#369 - 🔬 Building Bridges Between the NICU and the Lab with Dr. Eleanor Molloy

Hello friends 👋

In this episode of At the Bench, Betsy Crouch and David McCulley engage in a thought-provoking conversation with Dr. Eleanor Molloy, a neonatologist and physician scientist. They explore Eleanor's journey in neonatology, the importance of inflammation in neonatal health, and the challenges and rewards of conducting research in this field. The discussion also highlights the significance of collaboration, both within research teams and with parents, to enhance clinical practice and improve outcomes for neonates. Eleanor shares insights on the role of biomarkers, the impact of sex differences in research, and the necessity of international collaboration in pediatric research. The episode concludes with reflections on the balance between clinical work and research, the importance of community in academia, and the need for a rallying call to inspire the next generation of clinician scientists.

Link to episode on youtube: https://youtu.be/v70XmSL2TYg

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Short Bio: Dr. Eleanor Molloy is the Professor and Chair of Paediatrics and Child Health in Trinity College Dublin, Ireland. She is a paediatrician and neonatologist based in Children’s Health Ireland at Crumlin & Tallaght and the Coombe Hospital. She qualified in Medicine in UCC (1993) and received her PhD from UCD in 2003. Her research group is concerned with interdisciplinary child health research and the promotion of Paediatric Translational projects to improve child health and she is co-director of the Trinity research in childhood centre (TRICC) with> 100 principal investigators.

She is co-lead for the Health Research Board funded In4Kids the national paediatric clinical trials network aiming to facilitate access to clinical trials for children in Ireland. The Molloy translational research laboratory  in TCD evaluates new methods to modify the immune responses newborn infants with brain injury through their childhood to find new therapies to improve their outcome by modifying persistent dysfunctional inflammation.

 Internationally she has served as the Secretary & President of the Irish American Paediatric Society and as the Irish representative on the European Board of Paediatrics: European Union of Medical Specialists (UEMS), Confederation of European Specialists in Paediatrics (CESP), Board member of the European Society for Paediatric Research and Newborn Brain Society. She was awarded Honorary Fellowship at the American Paediatric Society, a Professorial Fellowship by Trinity College and is the Associate Editor in chief for the journal “Paediatric Research” on behalf of the International Paediatric Research Foundation since 2015.She has supervised more than 20 PhD and MD thesis students and have over 300 peer reviewed publications. She is interested in collaborative research encompassing consensus definitions of terminology related to neonatal sepsis and measuring core outcomes so that research data can be shared to improve outcomes for children.  She is developing programmes in multiorgan care as well as functional motor care from the newborn period to adulthood following neonatal brain injury,  sepsis  and cerebral palsy in partnership with families and with funding from Science Foundation Ireland and the Health Research Board.

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Featured Manuscripts From Dr. Molloy:

McGovern M, Kelly LA, Finnegan R, Murphy JF, Kelleher J, Melo AM, Greene CM, Molloy EJ. Sex differences in preterm cytokine and inflammasome responses and modulation by exogenous sex steroids. Pediatr Res. 2025 Sep 24. doi: 10.1038/s41390-025-04350-0. Epub ahead of print. PMID: 40993359.

McGovern M, Kelly L, Finnegan R, McGrath R, Kelleher J, El-Khuffash A, Murphy J, Greene CM, Molloy EJ. Gender and sex hormone effects on neonatal innate immune function. J Matern Fetal Neonatal Med. 2024 Dec;37(1):2334850. doi: 10.1080/14767058.2024.2334850. Epub 2024 Jun 5. PMID: 38839425.

Molloy EJ, Branagan A, Hurley T, Quirke F, Devane D, Taneri PE, El-Dib M, Bloomfield FH, Maeso B, Pilon B, Bonifacio SL, Wusthoff CJ, Chalak L, Bearer C, Murray DM, Badawi N, Campbell S, Mulkey S, Gressens P, Ferriero DM, de Vries LS, Walker K, Kay S, Boylan G, Gale C, Robertson NJ, D'Alton M, Gunn A, Nelson KB; Steering Group for DEFiNE (Definition of Neonatal Encephalopathy). Neonatal encephalopathy and hypoxic-ischemic encephalopathy: moving from controversy to consensus definitions and subclassification. Pediatr Res. 2023 Dec;94(6):1860-1863. doi: 10.1038/s41390-023-02775-z. Epub 2023 Aug 12. PMID: 37573378.

Zakharchenko L, El-Khuffash A, Hurley T, Kelly L, Melo A, Padden M, Franklin O, Molloy EJ. Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses. Pediatr Res. 2022 Dec;92(6):1716-1723. doi: 10.1038/s41390-022-02000-3. Epub 2022 Mar 29. PMID: 35352006; PMCID: PMC9771806.

Ryan E, Kelly L, Stacey C, Huggard D, Duff E, McCollum D, Leonard A, Boran G, Doherty DR, Bolger T, Molloy EJ. Mild-to-severe traumatic brain injury in children: altered cytokines reflect severity. J Neuroinflammation. 2022 Feb 7;19(1):36. doi: 10.1186/s12974-022-02390-5. PMID: 35130911; PMCID: PMC8822689.

Sweetman DU, Strickland T, Isweisi E, Kelly L, Slevin MT, Donoghue V, Meehan J, Boylan G, Murphy JFA, El-Khuffash A, Molloy EJ. Multi-organ dysfunction scoring in neonatal encephalopathy (MODE Score) and neurodevelopmental outcomes. Acta Paediatr. 2022 Jan;111(1):93-98. doi: 10.1111/apa.16111. Epub 2021 Sep 22. PMID: 34528287.

