#345 - 🔬Genetics and Neonatal Lung Disease: A Conversation with Dr. Jennifer Wambach

Hello Friends 👋

In this episode of At-the-Bench, hosts David McCulley and Misty Good interview Dr. Jennifer Wambach, a neonatologist and researcher specializing in rare neonatal lung diseases. Dr. Wambach shares her journey into neonatology, her research on genetic lung diseases, and the importance of mentorship in developing future physician-scientists. The conversation also covers the Undiagnosed Diseases Network, current research on genetic lung diseases including ABCA3 deficiency, and the challenges faced in rare disease research. Dr. Wambach emphasizes the need for resilience and adaptability in scientific careers, offering valuable advice for early-career investigators.

Link to episode on youtube: https://youtu.be/XSmNnx8HA78

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Short Bio: Jennifer Wambach, MD, MS, is an Associate Professor of Pediatrics at Washington University School of Medicine (WUSM). Dr. Wambach is the co-program director of the neonatal perinatal medicine fellowship program at WUSM/St. Louis Children’s Hospital. Her research goals are to understand the disease mechanisms of rare neonatal and pediatric developmental lung disorders, to identify pharmacologic strategies for treatment of these disorders that are often fatal without lung transplant, and to use genomic and transcriptomic technologies to identify the genetic etiology of birth defects and rare phenotypes among infants and children

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Featured manuscripts from Dr. Jennifer Wambach

Nevel RJ, Brennan SK, Wambach JA. Genetic Disorders of Surfactant Metabolism. Neoreviews. 2025 May 1;26(5):e328-e338. doi: 10.1542/neo.26-5-014. PMID: 40306683.

Voss LA, Nevel RJ, Wambach JA, Nogee LM, Deterding RR, Casey AM, O'Connor MG, Craven DI, Taylor JB, Deutsch GH, Tam-Williams JB, Steffes LC, Brennan SK, Santiago MT, Sadreameli SC, Heras AF, Powers MR, Popova AP, Bansal M, Hamvas A, Gower WA, Urrego F, Young LR; ChILD Registry Collaborative. Genetic Testing Utilization in the U.S. Registry for Childhood Interstitial and Diffuse Lung Diseases. Pediatr Pulmonol. 2025 Apr;60(4):e71073. doi: 10.1002/ppul.71073. PMID: 40167520; PMCID: PMC11960725.

Wambach JA, Nogee LM, Spielberg DR, Cole FS, Roberts DM, Murphy S, Garcia CK. Interstitial Lung Disease and Lung Cancer Associated with a Monoallelic Novel Variant in SFTPB. Am J Respir Crit Care Med. 2025 Jun;211(6):1085-1088. doi: 10.1164/rccm.202412-2411RL. PMID: 39970392; PMCID: PMC12175957.

Sun YL, Hennessey EE, Heins H, Yang P, Villacorta-Martin C, Kwan J, Gopalan K, James M, Emili A, Cole FS, Wambach JA, Kotton DN. Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations. J Clin Invest. 2024 Jan 16;134(2):e164274. doi: 10.1172/JCI164274. PMID: 38226623; PMCID: PMC10786693.

Wambach JA, Wegner DJ, Kitzmiller J, White FV, Heins HB, Yang P, Paul AJ, Granadillo JL, Eghtesady P, Kuklinski C, Turner T, Fairman K, Stone K, Wilson T, Breman A, Smith J, Schroeder MC, Neidich JA, Whitsett JA, Cole FS. Homozygous, Intragenic Tandem Duplication of SFTPB Causes Neonatal Respiratory Failure. Am J Respir Cell Mol Biol. 2024 Jan;70(1):78-80. doi: 10.1165/rcmb.2023-0156LE. PMID: 38156804; PMCID: PMC10768837.

Xu KK, Wegner DJ, Geurts LC, Heins HB, Yang P, Hamvas A, Eghtesady P, Sweet SC, Sessions Cole F, Wambach JA. Biologic characterization of ABCA3 variants in lung tissue from infants and children with ABCA3 deficiency. Pediatr Pulmonol. 2022 May;57(5):1325-1330. doi: 10.1002/ppul.25862. Epub 2022 Mar 17. PMID: 35170262; PMCID: PMC9148430.

