go to meetings, and I just moved the timing of what was going on in the lab around it so that I could have that flexibility. And I think that's a really important piece.

Now, the other piece is that we only get new knowledge in medicine from science. QI doesn't give you new knowledge and clinical trials still have to get their hypothesis from basic science. And so that's not to say those things aren't important because those are super important too.

David McCulley (28:21.112) Yes, that's good.

Steven McElroy (28:22.446)

But the development of the new knowledge has to usually come from the wet lab or somebody that's trying to develop some mechanistic study. So if you're somebody who is really interested in why things happen and how things happen, then using bench science as the tool to get at that can be really satisfying.

David McCulley (28:45.848)

That is such a good point. I think we cannot stress that enough just because you're studying a really heterogeneous disease, like we've been talking about that through each of the shows that we've hosted, that many of the diseases we're trying to understand the pathophysiologic mechanisms of are so heterogeneous to do a clinical study and say that all patients with NEC will benefit from this or should be treated this way. It's so difficult, but in a lab you can control so many more variables and just change one subtle thing at a time to really try to understand the mechanism a lot more carefully. So I thought that was a really good point.

Misty Good (29:23.92)

I think it's a good point to talk about just how flexible it is to be a physician scientist. I wanted to switch gears a little bit and talk about your current funding. And you glossed over it earlier, but you are studying chorioamnionitis, and we know you're R01 funded, and you're an outstanding investigator. We really want to hear more about your current work and what gets you out of bed in the morning currently related to that.

Steven McElroy (29:59.17)

My alarm clock! No, our current work that we're doing in the lab. So, funding-wise, I'm funded with an R01, and I'm also very fortunate to have an endowed chair position here at UC Davis. So that always is a wonderful source of funding when you reach the medium to senior level of things. But the R01 that we're looking at is really trying to understand the basis of why kids that were exposed to chorioamnionitis in utero have an increased susceptibility to developing NEC. That used to bother the heck out of me because it makes no sense. You're exposed to all this inflammation as a fetus, and then you come out, and you're normal. Well, I mean, as normal as our preemies are, right? And so why are you weeks later susceptible to developing this disease? And some of this actually came out of mentorship talks; I was talking to one of the fellows, and we were trying to figure out spontaneous intestinal perforations. And there's no good model for that. And we were just kind of talking about different things, and it got into chorio. And then it evolved into this Chorio-NEC business. And so, we started thinking about it, and I started thinking about it. And it really became, again, a developmental biology question. So if it's not an inflammatory thing, because none of the cytokines should hang around that long, then you must be changing the developmental trajectory of the intestine. So then that got me digging around into a lot of the literature. And it was really two things that happened kind of similar in time that brought this all together. So one was an article that came out, and this is why it's important to read kind of widely. Look around and listen to other people talk. But there was an article that came out that was in adult tissue that was looking at Paneth cell biology. And they found that if you exposed the intestine to inflammation, then through an interleukin-6 pathway, it would create downstream an interferon lambda cytokine upregulation. And that then caused death of the Paneth cells.

And I was like, wow, this is super cool. Maybe this is part of it because interleukin-6 is a major product of chorioamnionitis. And what tends to happen, I think, at least for me, and I think this is true of a lot of people in science, is you have to let that kind of gestate around in your head for a long period of time. And so I was kind of bouncing around how this would all work and how to put this together. One of the key concepts that we do not pay enough attention to is that we have to have creative think time to allow these things to kind of gel. If you don't build that into your schedule, you're going to eventually crash and burn.

Misty Good (33:10.906)

There was just an article about this In Nature that just came out about how scientists need time to think.

Steven McElroy (33:19.114)

And this is the perfect example, because I wrote the specific aims for my R01 while I was sitting in a orchestra concert. And I was waiting for my kid to play, and I was just kind of zoning out, listening to classical music and it came to me and I just started scribbling. And I think that's really critical that that's how sometimes science works. But we're basically looking at a couple of

models of chorioamnionitis, and we're trying to figure out exactly this mechanism of how exposure to inflammation as a fetus then predisposes the intestine to be more susceptible to injury. And it does look like it works at least in part through Paneth cell biology. And so we're excited to move that forward. And, we've been able to do lots of cool things and have lots of different collaborations, both with long time collaborators and new folks to really get after this. I think that's one of the exciting things about doing science is to be able to work with people and generate new knowledge.

Misty Good (34:28.314)

I have question about that. Do you think that it's related to the specific type of bacteria or do you think it's just related to the inflammatory response specifically or the signaling pathways?