Kelly LA, O'Dea MI, Zareen Z, Melo AM, McKenna E, Strickland T, McEneaney V, Donoghue V, Boylan G, Sweetman D, Butler J, Vavasseur C, Miletin J, El-Khuffash AF, O'Neill LAJ, O'Leary JJ, Molloy EJ. Altered inflammasome activation in neonatal encephalopathy persists in childhood. Clin Exp Immunol. 2021 Jul;205(1):89-97. doi: 10.1111/cei.13598. Epub 2021 May 2. PMID: 33768526; PMCID: PMC8209598.

Molloy EJ, O'Neill AJ, Grantham JJ, Sheridan-Pereira M, Fitzpatrick JM, Webb DW, Watson RW. Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone. Blood. 2003 Oct 1;102(7):2653-9. doi: 10.1182/blood-2003-02-0649. Epub 2003 Jun 5. PMID: 12791649.

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

Betsy Crouch (00:02.178)

Hi everyone, welcome back to At the Bench, the physician scientist segment of the Incubator podcast. We're delighted to have you today as an always. I'm Betsy Crouch, I'm a neonatal physician scientist at UCSF. And I'm joined here today by my co-host, Dr. David McCully, and by our esteemed guests who we're delighted to talk to from across the pond, Dr. Eleanor Molloy. David, would you like to introduce yourself and get us started?

David McCulley (00:30.055)

Sure, thank you very much, Betsy. Yes, again, it's our honor to be able to host these podcasts and to try to give some insight into what it takes to become an outstanding neonatal physician scientist. I am a neonatologist and a basic developmental biologist here in California, University of California in San Diego. I study lung development. And again, I'm thrilled to be able to talk with the guests that we have been able to invite. Today I'm very excited to be able to introduce Dr. Eleanor Molloy, who is a neonatologist and physician scientist in Ireland. We have been collaborating together on a meeting that's going to be happening for the first time coming up in February with a joint collaboration between the European Society for Pediatric Research and the Society for Pediatric Research in the US. She is an outstanding advocate for physician scientists, and we're just so happy to have you join us on the show today, Eleanor. Would you mind just giving a quick introduction into who you are and we'll follow up with questions about what's motivating you and the work you do.

Eleanor Molloy (01:34.368)

Thank you. So thank you so much for inviting me. I'm a huge fan of the show and your podcast. So my name is Eleanor Molloy. As I said, I'm a neonatologist based in Dublin in Ireland, and I'm also a clinician scientist and I'm very interested in immunology of everything to do with babies.

David McCulley (01:59.172)

Excellent.

Betsy Crouch (01:59.202)

There are so many fun topics to discuss today. I think the breadth of your research is really exciting. Maybe we'll start just by asking you how you got started in neonatology. I saw that you were a neonatology fellow at Rainbow Babies in Cleveland. And I'm curious how you arrived there and then how you became established in Ireland.

Eleanor Molloy (02:35.922)

I sometimes wonder too actually. My husband is a physician, he's a surgeon and he got a fellowship in Cleveland, Ohio. And I went with him and I was really lucky to go to Rainbow Babies, which was the number one NICU in the States at the time. I was immediately given the textbook at interview. I was very impressed and it was a wonderful time to be there. So I was there for a few years and got to work with Dr. Fanarov, Richard Martin, Maureen Hack, Cynthia Bearer. It was amazing and we had a great time. I also got to do a postdoc when I was there with Claire Doerschuk in neonatal inflammation. So it was a fantastic time. And I think what's really lovely about the American Fellowships is that you are always their fellow. So many years later, I'm still invited at PAS to the gatherings.

And when Cynthia Bear was looking for someone who was European to do the editor in chief with her for Pediatric Research, she contacted me. And that's how I've been in that journal, Pediatric Research for the last decade because of my fellowship. And then going on from there, I suppose we always wanted to come back to Ireland, as many Irish people do. And I was lucky enough to get a job. And my first research fellow was Afif El-Khuffash, I think. He was a fantastic thesis student. And after him then we just continued. I originally didn't have an academic position for about five years. And then about 10 years ago, I got a chair position, which was fantastic. And then I could have my own lab. But my supervisor was amazing. He was a scientist who let me bring my PhD students to his lab.

It was many years until I got my own lab, so that really really helped. And now we're really lucky we have two postdocs and five to eight PhD students for all clinicians all the time so it's great to be able to have that opportunity.

David McCulley (04:43.759)

Eleanor, can I back up a little bit and just talk about how you got interested in neonatal inflammation and immunity and just how your research program got started? I mean, you had some leaders in the field in multiple different aspects of neonatology, and I was wondering what it was about inflammation that was inspiring to you or interesting or something that you thought you could pursue.

Eleanor Molloy (05:07.671)

no, that's great. I think what happened is, again, because I had finished my Irish training in the anatomy, I had a little bit of a hiatus time where my husband was not going to go to America for a couple of years. And at that time in surgical training, everyone did a PhD, but you didn't in pediatrics. So I was very lucky that his mentor, research wise, became my mentor and I was supposed to go to his lab to learn how to do a couple of techniques before I went somewhere else to do a PhD or a thesis. But actually, I ended up getting a grant and staying with him and he was a neutrophil biologist. So even though he is now an expert in prostate cancer, his name is Dr. William Watson, his original love had been neutral biology. And so that's how I started. And they were very kind to me, letting me do neonatology research in their prostate cancer lab. 

I was probably kind of quite a senior fellow at that stage, but I really got interested in it. And as we were saying earlier, David, it really made me ask questions about everything in the clinical realm, because I realized that nothing is perfect.

David McCulley (06:18.853)

Yeah, I think that's one thing that is so helpful to learn about from science generally is it teaches critical thinking. So just the way that we approach questions in our research experiments and in the lab, and in general, that approach trickles over into everything that we think about. We don't take for granted that something that someone says is really based in any sort of evidence or has a fact base behind it. We really try to find that evidence and think about it critically and then build supporting data that helps us come to a conclusion. So I think that that's really exciting to hear. And also just the point that you made about the opportunity to do research that was related to neonatology and neutrophil biology in a lab that was doing something entirely different, because you can learn from people who are doing great science. It doesn't have to be exactly in the thing that you want to do related to neonatology. You can learn how to do science from somebody else who is using the same techniques but in a totally different field. That is interesting for people to know more about too.

