Hello Friends 👋

In this episode of the Incubator, hosts Betsy Crouch and David McCulley welcome Dr. Judy Aschner, a prominent neonatologist and physician scientist. Dr. Aschner shares her journey building a research career and emphasizes the importance of mentorship, determination, and collaboration across disciplines. She discusses her personal experiences that shaped her research focus, particularly in pulmonary hypertension and environmental health in neonatology. The conversation highlights the challenges and triumphs of a career in medical research, underscoring the significance of intellectual curiosity and the impact of personal experiences on professional paths. Dr. Judy Aschner discusses her groundbreaking research on manganese levels in parenteral nutrition and its uptake into the brain of infants with prolonged exposure to TPN. She highlights the importance of understanding metal environmental exposures in the NICU and the collaborative efforts that led to successful grant writing for research projects. Dr. Aschner emphasizes the need for inclusivity in research, particularly for children with disabilities, and the significance of longitudinal studies in assessing long-term health outcomes. Additionally, she shares her passion for rock climbing as a means of maintaining mental and physical health amidst her demanding career.

----

Some featured manuscripts from Dr. Aschner:

Logan JW, Tang X, Greenberg RG, Smith B, Jacobson L, Blackwell CK, Hudak M, Aschner JL, Lester B, O'Shea TM; Program Collaborators for Environmental Influences on Child Health Outcomes. Neonatal Morbidities, Neurodevelopmental Impairments, and Positive Health among Children Surviving Birth before 32 Weeks of Gestation. J Pediatr. 2024 Oct 30;277:114376. doi: 10.1016/j.jpeds.2024.114376. Epub ahead of print. PMID: 39481800.

Stroustrup A, Zhang X, Spear E, Bandyopadhyay S, Narasimhan S, Meher AK, Choi J, Qi G, Poindexter BB, Teitelbaum SL, Andra SS, Gennings C, Aschner JL. Phthalate exposure in the neonatal intensive care unit is associated with development of bronchopulmonary dysplasia. Environ Int. 2023 Aug;178:108117. doi: 10.1016/j.envint.2023.108117. Epub 2023 Jul 26. PMID: 37517179; PMCID: PMC10581357.

Aschner JL, Anderson A, Slaughter JC, Aschner M, Steele S, Beller A, Mouvery A, Furlong HM, Maitre NL. Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition. Am J Clin Nutr. 2015 Dec;102(6):1482-9. doi: 10.3945/ajcn.115.116285. Epub 2015 Nov 11. PMID: 26561627; PMCID: PMC4658463.

Fike CD, Dikalova A, Kaplowitz MR, Cunningham G, Summar M, Aschner JL. Rescue Treatment with L-Citrulline Inhibits Hypoxia-Induced Pulmonary Hypertension in Newborn Pigs. Am J Respir Cell Mol Biol. 2015 Aug;53(2):255-64. doi: 10.1165/rcmb.2014-0351OC. PMID: 25536367; PMCID: PMC4566047.

Erez A, Nagamani SC, Shchelochkov OA, Premkumar MH, Campeau PM, Chen Y, Garg HK, Li L, Mian A, Bertin TK, Black JO, Zeng H, Tang Y, Reddy AK, Summar M, O'Brien WE, Harrison DG, Mitch WE, Marini JC, Aschner JL, Bryan NS, Lee B. Requirement of argininosuccinate lyase for systemic nitric oxide production. Nat Med. 2011 Nov 13;17(12):1619-26. doi: 10.1038/nm.2544. PMID: 22081021; PMCID: PMC3348956.

----

----

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

David (00:02)

Hello and welcome back to the incubator at the bench where we are incubating discoveries. My name is David McCulley and I'm a physician scientist and neonatologist here at the University of California in San Diego and Rady Children's Hospital. And I'm very excited to be co-hosting this program along with my co-host Betsy Crouch. Betsy, do you mind introducing yourself and introducing our guest for today?

Betsy Crouch (00:25)

Thanks David, yes, my pleasure. I'm Betsy Crouch. I'm a neonatologist, a vascular biologist and a neuroscientist at University of California, San Francisco. Yeah, we're kind of closing out a year of these at the bench incubator podcasts and planning for what's to come in 2025. And I could not be more thrilled today to have Dr. Judy Aschner as our guest. Many of you will know Dr. Aschner.

But I'll say that personally, I was able to be mentored her through the PSDP program. We had an annual meeting as a part of that program, and there was one meeting in particular where Dr. Aschner shared a wealth of wisdom with me that is still percolating in my brain like five years later. And so I was thrilled when she agreed to be on this podcast so that we could share some of her knowledge, wisdom with all of you.

For those of you who may not be familiar with Dr. Aschner, she is the former physician-in-chief and chair of pediatrics at both Hackensack University Medical Center and then also was the chair at Albert Einstein and Montefiore Medical Center. She has a tremendous body of work looking at the premature lungs and now has transitioned into this really impactful space looking at environmental exposures in our premature infants.

So that's just the tip of the iceberg. Thank you again, Dr. Aschner, for being with us. And if you could provide a little bit more introduction, I think that would be wonderful.