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

David McCulley: Hello and welcome back to At-the-Bench, the Incubator podcast focusing on neonatology physician scientists. My name is David McCulley. I'm a neonatologist and basic developmental biologist here at the University of California in San Diego. And I am very honored to co-host this program with Misty Good. Misty, do you want to introduce yourself and our guest for today?

Misty: Sure. Hi David, and hi Dr. Jennifer Wambach. I'm Misty Good, a neonatologist, scientist, and division chief of neonatology at UNC Chapel Hill. I’m honored to be co-hosting today and interviewing our very special guest, who I’ve had the honor of working with for several years previously—Dr. Jennifer Wambach. Jen, would you like to introduce yourself?

Jennifer Wambach: Hi, I'm Jen Wambach. Thank you for the invitation to chat today, Misty and David. I appreciate it. I’m an associate professor of pediatrics and neonatologist at Washington University in St. Louis, and I do my clinical time at St. Louis Children’s Hospital. I’m also the co-program director for our fellowship program. Thanks again for the invitation.

David McCulley: Awesome. It's really an honor to have you here. You are a perfect example of a successful neonatologist physician scientist, and it’s great to be able to talk with you about how you got your career started and what’s been most interesting for you to study.

I know you as a neonatologist who studies genetic mechanisms of newborn lung disease. Could you give a general overview of your research program—what you’re focusing on now—and then we’ll get into what motivated you to pursue that line of research?

Jennifer Wambach: Sure. My lab really has two main goals. The first, as you described, is focusing on rare neonatal lung diseases. St. Louis Children’s Hospital is one of the few hospitals in the country that can offer infant lung transplant. We take care of a number of these babies clinically, but I became very interested in these diseases because they usually have a genetic origin, and I had a strong interest in genetics coming into neonatology fellowship. I also found them particularly interesting because they are usually not diagnosed before birth, unless there is a family history. These are typically term babies who, for every intent and purpose, should be healthy, but have severe breathing problems at birth. Unfortunately, we don’t have a lot of treatments right now. For those who have progressive respiratory failure, lung transplant is the only definitive treatment. I’m very interested in modeling these diseases after the success with cystic fibrosis. The specific gene I study, ABCA3, is very similar to CFTR, and we’re trying to take lessons learned from cystic fibrosis and apply them to rare lung diseases, including ABCA3 deficiency.

The second focus of our lab is using exome, genome, and transcriptome technologies to find the etiology of rare diseases in infants and children. I was fortunate to transition to faculty as many of these technologies were becoming available and much less expensive. It has been an interesting journey I’ve taken with a number of families—each baby or child has their own story as we navigate that process. We’re fortunate to be part of the Undiagnosed Diseases Network (UDN), funded by the NIH. WashU is one of 12 clinical sites, and we also have a Model Organism Screening Center (MOSC). We receive funding not only from the NIH, but also from our Department of Pediatrics and School of Medicine to continue that work. It’s not necessarily the path I would have predicted as a fellow, but it’s been a lot of fun.

Misty: I was going to ask you about that—if you could tell our listeners about your journey and when you really started to get excited about science. Was it a particular patient, mentor, or point in your career path when you got bit by the scientific bug?

Jennifer Wambach: I did some bench research in college and enjoyed it. At that point, I was deciding between graduate school, pursuing a PhD, versus going into medicine. I spent a summer studying a flowering weed species in Virginia—we collected leaves and did genotyping. That was my first real hands-on exposure to genetics, and I really enjoyed it, but I missed the people side of science. That’s when I decided I was drawn to the clinical and medical aspects, so I pursued an MD.

To be honest, I wasn’t that aware of MD-PhD programs at the time, and seven years seemed like a lifetime when I was 22. So I went to medical school, then residency. When I looked for fellowship positions, I still wanted research opportunities, and I found that at WashU in St. Louis. I’ve been here ever since. During fellowship, I found wonderful mentors who combined genetics with neonatology, and that’s when I really saw the two fields coming together.

David McCulley: That’s really exciting. It’s helpful to hear what motivated you and how you established your path. You mentioned in your overview how genetics was motivating and interesting to you, even as an undergrad. Can you explain how going from plant genetics was stimulating, and how you then thought about pursuing genetics research during fellowship?