Eleanor Molloy (07:29.119)

Absolutely. I think that if you can collaborate as widely as possible, it's really good. And of course, then it's people you become friends with that you want to do research with and you meet at meetings. And I think you've been talking to other people about advice they give. And I think it's just to take all those opportunities and just really kind of see what they're doing. And I think as well in neonatology, we end up having to look at a lot of adult literature and adult research because that's probably where there's more funding anyway.

It's always extrapolated, but we can learn things in both directions. So I think it's great to meet as many scientists as you can.

Betsy Crouch (08:09.838)

Do you have a particular story about something that you encountered either in the prostate cancer lab? I was the neonatologist moonlighting in the prostate cancer lab. But something from that particular experience or just in general, as you mentioned, that there was an idea or a trial or a hypothesis from the adult literature that inspired you?

Eleanor Molloy (08:41.099)

Well, it's really interesting. It was a big joke that the only organ neonates probably didn't use or worry about was their prostate. But they did do a lot of renal dysfunction in the lab. So that was good. So and you could see sometimes the urology experts who came in to hear about prostate research would be a little bit sad when it was me talking about babies. But actually what I did find, though, and I think we find this all time in research is that my best publications, as in the highest ranking that came out of my thesis, were all my adult controls. So looking at gender differences in adults, immune function, got me much better publications than all those nights collecting cord blood in the middle of the night from patients with neonatal encephalopathy which took me three years to gather. I was determined to get published, but the adult stuff was so easy. But I think what was brilliant about that lab is my supervisor, he was very good at organization. So it helped me run a lab afterwards because I just copied what he had done. You know, the regular meetings, the way he structured the lab, the way he organized things was excellent. That really helped.

Betsy Crouch (09:50.487)

Tell us more about that. I mean, I think we have a broad audience, which is beautiful. And I really enjoy, you know, now we run into people across all areas of neonatology who have said, I listen to your podcast, which I enjoy. And I really like getting the feedback. But I think there's a group of us who are early, you know, principal investigators who could really benefit from more tips on expert organization in the lab.

Eleanor Molloy (10:19.877)

Now, I can't say that I have expert organization in the lab, but we would meet very regularly. And I suppose what we've noticed recently since Covid is trying to physically meet so that we're actually in the same place as much as possible, because we're finding that between collecting patient samples, working in the hospitals, working as teachers, which most of our PhD students do as well, just to fund themselves, we're never in same place. So I would actually have to say getting the community and meeting each other.

Even if your projects are completely diverse, it's really important as much as you can. And then I suppose just making sure that we schedule individual time. I used to meet everybody once a week. Now we're kind of they're more independent and they don't necessarily need that. So at least once every two weeks with everyone individually. And then we just share the group. And what happens in our lab is someone could be working on something completely epidemiological, but they'll know all about the basic science and back and forth. 

Nearly everyone is on everybody else's research. So I think that's really nice. And again, we have them because I'm chair of pediatrics and I teach pediatrics rather than just neonatology. We have people in our lab who doing allergy, neurology, endocrinology and so on. So it's a really nice mix. Of course, we try and always bring it back to neonatology in some form.

But yeah, and I think it's kind of really getting everybody together and socializing is very important. Because it is so easy to do Zoom, isn't it? And not meet.

David McCulley (11:51.129)

It is, but I agree the connection that you have with in-person meetings is so much greater and it's much easier to be able to, I think, make progress when you're sitting together rather than in virtual meetings, because it's so easy to be distracted. When you're talking by Zoom, there are so many other things that are going on. And when you're actually sitting face to face or as a group, you can see everybody's engaged and the connection is stronger. I think people's critical thinking is a little bit more focused when you're in that kind of a meeting instead. So yeah, that's good advice for sure.

Betsy Crouch (12:27.01)

We've started doing this. Is that OK, David? We've started to do this thing where when we get asked, when I get asked to review a paper, we've started to do a journal club on it where we usually meet in like in the afternoon. I bring snacks, as you were alluding to earlier, plus minus wine. And we sit and we read the paper like a journal club where each person has to go around and talk about each figure. And the engagement, as you were alluding to earlier, David, has been just phenomenal. And I think I feel enthusiastic about it because the review that I'm then providing is such high quality because I've actually had, you know, five people from my group take a look at it and different people pick up on different things. My technician, my lab manager, who's, you know, the most junior person in the lab, recently found basically some evidence from a paper that we were reviewing that could indicate research mixed conduct. It was him. It was like the most junior person in the lab who was just kind of Googling around the internet and found Elizabeth Bick's previous post on this group and then was concerned enough to look more carefully at the data that was being presented. And I thought like, because of this practice and this rigor, I feel like I'm doing a much better service for science. And I don't know, that was really exciting. as you're both talking about, it's because we sit in person and we have the manuscript in front of us and we spend like 60 to 90 minutes just looking at this manuscript with five to eight sets of eyes. So I think there is something that has become really precious about those in person interactions and the quality that sometimes is missed when we're all transactional and efficient, which there's a place for that too.

Eleanor Molloy (14:35.999)

Well, Betsy, think you've designed a new way of reviewing papers with wine and snacks that I really like because I think, as you know, in publishing, the hardest thing is to get people to review papers and doing in that fun way is really important. And then how can you change clinical practice if you can't read papers and you don't understand the science? So I think that's really cool. You have to kind of coin a phrase or call it something. The Crouch Review or something like that.