Judy Aschner (02:00)

Thank you for that. And I'm really thrilled to be here with you. Thank you for inviting me. I think this will be a lot of fun. So, I have had a really long career now that is taking me in directions I never dreamed I would go in when I first started out. So like both of you, I am a neonatologist and a physician scientist, although these days I have to flip that order. I'm more a physician scientist than a neonatologist these days. And I started my career out at the University of Rochester back in the 80s, where I did medical school, residency, and fellowship. And in some ways, went kicking and screaming to the bench. It was mandatory that the fellows back then do basic science research. It was the only option.

Judy Aschner (02:55)

I didn't have a background in any research. I wasn't sure that this was going to be for me. And I was told, just go do something, publish a paper, and we'll leave you alone. And to my utter surprise, I really liked it. And then when I left Rochester, I was there for more than a decade, I moved back to my hometown.

By that time, I had three children and then had a fourth. I grew up near Albany and I joined the faculty at Albany Med to be back near family and started working with Dr. Asrar Malik, a PhD vascular biologist, lung biologist, who really was the first true mentor I had, who believed in me and thought I could actually do research.

And while I was in Albany, I began to ask everybody I could find who I knew was smarter than me, why alkalosis causes vasodilation in the lung but constricts every other vascular bed and acidosis does the opposite. It was a clinical question, driven by the clinical care we were giving. Don't forget, this was the late 1980s, we were still hyperventilating those poor babies' lungs. There was no inhaled nitric oxide. What we did . . . ! I remember putting 17 chest tubes in the same child. It was a different era. But I was really interested in the unique signaling mechanisms of pH on vascular tone in various organ beds.

Judy Aschner (04:46)

And I started to reach out to other PhDs who weren't studying pH, but had tools that I thought they could teach me and that then I could apply to my question about vascular regulation and acid-based status. And that's really how my research career began. And then I had an opportunity to move to Wake Forest. . . 

Betsy Crouch (05:14)

Could we pause there? There are already so many, so many exciting things about your story. I thought it was so powerful what you said, the first mentor who believed in me. And I think mentorship as physician scientists is something that we are trying to promote, but also kind of interested in discussing best practices. So do you mind giving a little bit more color to what exactly the mentor did that was so important.

Judy Aschner (05:45)

Yeah, it's a little colorful too. You know, honestly, when I started my fellowship in neonatology, I knew I loved clinical neonatology. I was actually pretty good at it. And I loved taking care of the babies, working with the families. I thought it was just this incredible privilege to be able to be there at some of the most poignant and challenging points in people's lives.

Judy Aschner (06:15)

And so for me, I started my fellowship thinking I was just going to be the best possible clinical neonatologist there was. And I was actually told by senior people where I trained that my job was to keep those babies in the NICU alive while the other fellow got support and mentorship. People felt he had the background to become a famous physician scientist. He had come from the NIH, had spent six years doing bench research, was a molecular biologist in the days when molecular biology was just really starting. And I was told that nobody had any expectations for me to have a successful academic career. I was going to be a really good clinician and my job was to take care of those babies. And I got told that over and over again during my training to the point where I went, how dare you tell me I can't do this? And know, and I'm one of those people, the more you tell me that I can't do something, more likely it is that I'm going to really try hard. And so, you know, I left that training program really determined to make a go at research.

Judy Aschner (07:42)

Maybe I was trying to prove something to myself, to someone else, but the more opportunity I had to be at the bench and the more opportunity I had to interact mostly with PhD scientists, I did not have good MD scientist mentorship early in my career. The more I loved it, the more interesting it became. And honestly, as medicine became more prescribed and less creative, the bench was the creative output, right? One couldn't be crazy at the bedside anymore. I mean, I would do all kinds of things to try to save babies' lives with approaches to ventilation and other types of management that today, it's very protocolized. You don't practice like that anymore.

Judy Aschner (08:34)

And as I saw that transition happening in clinical medicine, I realized what a great fit science and clinical medicine is. And I also realized that although I didn't have formal training at the bench, I had clinical questions that the basic scientists didn't even know were important questions to ask. And that if I got into a team of people who would teach me how to do things at the bench, who would share with me their expertise, who would critique my approach to what I knew was an important clinical question, that that combination was really powerful. And so I've always been part of a research team. I recognize what my strengths are, but I recognize what my limitations are. And collaborating with people that have different types of strengths has really been a great approach for me. 

David (09:32)

Can ask you just a question about that? Just because I think you touched on three aspects that I think are really important for people to recognize. One is the determination. I think that you hit on that right away. And I think that is something that we have to perceive in ourselves, but also other people need to be able to recognize that is something that we are really passionate about, that we are always going want to strive to make science part of our career. Another is that intellectual curiosity that you recognize you had clinical questions that we can't easily answer in a clinical experiment or using tools that are right at our fingertips in the NICU. And then the third one is to seek out collaborators who are outside our immediate field. I think a lot of us, especially in training, are looking for mentors and potential collaborators that are right in our world every day in the NICU. But I really think we have to, as you said, in order to explore our intellectual curiosity and really build and think creatively, try to collaborate with people well outside of our little world. And it's through that type of collaboration that we really make new progress. And I wondered, how did you get the idea to seek out PhD scientists who could help you answer the questions you were interested in?

Judy Aschner (11:00)

First of all, there was nobody in the clinical division that really was in a position to help mentor me in the direction that I wanted to go. And I was very fortunate. Dr. Malik really supported me, helped me get a Parker B. Francis Foundation grant, and then American Heart Association grant. Introduced me to other PhD scientists, incorporated me into the laboratory program really in a way that made me feel like I was as much his mentee as his postdoc. He was really tough and spared no criticism. You got ripped apart in those lab meetings, but was really, really good for me to be able to do that. And then I was just lucky to find people who had tools and techniques and who were patient and thought my question was interesting and were willing to train me to do things that I then took with me as my career progressed.