Steven McElroy (34:39.64)

Yeah, so it's a great question. There are tons of ways to model chorioamnionitis. And I specifically avoided the bacterial ones, much to the chagrin of some of the Chorio people. But I didn't want to mess around with live bacteria in this. I really only wanted to cause inflammation. So our model is one where you inject lipopolysaccharide into the pregnant mom. And so that induces a robust inflammatory response that's very similar to what we see in pretty severe chorio. But it does it without bacterial impact. And so it's a nice way to generate data. In fact, we don't call the model a chorio model. If you look at the papers, we call it FEMI, which is fetal exposure to maternal inflammation, which is a really bad acronym, but it's what we picked. And so we just stick with it now. But, you know, that gets around that whole piece. I think that there are lots of ways that you can induce inflammation. And I think the trigger, at least in our hands, is through interleukin-6. So as long as you're doing that, I think it probably doesn't matter what the organism is that's inducing the inflammation.

Misty Good (35:57.898)

Well, it will be interesting to find out more as you dig into that signaling pathway.

David McCulley (36:05.034)

It has been exciting, though, because it seems like you're making progress in this, and now it seems like you're trying different things that would actually be potential treatments. Are you thinking that way or is that really more just like trying to better understand the mechanism? Like I think a lot of times we use rescue. It sounds like it could be translational, but it also really helps to understand like mechanism of injuries. What, do you think about that?

Steven McElroy (36:31.554)

Yeah, think that I am more a mechanism person than a treatment person at the end of the day. I think all scientists realize kind of what their lane is and they try and stay in it. I am a very translational biologist. Basic science people think that I'm way clinical and the clinical people think that I'm way basic, which tells me that I'm translational. And I really appreciate the people that can take science and move it towards treatments and patient level care. I have not been uber successful in doing that, although I've dabbled in a little bit. But where I find my sweet spot is really just trying to understand the mechanistic piece, especially using mouse models. And so that's a step up from organoids and cell culture and very specific mechanistic work that way, because you're taking the whole organism in mind. But I think the amount of treatment still to me is looking at things that will fix the model in the mouse versus I want to take this directly to the humans, which is just a new concept that I haven't gone far into. So I think that I have much more of a mechanistic side than the treatment side per se.

Misty Good (38:10.03)

That's awesome. I'm going to pivot a little bit and ask you what advice you could give for early stage investigators, you know, that are maybe in it, maybe they're in a dark place, they're in the struggles. What are your pearls of advice for them on getting through and continuing on in this journey?

Steven McElroy (38:40.654)

So I recently gave this talk at the Southern Society for Peds

Research. When I think about this, I think about a couple of things. The first is that I talk about baseball as a concept. Not that I'm a huge baseball fan, but as a concept. And the greatest hitters in baseball are averaging like 30 % batting averages-ish, which means that's the pinnacle. All the Nobel Prize winners in our fields, and they're missing all the time and so I don't get too bent out of shape when things don't work because that's part of the process, or I try not to get too bent out of shape. Everybody gets bent out of shape, so I think part of it is understanding what you're doing and that if things aren't working, that's normal. I think that it's really important to celebrate the wins. So when you have a win and whether that's your thing worked, or you got data, or you got a manuscript out, or you wrote a grant, that's amazing. And you got to celebrate it because there are more things that go wrong than not. I think it's really important to have strong mentorship.

So for early people, you have to have a group of people that are solidly behind you. And it's usually not just one person, it needs to be like multiple people. And you have to have really strong communication with them. So I think that's important. And you have to have a network of peer people too, because you need the people that you can call up and say, I just had a terrible day; I don't understand; my Division Chief is a jerk, it is not working out, blah, blah, blah. We all have been there. So I think that's really important. And then the other thing is you just have to keep doing it. And if you don't like it, then you should probably do something else because it's a lot of just being persistent. There have been many, many, many, many, many times that I thought the wheels were off, the cart was crashed, and everything was going to stop. And I'm either too stupid or too stubborn to quit. And so, right, I mean, it's one of those, but it's true. Like I just keep going and keep trying. And part of that is just because I don't.

Steven McElroy (41:34.222)

And I think that's a really important trend and aspect, but it's also important to know that you just have to keep at it because success is not fast in science. It takes a long time. I remember when I was early in this and being irritated that people weren't recognizing the work that I was doing because I was doing good stuff, right? And why am I not being asked to talk about these things or why are people not listening? The Paneth cell biology was a thing for almost a decade. People really thought that my model was not even NEC. And it took a lot of persistence to get to the point where people were like, yeah, no, this model is relevant and important. And I think that persistence is so critical because there are just so many times that things aren't working. And it's okay. That's part of the deal. What matters is that you get up the next day and you do it again. I think that's what the old time people used to call the fire in the belly. Millie Stallman used to say that all the time and she would say, you have to have the fire in the belly to do science.

Misty Good (42:47.248) Yes!

Steven McElroy (42:55.318)

And I was like, what are you talking about? I don’t even know what that means, it's like heartburn. But I think what she was talking about was this concept of you just really want to kind of find the answer. And it's okay to keep going back to it and trying in different ways and repeating what you did in the past and just keep after that question.