Jennifer Wambach: Neonatology was particularly interesting to me because there’s so much genetics involved in the care of critically ill infants. Those two interests came together naturally. I briefly considered clinical genetics, but I really liked the fast-paced environment of NICU care.

My first lab project was looking at DNA variants in the surfactant protein C gene in a cohort of infants. At that time, we were sequencing one gene at a time. During my fellowship, it grew, from one gene, to five genes, then a 1,500-gene panel, then exome and genome sequencing. I was very lucky to be training when that dramatic change in genetic testing became available.

There were so many NICU applications. I remember being able to access exome sequencing on a research basis and thinking about how many families we could help find diagnoses for—infants who were sick without answers, many of whom had passed away. Doing trio-exome sequencing identified causes of some birth defects and extreme phenotypes. That was very rewarding. For me, it was two interests converging at the right time.

David McCulley: I remember that must have been near the end of your training. As a fellow at UCSF, I recall we were sending samples to WashU because it was the place doing cutting-edge research on the genetic basis of complex lung disease. All the experts were there. At the time, we had so few options to offer families. Over the past 15 years, the technology has changed so quickly and enabled so many more diagnoses for families with babies with complex diseases, especially newborn lung diseases like you study. It seems that in addition to identifying diagnoses, you’re now building toward using the genetic diagnosis to develop new therapies. I’m sure we’ll get into that, but that must have been a motivating idea as well.

Jennifer Wambach: Yes, for sure. We now consult virtually with families and neonatologists across the country when they encounter these rare genetic lung diseases. Each neonatologist may only see them a handful of times in their career, but we can offer potential therapies and walk families through the process. That’s an important part of my job, and I get to interact with colleagues nationwide.

Right now, therapies are limited, but we have hope for gene therapy for some of these disorders. Mouse models have shown promise—for example, correcting surfactant protein B deficiency with gene therapy. We’re very interested in identifying medications and potential gene therapy for ABCA3 deficiency as well. Understanding the genetics and biology is critical for developing these therapies. It’s exciting to think that by the end of my career, we may have treatments for these previously fatal disorders.

Misty: That's fantastic. As someone who used to work with you, and now that I’m at UNC while you’re at WashU, I can say it’s such a wonderful resource when we have a rare genetic lung disease—or even a suspected one—that we can pick up the phone and chat with you.

I was curious because we have a lot of fellow listeners who look at many of the people we host and think, “That can never be me” or “I could never be an expert in this field.” But you’ve shown that by pursuing your interest in rare genetic lung diseases, you’ve become the go-to consultant not just in the U.S. but internationally. Could you tell our listeners how that journey happened? I know you were funded with a K and you’ve been incredibly successful with grants. Could you talk a little about your early collaborations, mentorship along the way, and how you went from graduating fellowship to becoming the expert you are now?

Jennifer Wambach: That’s very kind of you. I think I’m always learning, and there’s certainly much more to learn. One of the exciting things about clinical exome and genome sequencing is that we’re continually identifying even more rare diseases—not just in neonates with lung disease, but in other phenotypes as well.

To be honest, when I first started in the lab, I was interested in the gut—the intestine. But my mentors were interested in the lung, and I said, “I like genetics, I could learn to love the lung.” And I did. I learned to love it along the way.

For me, mentorship was probably as important, if not more important, than the actual organ system focus—especially as a fellow. I had wonderful mentors. F. Sessions Cole and Aaron Hamvas were here at WashU, as David mentioned. They are experts in surfactant biology. In fact, the very first infant with surfactant protein B deficiency was identified in the St. Louis Children’s NICU. It’s a great story—Aaron Hamvas and Sessions Cole were attendings, Larry Nogee was a junior faculty, and Robin Deterding, now a leader in pediatric pulmonology, was a medical student. It’s amazing how one patient can influence so many careers.

Sessions and Aaron were my primary mentors during fellowship. Larry Nogee, now at Johns Hopkins, identified many of these disorders and also mentored me. I got to know him through conferences—he would stop by my posters, we’d have breakfast meetings, and that led to more opportunities. I also connected with pediatric pulmonologists like Robin Deterding at Colorado Children’s and Lisa Young at CHOP have also been mentors to me. Even though we were never at the same institution, they gave me opportunities and we’ve collaborated scientifically. A lot of it came with time and focusing on a couple of projects, and getting them far enough for a presentation, whether a poster or platform. People would come up afterward, ask questions, and I’d follow up on those contacts.