Betsy Crouch (12:10)

My favorite thing that you said was how the bench is the creative output.

Judy Aschner (12:16)

And you asked about going to other fields. I can remember going to large meetings, FASEB, back in those days. I went to listen to the cancer researchers. My viewpoint, they were the people that were the furthest ahead in vascular biology.

And I would come back from those meetings with pages and pages of notes that I had taken listening to people in a completely other field. Trying to figure out how what they learned about, know, vasculogenesis for tumors might be applicable in the neonatal lung. And so I really encourage people starting out to think much more broadly about the fields in which you can really learn things and then apply in a different way to the questions that are burning that you want to answer.

Betsy Crouch (13:16)

I got the advice one time that you should read both broadly and deeply, but more broadly than deeply, more frequently broadly than deeply, because I think it opens up new possibilities. And then you need, there are periods of time, of course, where we're all writing that paper, that grant where you read really deeply. But I enjoy that because I guess I'd be curious how you all approach the literature. But my goal is to spend 30 minutes every day reading the literature.

Judy Aschner (13:49)

I get bombarded. have to say I get behind these days. I have a hard time just keeping up with the ECHO publications that I'm a co-author on.

David (14:02)

You were talking about studying pH and its effects on vascular tone and things like that. I'm just curious how you then kept building, like what was the next iteration?

Judy Aschner (14:21)

Yeah, so I got this American Heart Association grant when I was still in Albany. And then I transitioned to North Carolina and I was on the faculty at Wake Forest for 10 years. I brought that grant with me, got enough preliminary data to say, okay, I'm 10 - 11 years out of fellowship. I'm gonna write my first NIH grant. So I was a really late bloomer.

And I went to my chair and I said, you know, I'm going to write this R29. That was the mechanism back then. And he said, no, you're not. You're just going to write an R01. I was like, what are you talking about? So, he wanted the indirect costs. And so I found another PhD scientist who did cerebral vascular research in a neonatal piglet model, it was a really good match for me to learn more new techniques and bring it back to the lung. And I finally had to call the NIH and say, am I too old to run my first NIH grant? And they really encouraged me. There was no age discrimination at the NIH and to go for it. And so my first...

Betsy Crouch (15:42)

I'm sure you are all of like 35.

Judy Aschner (15:46)

You know, I had really seen so many of my contemporaries who were on the physician scientist track from fellowship, some of whom had PhD training and some of whom did not, hit the door running after fellowship writing, you know, an R29 or other, you know, types of grants. And I was worried that too much time had gone by. It felt like it taken me a long time. But as I said to David before we started recording, by that time I had four children. And I think had I actually tried and succeeded in getting my first NIH grant right out of fellowship, I might not have succeeded. Life was pretty busy. I was a full-time clinician. It wasn't a huge department, so was on call all the time. I was the fellowship director, and I had four young kids. And it was really when my youngest, right, started kindergarten that I went, I'm going to write a grant. That was when I thought maybe I can actually do this.

Judy Aschner (17:08)

And so it was sort of late compared to many of my contemporaries back then. But maybe it was the right time for me. Because that was when really I felt like I could devote more time and energy to it. And then having successfully gotten that grant funded, it was the heyday of the NIH. Pay lines were really good. It was my first NIH grant and the only one funded on its very first submission.

Judy Aschner (17:36)

that I was really given protected time. And I think that's one of the most important factors was my chair, who was thrilled that I had gotten this R01, gave me the time that I needed to do the work at the bench. And I think that was a really critical thing. And then after 10 years at Wake Forest,

I got recruited to be chief of neonatology at Vanderbilt. That was a pinch me moment. I felt like an imposter. It was like, are you kidding me? But I had already gotten another, our grant funded and you know, my daughter had already started medical school at Vanderbilt by then. So she was like, watch you're following me here. 

And she, by the way,is an NIH-funded physician scientist. I have to throw that in there. Very proud of her. And a Parker B. Francis Fellow. We are the first mother-daughter pair to ever be Parker B. Francis Fellows. They made a big deal of it the year she became a Fellow at Parker B. Francis Foundation. And she's an adult pulmonary critical care doc and does IPF research. So a little aside there. I'm really proud of her.

David (18:35)

Wow, that's great.

Betsy Crouch (18:58)

That's wonderful. I think it is the personal aspects of this job I think sometimes get lost, but there are deeply meaningful personal aspects to this job. Yeah, my kids are younger, but it's fun to see them start to put two and two together too based on the conversations that they hear coming out of my mouth all the time.

David (18:59)

It is good.

Judy Aschner (19:12)

It's true.