Eleanor Molloy (15:05.137)

We do like the shut up and write movement that we could do around the world. I do think that doing it in person is brilliant. And you're right, it is often I find the medical students you learn so much because they're looking at with a different lens and probably more detail and not glossing over the things I'm glossing over. So I think having everybody is really useful. And we also have our parent representatives because we are really lucky we've got Patient and Public Involvement (PPI) representation in our lab. Actually our PPI representative picks out things all the time for us and is on our papers. And so it's a really nice perspective. Now I'm going to have to bring wine and snacks for all future meetings if they hear this podcast.

Betsy Crouch (15:51.363)

Well, it's Dublin maybe. I had a lot of Guinness when I was there, which it's tastier in Ireland than it is in the US, I'll say.

Eleanor Molloy (16:04.484)

This is where I admit I'm not a Guinness drinker, but I hear the same.

David McCulley (16:10.917)

Eleanor, you said you have a parent representative in your research group. Can you talk about that a little bit more? I think that's something we haven't talked about in this podcast before.

Betsy Crouch (16:18.528)

I will say I'm leaving today to go to a meeting that's on a genetic condition that is run by a parent and a physician and it's all patients and families and clinicians and scientists at the same meeting. So I'm a huge fan of this. And I hadn't even thought about a parent representative in my lab. So please tell us what we're missing.

Eleanor Molloy (16:42.399)

I think in Europe as well, our granting bodies have insisted that you have family members and parent groups from the inception of the idea the whole way through and you have to show involvement. And so sometimes it always did in the past feel a little coarse if you go to somebody who you know and you say, can you help? You feel that it's not fair. So we have tried to go more through parent organizations. But we were really lucky when we had a PhD program to have someone who was our coordinator who happened to be a parent. And she has changed everything in our group about how we write, how we think. And then we have other parent organizations as well that we've been involved in. And of course, we were talking a little bit about necrotizing enterocolitis. And I think the NEC society is an incredible example. That meeting is wonderful. And Jen Canvasser, with having inspired everybody at that meeting.

Eleanor Molloy (17:38.464)

As a parent to start an organization like that which has been so successful. And at that meeting, at every session, a parent talks about their experience and it is, it just, brings everyone back to what's important. It's really nice. But I think that more and more families are involved across lots of our areas of research. So it's great. Again, you all, I do worry about taking too much time from people's lives when they're extra busy because they have a child who's been unwell. So that's why we try and have a parent organization. So then different people can substitute for each other. So you have someone in the group all the time. And then what we've done before with some of our PhD programs, which we try to do is always have someone from the parent organization who's matched with the PhD student. So they have their own kind of relationship to go more in depth into the project.

Eleanor Molloy (18:37.823)

You know, for example, if we had an EEG project or an MRI project, we'd have a parent completely focused on that from everything from consent to what's useful to doing infographics and so on. So it's really nice. And we have had interviews as well when we have parents there and they say why they're at the interview and everyone does have a little cry. I have to say it's very emotional, but it lets the interviewee then tell why they're what motivated them.

So sometimes they'll tell something personal about why they're motivated for the job in a way that you can't really ask in an interview. So I think it is wonderful to have that ability to have families involved.

David McCulley (19:19.631)

Yes, it's so inspiring. The stories are very emotional, as you said, but I feel a sense of connection and then also just the being motivated by what's motivated them, the questions that they think are important, being directly involved and having a very powerful story. It’s very compelling. And so then, I mean, we often talk about trying to attract people who are coming up into doing physician scientist work. And I think that is really helpful to be able to demonstrate it. Here we have this collaboration between this highly skilled researcher and also this parent advocate who has had a child with this disease and we want to know more about the underlying basis of it, or we have this question that we've worked on together. I think that's such a compelling model for being able to inspire the next generation of researchers, but also to just make progress generally. So that's outstanding. I have to say, in my research in CDH, we engage with families who have babies with CDH because we're collecting human samples. But for the most part, the things that we are working on, like how does this gene function in directing diaphragm development or lung development, I think the parents are often interested to know, can you identify an underlying cause or they are interested in the genetic mechanism. But the nitty gritty of how does this cell develop or things like that? I don't know. I'm sure they would be interested to know more about it. 

Betsy Crouch (21:10.424)

Well, I want to know what Eleanor has to say because that's exactly what was on my mind because I think we're evolving from the idea that we do research in parallel with families to the actual integration, which is what it sounds like Eleanor has envisioned well in the integration of somebody actually in the lab.

Betsy Crouch (21:36.911)

I'm curious if there's an example. I'm going to this meeting today on 16p deletion syndrome, and we have a grant from the California Institute of Regenerative Medicine to understand the metabolic implications of vascular cells in this condition. Franki Herrera, who's the woman who runs this organization, said metabolic implications of the disease can be a big factor in the lives of these individuals. So she said, I think you need to get perspective from the community on what it's going to mean to potentially intervene on metabolism in the setting of disease where metabolism is actually something that impacts their lives. I think that is a brilliant idea and truthfully something that we were thinking about already. There were a number of physicians and physician scientists amongst the group who were envisioning the grant.

But that's one of the goals of my presentation, is to ask the community, how do you feel about metabolic interventions for this disease? What are your concerns? What are your insights? And so I think we're moving to a place where the families and the implications of the disease, we're starting to get a fuller picture, I think, of potential hypotheses that will impact our experiments in the lab.

Eleanor, do you have examples of this?

Eleanor Molloy (23:04.383)

I think that's amazing. I again, I'm thinking of Betsy Pilon, who is in Hope for HIE and she is a huge parent advocate. And I think as well of Lily Collison and Cerebral Palsy Foundation, and they've just brought loads of energy, I think, to all the research. But they would be again, David, I feel, be very interested in basic science and mechanisms and what's going on. But I do find as well, we are kind of more inspired to do things like do clinical pathways in parallel. So even though we might be doing a lot of basic science in the lab, everyone does things like generating a definition. We did one recently of neonatal encephalopathy, or we do a practice guideline, or we look at what's the evidence for a change in clinical practice in a different area. So we would do them at the same time, which is nice for everyone who's a clinician anyway.