I know people say you should learn to say no, but I think saying yes is also valuable. Take advantage of opportunities to interact with faculty, whether at a conference, webinar, or interest group. That’s a great way to build connections.

Misty: Yeah, that’s a great point. You’ve been so successful at that, and as a fellowship director, you’re mentoring the next generation to do the same. Helping trainees become neonatal physician scientists is incredibly important. Do you want to talk about that a bit?

Jennifer Wambach: We have a large fellowship program, and my co-director Sam Julian and I help fellows find their research mentors. It’s exciting to be part of their career development and guide them toward research that sparks their interest. Some come in very open-minded about their project, and we try to help them identify mentors who will be invested in them and help shape an independent project. Others come in with a more defined idea. In both cases, helping them identify strong mentorship has been very rewarding.

We’ve had several fellows go on to become physician scientists, and it’s been fun to watch their careers develop and to be even a small part of that process.

David McCulley: Yeah, you have a fantastic program. It’s been very successful, definitely a leader in supporting physician scientists early in their careers. Since you’re the fellowship program director, I wanted to ask about mentorship specifically.

When I was interviewing for fellowship at UCSF, I met with Ron Clyman, who gave me advice I still share. He said you should try to find a mentor who teaches you to ask really interesting scientific questions. That might be more impactful than even having someone in your exact research topic. His idea was not to limit yourself to a lab already doing exactly what you want, but to find a mentor with a knack for identifying interesting, motivating questions. I thought that was great advice, and I’ve tried to pass it on to fellowship applicants and med students.

Jennifer Wambach: Yes, I think that’s great advice. Each fellow is a little different in the support they need. Some thrive with open-ended questions and can explore those independently, while others need more structure. For the latter, it’s helpful to connect them with mentors who have a track record of training physician scientists or clinical fellows. That structure helps them build a foundation, whether continuing along that project or taking a tangent.

Each fellow comes in with different backgrounds and interests, so we really try to individualize projects. That’s been a big focus for us.

Misty: Jen and I used to work together on fellowship, and she was always the one who could find the perfect mentors across WashU. We would meet with them, align expectations, and it was such a great experience working with you on that.

David McCulley: Can you talk more about that? WashU has such a wide range of research topics, and I think it’s important that you were looking for mentors not only outside neonatology, but sometimes outside pediatrics—or even the medical school. That’s something we’ve tried at UCSD, too. But there’s always the challenge: how do you structure training for a neonatology fellow with service responsibilities and call time in such a rich research environment?

Jennifer Wambach: Misty and I spent a lot of time buying people coffee and talking about their work. Each fellow has different interests, and sometimes those aren’t represented in our division or even our department. In those cases, we’ve gone outside. WashU is a very collaborative environment, and I’ve sent many emails to faculty asking if they’d meet or do a quick Zoom to learn about our fellowship and how much time fellows have for research. Usually Sam or I make those initial introductions to gauge fit with the mentor. We also join the fellow’s first meeting with the potential mentor. That way, we can answer logistic questions—like service months, call schedules, or post-call rules—that faculty outside our division might not know. That has worked well.

Another tip I’ve learned: it’s very helpful for fellows to have someone in the lab (a manager, postdoc, or staff scientist) who they can meet with daily. Faculty mentors are often busy with grants, service, or meetings, but having that day-to-day contact is critical for building skills and success early on.

Misty: Since you touched on it, could you talk more about the Undiagnosed Diseases Network (UDN)? Specifically, how cases go from the patient to the bench and back to the bedside? It’s such a unique opportunity to see science translate to patient care.

Jennifer Wambach: We became part of the UDN in 2018 and were very excited to be selected for phase three. Patricia Dickson, chief of clinical genetics here at WashU, is the PI, and I am a co-investigator for our site. There are 12 clinical sites across the country with a centralized application system. Families, pediatric or adult, apply through the portal. Based on geographic location, they’re referred to a site, and then we review their application and medical records. We try to identify individuals most likely to benefit from whole genome sequencing, particularly those with suspected genetic conditions. To be honest, many families coming to us now have already had clinical whole genome sequencing. We review some very complex cases. Now we have the technologies to try to identify those monogenic causes of extreme phenotypes including birth defects. Those are the individuals whom we are most successful in solving through the UDN.