And you are going to hear about one of my other children in a minute, because it's very much a part of my story. So I got recruited to Vandy to be chief of neonatology. What a wonderful decade that was. You recently interviewed Erin Pelosa. She was one of my mentees, and I recruited Erin, both as fellow and faculty at Vanderbilt. And it was a blast. And I think that is really the decade where my career most took

Judy Aschner (19:50)

both my bench research in collaboration with Candice Fike, who's been really my long-time collaborator, going back to Wake Forest. I recruited Candice from Wake Forest to join me at Vandy about a year after I got there. And we have very similar research focus and interests, but very complimentary skills and techniques. And together we really do things that I think neither one of us would do as well alone. And it's been many decades long collaboration now. And I still have a phone call with Candice every two weeks since, you we've moved to different institutions, but we still collaborate together and are actually writing another grant right now together. So, so that was great. Those 10 years at Vandy were amazing. Learned a lot and began to get much more involved in translational research, including the environmental health research, which we can talk about in a minute. But I want to go back to the things that drive you to answer questions. So, I was really curious about the acid-based status and the lung mechanisms that cause the lung to respond completely differently than any other vascular bed 2-PH. And that really took me down a path into a chaperone protein called HSP90. And really from 15 years, my research focused on this chaperone protein and its role in nitric oxide synthase uncoupling. And really led to an entire body of research looking at the urea cycle and the enzymes, ASS and ASL and nitric oxide synthase, as client proteins for HSP90. And that with the right substrate, sufficient arginine, one has coupled NOS that produces nitric oxide. But a variety of things will uncouple that relationship between HSP90 and its various client proteins, including chronic hypoxia resulting in uncoupled nitric oxide synthase in the production of superoxide. And that really was the focus of the work that Candice and I did together, collaborations with Bernard Thibault in Canada, several animal models showing that not arginine, but citrulline, which is a precursor in that pathway, really drives endogenous arginine production in a way that exogenous arginine does not. This allows NOS to be coupled and to produce it as nitric oxide. And we had a variety of animal models, a Candace's Piglet model of chronic hypoxia-induced pulmonary hypertension and a rat model that I worked on with Bernard showing that citrulline not only prevents the BPD morphology of the lung, but prevents the pulmonary hypertension and right heart hypertrophy that's associated with that. And then an RFA came out for PROP, Prematurity Respiratory Outcomes Program, I decided to go for it. It was a wonderful opportunity to collaborate with a geneticist at Vanderbilt, Marshall Sommer, and a pulmonologist at Vanderbilt, Paul Moore. And the three of us were an incredible complementary team and wrote a PROP grant that got funded and really helped me take some of the work that I was doing at the bench and translate it into a more translational program that was very patient oriented, but still focused on this pathway that I've been studying for 15 years. And so that was a huge amount of fun. And in many respects, ultimately led to my current research in ECHO. But I want to go back for a minute and tell you about the next grant that I wrote after the grant looking at pH.

David (24:13)

Can I ask you one follow-up question before you go to there? I'm just curious because you and I were talking about this before we started recording how as in a career, you have this narrative that can sound very linear and intentional and incredibly productive and successful, which yours has been and does appear to be incredible. So I'm just curious because you have these really interesting models that you were describing with Dr. Fike and Dr. Thibault. And how did you see this as a way to demonstrate that through multiple iterative or overlapping experiments, you could really understand this pathway in detail? Or how did you really see it? I mean, were you seeing it kind of come together in pieces, or was it a part of a big picture the whole time? Or how did you see that you could develop it by adding this new model and then go to a translational model like you're, sounds like you're about to describe.

Judy Aschner (25:14)

Yeah, every step of it was a surprise. I have to say that, you know, from step A to step B, every time, you know, this idea would percolate and we would begin to talk about it. And then we'd get really excited about it. And I mean, I wrote half my grants sitting in a Starbucks in Nashville with Candace, right? Drinking endless coffee and just throwing ideas across the table and sometimes Marshall would come join us on Marshall Summer and as we would, you know, talk about where this could lead. We'd get so excited. We'd be sitting there, know, jotting things down, but each time we would submit that grant and it would get funded, we would be like, my goodness, this really happened. my goodness, now I really got to do this work, right?

Betsy Crouch (26:07)

Yeah, then there's that moment.

Judy Aschner (26:09)

I can't say that this was a linear path that I ever saw coming. And this huge move from the bench, because I no longer do bench research, to a clinical translational research program was a very slow trajectory. I mean, it took me a long time to give up my bench research. It wasn't until I moved to New York and became a chair that I realized this wasn't going to continue to happen.

But for a while I was still working with Candice at the bench, reviewing all of the laboratory work that was coming out of there. And then over time, my own grants became completely translational in nature and patient focused. And I was so thrilled to have a career that allowed me to learn all of the things that I learned.

Maybe some of the most important lessons being don't trust everything you read in the literature or 20 different ways that you can interpret that same data set and what was driving the interpretation of that paper that got published. Once you work with your own data set, you realize how much largesse you have and how it's analyzed and interpreted, completely using every little bit of data. But you come to these questions with the particular focus and then, you know, sometimes it doesn't work out but something more interesting comes out of it. The HSP 90 story was really like that from one step to the next to the next. And we published so many papers on this chaperone protein that, you know, I never saw coming when we first started this work. But to be able to take what you've learned at the bench, not just scientifically, but honestly as an intellectual approach to asking questions and apply it to your patients. Man, that's one of the greatest feelings ever. And I am so happy with the work that I am able to do now. And I realize I've been really lucky. I've been really lucky to have great collaborators. I've been really lucky that someone at the age like the work that we were submitting.

And then when I think back about it, I've been continuously funded by the NIH since 1998.

David (28:36)

awesome.

Judy Aschner (28:37)

But I did have a story I really wanted to share. And that is why I got so passionate about studying pulmonary hypertension. It started out as an interest in PPHN, but that quickly transitioned to pulmonary hypertension associated with all sorts of neonatal lung diseases. And a lot of that was driven by my own child.