David McCulley (24:01.873)

Within your research group, you're doing that? I think that makes it so much more translational when you may have a very focused basic science interest, but you're also constantly thinking about how can we inform the clinicians who are working in the hospital? How does our work relate to that? And if it's broad, that's great. If it's very focused, that's also great. I just think that interaction, that constant interplay between basic researchers and clinicians is great. But also just the same type of critical thinking that you applied to a basic science project and then extrapolating that to developing a comprehensive guideline is very important as well. And then having the parent perspective on both of them I think is also really exciting.

Eleanor Molloy (24:50.144)

Yeah, because I'm lucky enough as well to work with Mandy Daly in Ireland and she's a parent representative who has written so many grants and been on so many papers that she's a wonderful advisor actually about how to write European grants because she's just become so involved. We are lucky that we have a large group to call on in different areas of research. So it's fantastic. And I think the big thing as well is just making sure that the parents are on the paper as well. Even if the paper is in an area, as you said, that might be very detailed, I think it's really important that they have a part in it. They've probably had to listen to us talking so much, but I think that's really important so that it's not like the scientists are doing one bit, that everybody's involved in every bit.

David McCulley (25:38.343)

Can you talk about just for a second longer? You said the granting agencies in Europe are really motivated to have parent engagement or family patient engagement, I guess, in research. And so in order to apply for funding, you need to have a patient representative as part of your application. Is that right or how does it work?

Eleanor Molloy (25:55.763)

Absolutely. We've had parents as co-applicants as well as collaborators. And then in previous projects, as I said, we'd actually always paired a parent into each PhD program or PhD project. So then it would be just showing evidence that at every single part of the research planning, execution and publication and dissemination, the families and parents are involved in that.

That would be a core part of every grant. And actually, our granting body in Ireland then gets every grant reviewed by a parent representative. So you'll have that perspective. And did you really explain it properly? So it might not be a family member in the same area that you write the grant in, but they might kind of question it. And so it is a very, very important part of the project.

I have to say the most stressful grant I ever wrote was one where all the parents wrote it and they wrote their segments. You know when you ask someone to say what is your contribution and they wrote about their own child and their own experience. And when I read the grant it was like my goodness this is the most amazing grant. And I said, what are we going to say if we don't get it. And we didn't think we were going to get the grant. So I think that's the only pressure is just saying to people's expectations that we might not get this.

Eleanor Molloy (27:19.508)

We try to do this in the journal as well, parent reflections and family reflections. More and more we're noticing people are including those in grant applications. You know, where we ask parents to reflect on what will be useful, say for example, in necrotizing enterocolitis, where does it need to lead? Try to have that perspective.

Betsy Crouch (27:51.203)

I really want to talk about biomarkers and neonatal encephalopathy or differences between boy and girl babies in Down syndrome. I think it was interesting, Eleanor, when you said.

David McCulley (28:31.143)

Can you talk about that just a little bit, Eleanor? It sounds like inflammation was something that was interesting to you. And then you talked about early on, you were interested in sex differences. Can you talk about that? It seemed like it focused on neonatal encephalopathy. So that seemed to be like where you were kind of interested to get started, but now it's expanded widely. So I'm just curious to hear a little bit about how you develop that interest and what are the things that you're trying to learn more about?

Eleanor Molloy (29:01.854)

I have to say, yes, my thesis was core based on neonatal encephalopathy, but then it did have to expand just because patient numbers, and it took me three years to recruit my patient numbers I needed for that. So I'm still really interested in neonatal encephalopathy, and that is a core thing. However, what I intend to do with the research is I do have to follow the money in the grants is part one that we all have to do. And then I also follow who our PhD students are and what their interests are in. So that does end up meaning that you go in slightly different directions. 

And then as neonatologists, of course, we're interested in all organs, which makes it a little bit harder to focus. I think that sometimes what we'll do is go with what the PhD student is interested in and then try to see how we can do multi-organ studies. 

Eleanor Molloy (30:27.22)

I suppose what I really like about inflammation is that it affects every organ and affects every baby. It is something we could modify and change. But I worry about trying to give medications to children without actually understanding what's happening in their inflammatory system. And I think there was a group talking about sepsis recently and we were saying how a lot of neonatal immunology is based on cord blood, which is completely different to actual babies. We want to rewrite the whole world of neonatal immunology. The other thing I like about it is that if you have an abnormal, dysregulated immune response at birth, it does seem to persist irrespective of whether you have NEC, you are born preterm, have neonatal encephalopathy, cerebral palsy, or Down syndrome. And when you check children later, and we're trying to do more adult work now as well, this seems to continue and may contribute to long-term issues.

Eleanor Molloy (31:24.352)

So what we'd like to do is see what interventions you can use. Then our ideas in the lab is that we will take blood from a baby and we might look at what's been done in animal models and then we will treat that blood. We'll try and stimulate it and see, can we decrease these abnormal inflammatory responses or augment them depending what the case may be in the lab and just see what doses work and then see, can you extrapolate that with animal models into clinical trials? So I think we feel that we're that human translational piece in between. And then I was saying it does depend on the PhD student and what area they're interested in. We do tend to adapt and because inflammation affects every organ and we're neonatologists, we like every organ. We try to put everything together and it is sometimes hard because we don't really have a home society for neonatology where everyone sits in the room and talks about inflammation inhibitors across lung and heart and kidneys. We're all a little bit separate silos, which is probably a necessity too. So I like inflammation because it mixes that all together. And we see similar patterns across different groups of patients. So going back to neonatal encephalopathy, that is nearly in some ways more straightforward because they all have a massive hyper inflammatory immune response. So you could envisage that you could use the same type of drugs and interventions in that group. Whereas I think with neonatal sepsis, our babies are dynamically changing so much that you have to be careful about giving, knowing where they are and what drugs would have to be tailored for them and individualizing it and personalizing it to that patient. So I think that's very interesting.