Misty Good (43:19.876)

I agree. I think it's so important. We call it resilience now, right? The fire in the belly. It's like, you just keep attacking the problem in any way that you can and get up the next day and just keep fighting and asking the questions and, really trying to find the answers that we seek. I think that's incredibly important because you have to. But I also tell my mentees, there's so much rejection in science. And one of the things you have to remember is you do have to get up the next day and do it, and you're allowed to be sad, but for just one day. For example, if your paper gets rejected or your grant isn't funded, And you're right about the baseball theory. It actually makes me feel better about a lot of my grant rejections. So, thank you for that analogy for all of us that have, you know, submitted three grants that haven't been funded or, you know, five grants that haven't been funded.

Steven McElroy (44:16.44)

Yeah. You know, the other thing that was told to me, Akhil Maheshwari, told me this once, and it really has stuck with me. He said, look, if you want to have a painting in the museum, you better not paint one. And I was like, man, that's so true. Like if you think you're just going to do it once and be done, you're in the wrong field. But it's okay to be sad because it's creative. I mean, this is art.

Misty Good (44:31.78) So true.

Steven McElroy (44:44.472)

Half of what we're doing is you're pouring your soul into this art that you're doing, which means when somebody tells you it's not good enough, that's devastating. And that's, I don't care who you are, that's true across the board. So it takes a while to recover from that. That, again, is part of it. You have to really develop this thick skin that you're okay with constructive criticism at a high level of something that you thought was amazing.

David McCulley (45:18.956)

I totally agree. I like all of the points you made there, Steve, but I also really thought, like what you said in the middle of that, where you were saying, celebrate the small victories, because I think that is really important. We tend to quickly move on to the next major stressor, but take a second just to be happy. And then also what you were saying earlier about giving yourself room to think creatively, like you were describing at your child's orchestra concert and just realizing you could make progress on your specific aims.

That is really important because I think we have to be able to think creatively. And if we're constantly bombarded with things and don't take the time, mental space for that, it's very hard to make progress. We are kind of getting to the end of our time. And we've been closing with talking about things that make us human. And I was just curious if there's something that your group likes to do for fun or that your research group does together.

Like is there something that makes your lab environment awesome or anything you'd like to share?

Steven McElroy (46:24.184)

You know, it's varied as the lab has moved and it's evolved. And I think that's true with lab groups. But you know, I think over time things have stuck out. When I was at Iowa, we made sure that whenever anybody had a manuscript that went out or when we came back from a meeting or we had any win, we would go out and we'd have breakfast.

And we'd do lab meeting at breakfast or I would just pick that up so that the trainees weren't paying for it. The funny thing was we would go for - those of you out there who've been to Iowa city - one of the famous diners is called the Hamburg Inn and they, have pie shakes and it's basically a milkshake that they throw a slice of pie in it or a slice of cake and grind it all up. And it's amazing. And the undergrads, that's what they would go for.

You know, we have done various things. I know one of my mentors along the way used to have champagne that she would pop when anybody in the lab did well. I think it doesn't matter as long as you try and do something again to support the wins. You have to have fun with this. And whether that's a website, you know, a lab logo.

You know, those kinds of things are things that people can kind of get behind. Yes, exactly. As Misty has right there. I mean, you have to have this, right. You have to have those things that kind of make it fun. Trying to take people with you to meetings and make that fun, I think is important too, because then you get to see kind of that side of it and making.

Misty Good (47:50.18)

Here’s the Good Lab logo. I love it. Shout out to my technician.

David McCulley (47:55.65)

Wow.

Steven McElroy (48:17.598)

This is making everybody human, which I think is important. Here in

Sacramento, we sit on a couple of rivers. So we've gone out and been on river barges with the lab. We have been talking for a while about going out on it. What? You know, it's pretty attached. It's okay. But you know, things like the beer bikes that ride through town, that's on our to do list coming up.

Misty Good (48:33.37) Sounds dangerous.

David McCulley (48:37.506) Gotta live.

Steven McElroy (48:44.586)

So I think anything where you can have those sorts of events where you can get everybody together and hang out, I think is important. Lab work is a lot of trust. And so the more you hang out with each other, the more you trust each other and the more that it works out.

Misty Good (49:02.074)

I think that's such a great point. And thank you for sharing all of that, Steve. And we're really grateful for you coming on the podcast and telling us about all your amazing work and giving our early stage investigators something inspiring to think about and motivate them to keep going and find that fire in their belly. So we appreciate you and thank you so much.

Steven McElroy (49:27.992)

Absolutely. Thank you guys for having me on and thank you for doing this. I think this is a really cool and important thing for early career folks to hear how this works for people that have been doing it for a little while. I'm a little weirded out that I'm now considered like a senior person, but that's okay.

Misty Good (49:46.256)

No, you're awesome. Thank you again.

David McCulley (49:51.362)

Thank you so much, Steve. Great to talk with you.

Steven McElroy (49:53.923) Thanks guys.

Misty Good (49:54.072)

All right, take care, everyone.