So I told you I have four children. My third, not my last, my third child. I ruptured membranes at 21 weeks of gestation. Most horrifying personal experience one can possibly imagine, especially as a neonatologist, I knew what was coming. I was actually told to terminate the pregnancy and get back to the bench where I belong. That was actually said to me by a mentor.

If you had asked me what I would do the day before I ruptured membranes at 21 and zero, I probably would have said nothing to do, terminate the pregnancy before I get septic, something, know, nothing good is going to happen. But when it actually happened to me, I couldn't do it. I feel that baby kicking every day and decided whatever the outcome, this pregnancy was just going to take its natural course.

Judy Aschner (30:08)

And I went 10 weeks at bed rest, bed rest was quite the challenge for me, and delivered incredibly ill newborn, whom nobody thought was going survive the first 10 days of life, who had probably pulmonary hypoplasia, pulmonary hypertension, and somehow or other, not only survived, but today is thriving. He's a lawyer, he's a dad, he's fine. I don't know how he got so lucky. But that experience really changed how I practice neonatology and how I think about the importance of research and the need to understand, what is happening in the neonatal lung so that we can come up with novel therapies to improve outcomes for kids.

David (30:40)

Wow.

Judy Aschner (31:02)

And that has never left me and that personal experience has continued to drive my career.

So, yeah.

Betsy Crouch (31:13)

That's beautiful.

David (31:14)

Yeah, thank you for sharing that incredibly motivating story.

Judy Aschner (31:20)

And then environmental health was really also a bit of an accident.

I was always sort of involved with environmental health. I was married for 37 years to an incredible environmental health researcher whose first language was not English and had me read every grant and every paper he ever wrote. He's prolific. He has about a thousand publications now. I had no time to do my own research for a while, but I learned a ton.

I learned a ton about how to write good grants. I learned a ton about environmental health. It was all a big plus for me. And I became interested in NICU environmental health and wrote a grant to NIHS and the Gerber Foundation to study manganese exposure in the NICU, particularly in children on TPN.

Judy Aschner (32:23)

It was a little bit of an offshoot. It was not my major research focus back then, but I was really, really curious about this and decided to write a grant and lo and behold, it got funded and you know, what? So it turns out that there is a ton of manganese in parental nutrition. 

Betsy Crouch (32:35)

And what sparked that topic? Why manganese?

Judy Aschner (32:53)

Through a collaboration I had with Mickey at the time, we were looking at manganese levels in TPN and in infant's blood and infant's urine and realizing, my goodness, what are we doing? Nobody, there was no data published on this. The levels we were measuring in some of these kids were astronomical, like scary. And I actually remember I called the company that makes parental nutrition and said, you know, why are we using this formulation? And, and they just didn't want to talk to me. Like they had FDA approval for what they had. you know, they were like, you know, if you think this is causing harm, Dr. Aschner, you're have to go prove it. And I hung up the phone and went, yeah, you're right. I'm going have to go prove it. And I, and we, did MRIs on children who were on prolonged parenteral nutrition in the NICU. So kids with short gut syndrome, all sorts of GI problems to be in the study you had to have been on parenteral nutrition for like a month, right? And it turns out manganese is paramagnetic. And it is taken up on cells by the same transporter systems that take up iron and actually displaces iron in the brain - competes with iron. And we were able to demonstrate using MRI that manganese lit up the brains of these babies on prolonged parental nutrition. So that paper was published a long time ago. And in some ways, it then led to my first echo grant proposing to look at metals in the NICU environment among former preterm infants, both children who we had collected urine in on while they were in the NICU in prop, and then baby-suede urine samples from other cohorts that I included in my first echo grant. And we just got data back. It's not fully analyzed yet. Looking at metals in deciduous teeth.

So these were all babies born pretty much less than, most of them less than 29 weeks of gestation, who at age six and seven, you know, lost their baby teeth, sent them to us. And we're able to use a laser technique, not me, I don't do this work at the bench, but the Sinai lab that does this work, we're able to look at the levels of like the whole periodic table just about of metals in the teeth of these babies.

Judy Aschner (35:44)

Teeth are like tree trunks with rings that show you various ages and stages. And there's a birth ring that's very distinct. So you can look at a tooth and see the moment of birth. And down to a few days, clearly a week or less, you can look at the metal deposition in that tooth, both prenatally and postnatally and look at exposures. And so we're really excited, finally, to have these data. was a long time in coming and are visibly working. Yeah, we're waiting for teeth. Exactly. And really looking forward to publishing that work, which I think will be really interesting.

Betsy Crouch (36:17)

You were waiting for teeth? Do you need control teeth? My children have control teeth that I've, that I can't decide what to do with. Anyway.

Judy Aschner (36:34)

So we actually in ECHO do have control teeth. ECHO did collect deciduous teeth across all the birth cohorts and the pediatric cohorts and most of those kids of course are not preterm. Turns out the tooth analysis for the preterm babies was really challenging for that lab. They had to develop all new technology to be able to do it. The same with phthalates. You know, we had thousands of urine samples from babies in the NICU.

Judy Aschner (37:02)

Exposed to our chemically intensive environment in the NICU and there are phthalates everywhere, right? And, you know, phthalates are plasticizers that keep plastics flexible, strong, resilient.