Betsy Crouch (33:06.624)

You mean at their developmental stage, Eleanor?

Eleanor Molloy (33:13.856)

I think tailoring and through childhood and not just, I know that we say, for example, in neonatal encephalopathy, we use therapeutic hypothermia as a baby and then we don't think about treatments later in childhood. But I think thinking about those treatments and then looking at all the other organs like, have you been checking their blood pressure throughout childhood? What's their kidney function like? How is everything else getting on? And I think that's something that we don't always think about all the organs.

David McCulley (33:41.655)

One thing that seems to translate through all of your work is just looking for differences between males and females and looking for differences at different gestational ages. And I was just wondering, I mean, aside from just demonstrating that males and females are different and biologically different and understanding that might help us to be able to treat them more effectively, how else are you thinking about it? Like, are you trying to understand mechanisms of disease that are unique to males and females? Or what is what's your thinking about that?

Eleanor Molloy (34:11.744)

I know it's a really good point, David, because when we do this, yes, first we're saying everyone's different, but then what can you do with that information? And I know in the past there's been some clinical trials where they've used estrogen analogues only in preterm baby girls, shown improvements in lung function and development, but in small studies. And again, you can't really give estrogen analogues to boys at the moment. So I suppose I'm kind of wondering, and this again more is epidemiology, is should we be using different doses of steroids in baby boys, especially twin baby boys? Should we be tailoring treatment more by sex because girls are probably making more estrogen and protecting themselves better. So I do think there's that element. And we found that in studies where we added estrogen and progesterone, we could change to blood, that is not babies. We could change their inflammatory profile. And we found this as well in adult human blood. You could make a male neutrophil, actually like a female neutrophil, if you treat it with estrogen. So I think there probably is a space for medications that don't have too much estrogenic effects, but have steroid effects that might be beneficial. So looking at boys and thinking about how we measure steroids, again, steroids are hard to measure, as you all know, but I think now with really good advances in mass spec techniques, we can probably measure it more accurately.

David McCulley (35:42.907)

I think that is just such an important point to highlight. I mean, this is a topic that's received a lot of attention recently in the US. And it's something that it's just important to demonstrate that there are important biological differences. And without understanding them, we're just losing many opportunities to be able to better treat patients. So I think it's just one thing to just keep focused on. How does doing this research impact our understanding of the mechanism of disease, but also why would one treatment that we use all the time potentially be risky in one subset of patients because of their biologic background, their sex?

Betsy Crouch (36:21.334)

I think it's so interesting moving from protocolization, which certainly is one way to improve our care, right? Is to make sure that everybody knows about certain quality metrics and that we have a standard way that we treat every baby. But I think the next stage is personalization beyond the protocolization. I think biomarkers are going to be an important part of that.

Betsy Crouch (36:50.966)

I wanted to follow up on a different scientific thread that you mentioned earlier, which is the fact that cord blood is not representative of the baby blood. Could you talk about that a little bit more? I think like everybody, we're interested in the immune cell effects on different organs, and our favorite organ is the brain. And so it would be helpful for me personally, and I'm sure for our listeners to hear more about the differences between cord blood and the baby's immune system.

Eleanor Molloy (37:22.072)

There's a lovely paper by Peter Brodin where he looked in absolute detail at cord blood and then neonatal blood all the way through childhood, looking at every different protein and immune function and just showed large differences. Cord blood is absolutely wonderful in research if you want a large volume of blood and you have to do a big experiment. But we find that you would have to give a lot of stimulation to the cord blood to get a response. So sometimes we actually have to make it hypoxic, we have to give endotoxin about three times and then it responds. And so I think that has been where everyone has always thought that babies don't have a very immature or abnormal immune response. So we got a big fright when we started doing neonatal controls from babies having blood for other reasons. We found they actually produce more cytokines than adults do and they respond really well to endotoxin stimulus and we were kind of worried our controls were wrong, but we noticed a lot of other people were finding this too. So I think that babies actually can respond really well, but they are adapted to not be rejected by their mother and vice versa when they're in utero. So they have a slightly altered immune response, but it's not that it's necessarily deficient. And I suppose that's why later on we see such an inflammatory response with necrotizing enterocolitis.

I also wonder about pulmonary hypertension as an immune response early on as well, that there's an element of that. Now David is the expert on this area, but I think there's lots of things that probably have an inflammatory element to them.

David McCulley (39:06.683)

I was just thinking, just because you talked about just how inflammation in the immune system affect all organs. And I was kind of then wondering, in addition to thinking about the patients as individuals and their immune system making them unique, I wondered if you have found instances where in one organ, if you modulate the immune system, you have one effect, but you might have the opposite impact on another organ? 

Pulmonary hypertension is a good example where, you know, sort of inducing a fetal program may have a poor outcome, but being able to preserve development, say in the brain or in another organ in a preterm infant that has an inflammatory reaction to NEC or sepsis may be beneficial because it allows for continued development. I don't know if you've found that or if you're thinking about that. It just seems like being able to target individual cells and different organs to modulate their immune response might be important.

Eleanor Molloy (40:13.822)

Now I think you're definitely getting more advanced than I am because I'm very simplistic and have an only work with blood, which probably goes to every organ. So I probably look more at just immune cells, but you brought up something really important David is about the immune system that nearly every cell in the body can respond in some immunological way. So it doesn't have to be just monocytes, neutrophils and lymphocytes, which is what I work with. So I do think that's really important, but very hard to measure in human beings.