Judy Aschner (37:25)

They're part of every plastic device we use in our NICU, our ventilator circuits, our nasal cannulas, our CPAP circuits, our in-z tubes, our IV tubing, where we give blood transfusions full of other toxic things. And so these babies are highly exposed and we were able to measure very high levels of phthalates in the urine of NICU babies.

Judy Aschner (37:54)

And are now looking at both short and long-term NICU outcomes. And with the ECHO program, you know, the original cohort that I wrote for ECHO for all former preterm infants, the DINE study, those kids are now almost teenagers, and we'll follow them to age 22. So we'll be able to look at all kinds of outcomes as a function of the phthalate exposures they had in the NICU.

And postnatally with all sorts of confounders. We need really good biostatisticians to do this kind of work as part of our our ECHO proposal.

Betsy Crouch (38:37)

Yeah, what a phenomenal idea. 

David (38:48)

Yeah, that's what I was thinking. Just like, in addition to the other skills you have, like you're also demonstrating like an incredible ability to teach. I've been taking a lot of notes while you've been talking. And I think that is really helpful because it is. Well.

Betsy Crouch (38:57)

Yeah, me too. This is Grand Rounds with Dr. Aschner here on at the bench this morning.

Judy Aschner (39:04)

But it's not linear. My thought processes are not linear. I don't know if that's all that you care.

Betsy Crouch (39:07)

That's what makes it entertaining, yes. Thank God for being a podcast.

David (39:11)

Well, you're taking a skill set that you learned to study one thing, pulmonary hypertension, as we were starting to talk about. And now you said you've translated it into a completely different question that is potentially even bigger, a bigger number of patients, all preterm infants or other patients who are exposed to TPN for a long period of time. And you're applying the same type of hypothesis generating and motivating research to try to be able to understand like what is going on. What is the potential impact of this exposure and how does it affect someone over their whole lifetime? 

But I was just curious because as you started to develop this interest, and I imagine your ability to teach about this topic and its importance was really helpful, in finding collaborators who would help you learn about tooth development and exposures and how you could study them. But can you talk a little bit like as you were trying to understand this question. How did you start to find collaborators that were going to help you be able to answer these questions and then build this really successful program that you have now?

Judy Aschner (40:15)

Yeah, so I do love to teach. I had either just published or had given a presentation probably at the PAS meeting about our data on manganese and the TPN and the brain MRIs on those babies. And I met one of my strongest collaborators now, who at the time was very junior in her career, Anne Marie Stroustrup. So Anne Marie was at Sinai. She was an environmental health scientist, neonatologist, and she was writing a K award really to look at phthalates and other NICU environmental exposures in preterm infants.

And she wrote to me at Vanderbilt and said, would you be willing to be one of my K mentors? And I hardly knew her at the time, but I was like, not only would I be willing, but I'm moving to New York. I can come to your K-meetings in person. I'm on my way. So we began to collaborate a bit, but mostly I was just her K mentor as her K got funded and she began to do this work. And then the ECHO RFA came out. And I saw it. And I picked up the phone and I called Anne-Marie and I said, this grant was written for you. And, you know, we talked about it and realized that to pull together a cohort and have credibility as someone who could lead a multi-site, you know, clinical translational longitudinal study. You know, she was a K-awardee very early in her career. And so I teamed up with Anne Marie and Susan Teitelbaum, who is a PhD environmental epidemiologist. And we wrote the first ECHO grant. And I have to say most of the preliminary data other than the metal data that was mine was Anne Marie's from her K-award.

And we wrote this ECHO grant into our utter amazement. It got funded. Remember getting the score and going, no, no, we're going to fund this. This isn't a good enough score. that's too bad. I really like this grant. And then I get a call like, I don't know, two days before the grant was supposed to start. I'd gotten no notice of grant award from the NIH saying, we would like to talk to you. I was like, OK.

So, I get on the phone with two people from the NIH and they start peppering me about questions about our grant, all sorts of questions. And when I, they told me it was gonna be a 20-minute conversation, it was an hour. And at the end, just before we hung up, she said, Dr. Aschner, wanna tell you, this was the scariest grant I have ever read. They were horrified by the background data we had.

Judy Aschner (43:20)

In there about NICU exposures and how nobody knows what the outcomes are, but here's our preliminary data and this doesn't sound like it's a good thing for our babies. And then, you know, two days later I got my notice of grant award and we were off to the races. And then, you know, Anne-Marie grew up through this ECHO program. She would be a great person to interview, by the way. She's fabulous, right? And we had a lot of success with PROP in ECHO. We transitioned from UG3 to UH3, not PROP with ECHO, and the DINE study. We transitioned from UG3 to UH3. And then when it was time for those seven years to be up and a new ECHO RFA came out, I had agreed with Anne-Marie several years ago. She was now chief of neonatology at Northwell. She would be the contact PI and I would be MPI on the DINE renewal to follow those preterm infants from cycle one into cycle two. And she did a great job with that grant and that grant got funded. And I was crazy enough to write a new pregnancy cohort in ECHO. And so, you know, it was, I was chair at Hackensack. It was my pajama time project, right? I wrote that ECHO grant till midnight every night, Saturdays, Sundays. It was down to the wire. I wasn't even sure I would get it in before that five o'clock deadline.

Judy Aschner (45:03)

Off it went. It was a Hail Mary. I was like, yo, there's no way they're going to give me $32.7 million, which was my seven-year budget for this grant. But it went in and yeah, it got funded. So I now have this wonderful pregnancy cohort where we're recruiting pregnant women into ECHO.

All less than 20 weeks of gestation. They can't be more than 19 weeks and six, seventh days. We're recruiting from my institution in New Jersey at Hackensack University Medical Center, where I have a spectacular research team. Like they are so amazingly awesome. And from Prentice and Lurie, they are my other site. We've already blown our recruitment goals out of the water for ECHO. We're such a great job of recruitment. this one, this one, yeah, no, it's great. We have goals for transitioning from UG3, which was the first two years of ECHO, to UH3, which is the last five years of funding. And to meet those goals, there are all sorts of metrics, but one of them is certain number of

Betsy Crouch (46:04)

And we could do a podcast on that. How to blow recruitment goals out of the water.

Judy Aschner (46:25)

Study subjects we said we'll recruit by February 28th. We've already exceeded it. And our demographics for underrepresented groups also, you know, 200 % of our targets. So that's really going well. But that's due to my research team. They're just amazing. And this grant that I wrote was because I got really interested in the fact that ECHO really wasn't being very inclusive of children with disabilities. That we had a huge amount of research and papers coming out on children with developmental, neurodevelopmental disabilities, but absolutely nothing on children with motor or sensory disabilities. And throughout the seven years of the first cycle of ECHO, I started getting more and more interested in this area and realizing how much environmental science needs to be done to better understand outcomes for children with disabilities. And I started being very vocal in ECHO about the fact that we had failed to be inclusive of this population. But ECHO in cycle one also didn't ask the right questions to really do a good job of studying this population. So my new ECHO grant really focuses on high-risk moms.

Judy Aschner (47:52)

Most of the ECHO pregnancy cohorts are, they focus on healthy pregnancies and actually exclude women with genetic conditions and so on and on. We are recruiting everybody out of our high-risk MFM clinic. Lots of multiples. Sorry, that was a call from Israel, which I'll have to do later. So we really focus on high-risk moms trying to quote unquote enrich ECHO with children with disabilities. We have tons of multiple gestation moms. My cohort was the very first cohort to recruit a pregnant woman in the second cycle. And we were the very first cohort to have a baby born in ECHO in the second cycle. And they were 28-week triplets. So I'm really interested in environmental factors that impact health and outcomes for children with disabilities, but particularly interested in positive health. What are the factors that allow children with disabilities to do better than expected? You know, I love to flip things on their head. People are always interested in risk factors. I really want to know what are the resilience factors? 

What are the things that allow these children to thrive?

Betsy Crouch (49:02)

I loved that part. Yeah.

Judy Aschner (49:20)

Because if you can understand what allows a child with a disability to thrive, you will learn a lot about thriving children in general. so that's my, those are my sort of a broad description of my specific aims in this next cycle of echo with my pregnancy.

Betsy Crouch (49:40)

Thank you so much. I think there's so much that we in the field have to be grateful to you for. I think the emphasis, especially on including underrepresented groups, such as children with disabilities, I mean, that's what it's really all about. And I could see there is this emphasis on positive outcomes on the ECHO website. And I wondered if that was just a little bit of Judy Aschner personally deciding that like, this is not going to be a doom and gloom story. This is also going to be about how we can enable the best possible outcomes from a variety of children, you know, so that we can support this beautiful, know, cohort of children and lives that we see, you know, at their first start in the NICU. So thank you so much.

Judy Aschner (50:29)

Yeah, I can't take too much credit for that. ECHO has a number of health outcomes that have been part of its focus from day one in the first cycle. And positive health was one of them. But thinking about children with disabilities and positive health, I I had to choose what my exposure was and what my outcome was. And I chose positive health as my outcome, one of the few cohorts in cycle two that did. And I think for children with disabilities, this is a particularly important area to focus on.

Judy Aschner (50:59)

So, and that goes describes, defines the environment very broadly. It isn't just the air we breathe and the water we drink and the chemicals in our environment, but it's the built environment, the social environment, your community, your home, your schools, whether you have access to care, there are so many factors that really influence long-term child health. And I have to say that one of the things Echo has truly done for me was redefine in my head what long-term outcomes mean.

I think we, neonatologists, think if we follow a kid to one or two years, we're doing great long-term follow-up. And thank you to the FDA for saying that 36 weeks cannot be our endpoint and that we need to look at what's happening nutritionally, growth-wise, lung development-wise, so on and so forth, neurodevelopment out to a year or two. Well, for ECHO, it's 22 years.

Judy Aschner (52:09)

And we have, you the LGAN study in ECHO that, you know, some of those LGAN children have already aged out. They're already beyond age 22. And as I said, my cohort, I have children who are adolescents already. And so I'm very excited that we can take these children that we've been following and will follow for at least 14 years and for a segment of that original ECHO DINE Grant, they were the PROP babies that we recruited in 2011, right? And some of those PENUT Babies and Anne Marie's NICU Health Cohort. We've been following these kids for a long time. And I think it's really important to connect the dots to what we do in the NICU and what are the early life exposures that ultimately determine whether these children thrive and have a meaningful life. And I've also learned that, you know, meaningful is different for different families and we need to be respectful.