But I do think more and more, especially when we think about necrotizing enterocolitis and the gut immune system is very really, important. But I don't know completely the answer to that, because I'm assuming that the blood where we're taking our samples, it goes to the entire body. And I suppose what's handy about that is you can see the cytokines in the systemic circulation and you know they're going to affect brain and kidneys and heart, protecting the babies against that storm. 

You've brought up another important thing is I suppose you have to modulate it because you can't just block it because then they're going to get sepsis and it's all going to be, it's not going to work out well. So how do you actually modulate the immune response and just get it to the exactly right level? We're calling it the Goldilocks zone. It has to be just right. How do you get there?

David McCulley (41:34.585)

I really love thinking about that. These things that are in biologic balance, you can't just think of it as an on or off. You have to think about it as tuning. And I think that's just another level of complexity is like, how do you find the appropriate tune? And also that it may be different from one cell in one organ and its neighbor, even in the same organ. So there are so many questions to ask. It's very interesting.

Eleanor Molloy (42:01.276)

Absolutely. And I think it's so dynamic that it might be different one hour later in the same baby. And I suppose because you study pulmonary hypertension, you see that all the time. That, you know, suddenly the therapy you're using, might be a bit too successful.

Betsy Crouch (42:20.46)

Yeah, and you know, on this topic, there's some emerging literature from Wendell Lim, who's a scientist at UCSF, where the idea is that you have immune cells that are synthetically engineered to be gated for a specific organ. So that the immune cells, when they enter a specific organ, then they encounter some endogenous antigen that then activates them to do a function that they otherwise are restricted or inhibited from doing. I like this topic a lot. And I think that we could learn and borrow from our cell engineering friends and colleagues in terms of how to activate the immune system, specifically in an organ targeted way. But yeah, that's a very exciting opportunity.

David McCulley (43:15.481)

One thing, Eleanor, we wanted to ask about was just that it seems like you have been incredibly successful in your ability to collaborate internationally. And to people, I don't know how Betsy has done it, but for me, it's challenging to collaborate internationally. I meet with people at meetings where, you know, we're working in different countries and it's interesting to be able to see like what you can do, say in Germany or in Great Britain or in other places. But it's difficult to actually get grants together and things like that. Can you talk about your international collaboration and things that have worked well and challenges that you see?

Eleanor Molloy (43:51.841)

I totally agree with you, David. I think it is really hard. What's handy is, I suppose, having worked in the journal, which is the official journal, say, for Society of Pediatric Research, European Society of Pediatric Research and American Pediatric Society. Therefore, we're always trying to see how can we get those societies to collaborate and write papers together. So I think and then in the European Society of Research, it's actually divided up into sections. So there will be a pulmonology section, a resuscitation section.

Eleanor Molloy (44:21.674)

We've got next special interest groups, we've got special groups on stem cells and so on. So what we often do is harness those groups to write papers and then get their international community involved. And then you're focused on writing a paper together or doing a task. Because I do agree with you, we can have lots of meetings and talk about things and sometimes getting grants together, you know, they're not successful and then that whole group falls apart.

Eleanor Molloy (44:48.32)

So it's trying to find tasks that you can do as a group or even going to a meeting like the NEC society together or things like that that you have to organize because otherwise the group does kind of lose momentum, I think. And I look at very successful groups in neonatology. think the neonatal kidney collaborative (NKC), the NEC society, of course, the American Thoracic Society (ATS) in cardiology and pulmonology. There are so many and Newborn Brain 

Society.

Eleanor Molloy (45:15.552)

They all kind of work on tasks together and have subcommittees and groups and I think that really helps. And then getting those groups together so that you can harness them to make networks probably is the easiest way to do it. And then you have to have someone with amazing energy like I'm thinking of Mohamed El-Dib in the Newborn Brain Society who made it all happen. And I think that's so sometimes I'll be sneaking and get into one of those groups so that we can do things together.

But I think writing grants across continents is challenging.

David McCulley (45:49.767)

I like your idea though, taking advantage of the achievable tasks. If you start with, we can write a paper together, we can write a summary or we can develop a guideline together. We can explore this topic together that we all have a shared interest in and publish something that's meaningful and it's going to be cited widely because we have people who have been really dedicated to this topic and they have important insight in the field. I think that is an achievable thing.

David McCulley (46:16.901)

And then it engages people to participate in a society. So you have achieved a goal, you've published a paper related to this topic, and then they want to come to your meeting again the next time you meet. And so then it becomes iterative. But I think it's that next level of how do you then build funding mechanisms or take advantage of funding mechanisms to keep it going? I think that's the thing, I don't know how to do that yet. 

Eleanor Molloy (46:44.096)

And I think I totally agree. I think that's a really difficult thing. I do think there's some sections in ESPR like pulmonology and resuscitation who've done that really successfully and where they've started doing maybe transnational questionnaires and working together on papers like that and then have developed these into doing international clinical trials together and have done them internationally. But maybe their basis was in these groups. And I suppose we're always trying to get the groups to cross the Atlantic and Pacific.

Eleanor Molloy (47:22.046)

So, of course, it is part of the publishing thing is we think the messages are more powerful if they come internationally. So we would be really encouraging that.

David McCulley (47:36.903)

So then let's go to that next, just your role in Pediatric Research. And you alluded to how you got involved in that through your connection with Cynthia Bearer. But just as a neonatal physician scientist and someone who is trying to foster the next generation of researchers very broadly, how do you see a role at Pediatric Research? What's exciting about it? Do you have any messages for our audience that you think would be interesting.

Eleanor Molloy (48:06.944)

Well, it is actually really fun because you get to see everything that people are writing. And then, for example, now, David and Betsy, I can email you and say, I'd really like you to write a paper on a certain topic and people might actually reply to you and do it. So that's really nice. And I go to meetings and we kind of go around looking for people we want to write papers for us. So that actually is really nice.