Betsy Crouch (53:14)

I didn't know it was possible to conduct a longitudinal study of that magnitude in the US. And here is Judy Aschner showing us that it's possible. Yeah, so I mean, there have been many high points, but I think that is probably the highest high point. And in the interest of time, we'll transition to something fun.

David (53:15)

Amazing.

Betsy Crouch (53:36)

As we were prepping for this interview, Dr. Aschner told us that she's got something really exciting. And so I have been, yeah, I have been on the edge of my seat. I mean, also deeply absorbed in our conversation. So what do you like to do for fun, Dr. Aschner? What do you and your lab like to do?

Judy Aschner (53:36)

Okay.

I don't know about that, but...

So there are two big aspects of my life outside of now my full-time physician scientist role. And one of course is I told you I have four children. My seventh grandchild was just born a few weeks ago and number eight is in the cooker due in April. So that is a big focus. But outside of my family, my mental health, my physical health, my social life all revolves around rock climbing. I am an avid rock climber! I climb three days a week. I'm in the climbing gym at least eight, sometimes nine hours a week. I'm able to do that much better now than I could when I was chair and trying to do my research in my pajama time.

Judy Aschner (54:54)

I have traveled all over the world to climb. I have just come back from a climbing trip in the Dolomites in Italy, the Italian Alps. Last year I climbed on the island of Kalymnos in Greece, the Aegean. I've climbed in Red Rocks Canyon and Joshua Tree and Rumney, New Hampshire and North Carolina and mostly up at the Gunks here in New York State.

Judy Aschner (55:24)

I only climb in nice weather though, outdoors, but indoors, I climb three times a week. It's, it is really my mental health. And I didn't start climbing until I was in my mid-sixties, just before the pandemic. And I was terrible at it initially. And then the gym shut down when COVID hit.

And, you know, like we all came out of the fog, because COVID was, you know, indescribably horrible. Here in New York, New Jersey, we were at the epicenter. I've never worked so hard. Seven days a week, it was crazy what we did in that children's hospital during COVID. But when the gym reopened late fall of 2020, I said, okay, I've been doing nothing except this craziness and I really need to do something for me. And I decided I was going to start climbing three days a week and that's when I really started making progress. And then it just, I love this sport. I love this sport and yeah, even with my sore hip, I still climb three days a week.

Betsy Crouch (56:42)

You win. That is phenomenal. From New England Journal to the front cover of Outside Magazine, Dr. Judy Aschner.

Judy Aschner (56:43)

No, not really, but it is a fabulous sport. I climb with my children sometimes. I climb with my grandchildren. Yeah, it's really fun.

David (57:00)

Can I ask you a question? Just because you talked about that so passionately and I've climbed a little, but I mean, I think there are a lot of us get our mental sort of break by doing something that takes exertion and a lot of focus. And I wondered when you're climbing, do you think about your science or is it a time to be completely disengaged from that because you're so focused on your next handhold where your foot's going to go and things like that?

Judy Aschner (57:28)

Exactly the latter. Like, I can't think about anything but how I'm going to make that next move. And I don't boulder. I'm too old, I'll break. I only top rope, right? Sometimes multi-pitch climbs outdoors, but I top rope, I now lead climb. And yeah, I am focused on nothing but how to make that next move.

And in the gym in particular, on top rope, I'll try anything. you know, climbs that are way beyond my pay grade. I'm not worried about it. Outdoors I'm very cautious and I climb very carefully and cautiously and downgrade. My climbs when I lead I'm also very cautious. But on top rope in the gym, yeah, you can put me on an 11D or a 12 and I'll give it a go.

I don't always succeed, but I'll keep working at it until I do. I'm very stubborn. And you know, it keeps me mentally sane. Physically, it's an incredible total body workout, right? And I have a ton of climbing friends who, you we go out to dinner after climbing sometimes and celebrate each other's birthdays. And it's just, it's become really a big focus of my life.

David (58:26)

Determination again, it's a great story.

That's fantastic. Thank you so much.

Betsy Crouch (58:57)

I'm quite inspired. Maybe I'll take up climbing.

Judy Aschner (59:00)

So fun. So fun. It's really good.

Betsy Crouch (59:03)

Yeah, I have my sister-in-law's sister who's also scientist and she and her now husband.

And they do these insane things where they will like sleep, anchored to a cliff, and that's about it. And they honeymooned that way and...

Judy Aschner (59:25)

I climbed six days straight in the Dolomites this summer. my goodness. It was incredible. It was so beautiful. It was amazing. And I love to cook. So if I go on a climbing trip with a whole group, I usually make the meals.

Betsy Crouch (59:44)

Okay, well David and I now have a new life aspiration, which is to get invited to Judy Aschner's climbing trips.

Judy Aschner (59:49)

Ready?

City come visit me! I have room!

David (59:54)

yeah, there's great climbing there. Nearby.

Judy Aschner (59:58)

There's great climbing on the west coast.

Betsy Crouch (1:00:01)

Well, scaling new heights with the At the Bench podcast and Judy Aschner. So David, you want to wrap this up?

David (1:00:04)

Perfect. Nice.

Yeah, thank you so much, Dr. Aschner. That was so fantastic to talk with you. I learned so much and definitely motivated again by hearing your stories about your career path. Thanks so much, Betsy, for hosting today's program. I'm David McCulley. Thank you so much to our audience. We'll meet you back here at the bench. Have a great day.

Judy Aschner (1:00:33)

Thanks. Bye, everyone.