Eleanor Molloy (48:35.026)

And you kind of keep up to date with what's interesting, what's hot. Though Pediatric Research is across so many different specialties. I mean, I definitely am not an expert in endocrinology. So we're really looking with endocrine specialists and so on. So I do think for any young investigators, we have opportunities for young investigators, things like reviewing articles, getting your mentor to help you to do that. I mean, OK, this might be more tame than what Betsy described as a review process, which is more fun.

But reviewing articles is really important because it helps you understand how to write one yourself. And I think we also have opportunities like travel awards and so on. But then I would say just to be brave and go to your mentor and say, can I write something with you? And just to take every single opportunity to write something. 

What we've done is be brave when we did neonatal sepsis definitions. I went to all these famous people in pediatric and adult sepsis who I thought would definitely say no and surprisingly came on steering committees and so on. So I think it's about just what's the worst thing that can happen? They might just say no or they're too busy? But it's amazing how people will engage with you. So I would encourage people to literally go and ask. I definitely went to Richard Martin who was our mentor in Cleveland and just asked him. And he was brilliant and that really helped.

Eleanor Molloy (49:59.521)

So I suppose in the journal, I do think that, I'm going to say the boring thing, publish or perish. If you did that work, you've got to publish it. And then what's nice about having family engagement is you ask those parents to participate, and you got their consent, and you went through ethics. So I think when you don't write it up, I do feel it's kind of nearly ethically not fair on the families who are involved in the study. So I do think just and then it's how people can help you get through the last phases.

Eleanor Molloy (50:29.192)

Getting your group together and maybe having writing groups so someone else could finish it off. I think that's the hardest bit, isn't it? So I would just encourage people then, if you feel you've got your paper and you can't bear to look at it anymore, is to find someone else who'll do it for you. Just do that last push. I think everybody knows what that is.

David McCulley (50:51.705)

It's just interesting to hear how different people do it. I think everybody has a slightly different approach. I think even for the same person, it might vary from time instance to instance. But I think just that there's a community of researchers who are all doing the same general idea, but finding things to motivate them. And I love the point that you made about how having parent engagement helps you feel motivated to get over the finish line. Because sometimes you feel like it's just insurmountable. You're not going to be able to get it together. But that is, I could definitely see that that would make me want to get it published and just to feel like I, you know, to honor their participation.

Eleanor Molloy (51:32.744)

Yeah, I think you have to find any hooks that can make you feel guilty enough to get it published, because I think we all know it is quite a long journey of persistence. So I think it's anything that you can use, someone making you feel guilty, whether it's your PI, supervisor, colleague. And that's why sometimes having other people on your paper and having writing groups really helps.

David McCulley (52:00.775)

I agree.

Betsy Crouch (52:03.394)

Yeah, it is a long journey, but a rewarding one. As we're getting toward the end of our interview, we'd like to finish on something fun. So we've learned a lot about the activities that different groups do to bond or just to add some lightness to the intensity of our scientific investigations. Is there something that you and your lab group enjoy doing or a tradition that you would tell us about?

Eleanor Molloy (52:33.92)

I was asking them today in lab meeting what I was going to say for this question. And I knew it was coming and I said, and we have to sound like we're great fun, but we do, I suppose we do go out quite a lot and we celebrate a lot because most, when our fellows do leave after the PhD, you know, they're probably going to a different country to do a fellowship. So we would have a lot of get togethers and we do spend time together.

Eleanor Molloy (53:03.424)

We go for a hike every year and that's organized by our institute where we kind of all go with our dogs and other family members up a mountain which is lovely near in a beautiful place in Ireland. And then one of our post-docs has organized escape rooms and things like that. So we do try to do other activities together as much as we can. In the journal, we are obsessed with dogs. I have to have a disclosure there. So if anyone wants to send us papers about dogs and we would commonly. So our outlet is our kind of our family and our dogs and so on. But my only thing, I suppose, is how my work and life blend together. When I was going for my chair position, I would have been sitting outside football matches with my children. And I remember several nights as I was finishing presentations, loads of moms getting in the car with me and giving me career advice and changing my slides and doing things like that. So I think it's amazing how much support you can get from people looking and saying, I don't like that slide. It might be in a completely different area of work to you. So I think we do all bring our work to our fun and vice versa.

David McCulley (54:22.023)

Yeah, you can pick up good advice from anywhere it seems, and that's really good to take advantage of it. And also just good to hear because I feel like getting another person's perspective on what you're talking about or trying to learn about and then present, if you can convey it to them and it's not their field at all, I feel like you can get so much good insight and just do a better job of talking about your work. So that's great. Good example.

Eleanor Molloy (54:40.457)

Absolutely.

Betsy Crouch (54:46.414)

This is very California, but one of my PhD students, Cassie, told me how she was networking as she's surfing recently. And I thought, well, that's a good one. But you know, very California. In Ireland, you take hikes with your dogs. And in California, I imagine she's like on her board and riding a wave and talking to the person. She says, I keep meeting all these scientists in the water. Well, it's productive. So good for you.

Eleanor Molloy (54:46.718)

absolutely.

Eleanor Molloy (55:17.76)

So that is definitely the coolest collaboration method that I've heard.

Betsy Crouch (55:21.646)

Okay, well, yeah, the surfing, the surfing collaboration. So we'll start the new neonatology surfing society. There we go. We have ended this interview on the peak of inspiration.

David McCulley (55:39.633)

Perfect. Thank you so much, Eleanor. Yeah, that was outstanding. Really fantastic to talk with you. Thank you for taking the time.

Betsy Crouch (01:05:15.182)

Thank you, Professor Molloy for a wild Irish ride. For really, I think, showing us a different way, a broader way, a more international way to think about the differences that we can make as neonatal physician scientists. So this has been a delight and really thought provoking. Thank you for joining us today.

Eleanor Molloy (01:05:42.324)

Thank you both, that was wonderful.

David McCulley (01:05:44.519)

Perfect, thank you so much.