If selected, patients come on site for a clinical evaluation. About half of our referrals are internal and half external. We review their records and whole genome results, typically performed clinically at Baylor. Usually we don’t find the answer with that initial analysis, so we proceed with research re-analysis. We have a wonderful bioinformatics team led by Dan Wagner and Alex Paul, who reanalyze whole genome data to identify potential etiologies. From there, it becomes individualized. Sometimes there’s a candidate gene already studied in a model organism with a relevant phenotype. Other times, little is known about the gene. In those cases, we use resources like GeneMatcher, a database where investigators can share de-identified information about genes or phenotypes to connect with others studying the same thing. We’ve solved many cases that way. We also have the Model Organism Screening Center (MOSC) within the UDN. Candidate genes or variants can be studied in fruit flies, worms, or zebrafish.

It’s often a combination of these resources. In our lab, we also do in vitro studies, like cell culture, RNA sequencing, and sometimes long-read DNA or RNA sequencing. These are research tools not available clinically or covered by insurance, but they’ve been essential for solving some UDN cases.

David McCulley: Can I ask you some more questions about that? I think that might be something our audience doesn’t know as much about. You said you use a screening process. Does each site screen cases, or do you get sent cases based on your site’s expertise? How does that process work?

Jennifer Wambach: We receive applicants based on geography. We cover a six- or seven-state catchment area in Missouri and the surrounding states, so we review the applications in our region. There isn’t specialization within the UDN sites.

That said, for some of the unsolved cases we have meetings with all of the sites to discuss them. Certain experts may be there. We also use the resources available here at WashU, drawing on all of our specialists during a clinical visit. For example, a patient may see an adult rheumatologist or infectious disease expert; it really depends on their symptoms.

David McCulley: And then the same for the model organism core facility – do all the sites have something similar, or do they have their own cores based on expertise?

Jennifer Wambach: There are Model Organism Screening Cores at WashU, Baylor, and Oregon. So there are only three in the U.S. They receive referrals from all of the UDN clinical sites. Based on homology and what’s known about the ortholog in the worm, fish, or fruit fly, as a group we decide which organism would be best to model.

Misty: Do the Model Organism Screening Centers (MOSC) have different areas of expertise, or how are they organized?

Jennifer Wambach: It’s really based on the organism. The choice depends on which one is best suited to study the candidate gene. We also reach out to investigators on campus if there’s a gene identified as a potential explanation for a participant’s phenotype. Sometimes those investigators already study that gene and may even have the tools to model the variant, or it may be completely new to them. Each participant has their own story, but the MOSC is an incredibly valuable resource.

David McCulley: It’s so exciting because it demonstrates the power of genomics. The other exciting thing is having a multi-institutional collaboration that makes it possible to diagnose rare and complex conditions. There are also potential treatments emerging from these investigations. It clearly takes a very multidisciplinary research program to do this work, since each case is so rare and complicated. The phenotype is often difficult to fully understand, and demonstrating the genetic basis of disease can be challenging. Doing this work across institutions is inspiring for all of us who want to provide answers for families and hopefully treatments in the future.

Jennifer Wambach: Yes, for sure. It’s been a wonderful group to be part of, and we hope it continues in the future.

Misty: Fantastic. I wanted to shift a little to talk about your recent work and current active studies happening in your lab and research program. I saw you had written a paper on interstitial lung disease and lung cancer associated with surfactant protein B. As neonatologists, we don’t see lung cancer per se. Can you talk about that paper and how your current work all comes together?

Jennifer Wambach: That paper described a rare form of a rare disease. Two infants came to us for lung transplant evaluation. They had typical genetic testing—panel or exome sequencing—but only had a single variant in the surfactant protein B gene. For one infant it was inherited, for the other it arose de novo. Clinical labs weren’t calling this pathogenic because surfactant protein B deficiency is an autosomal recessive condition, and here there was only a single variant. But both infants had the exact same variant, which raised suspicion this might represent a different mechanism.

Over time, Larry Nogee and I, along with David Spielberg in Houston, identified more individuals with the same variant—especially in the family with the inherited form. Among them were adults with pulmonary fibrosis and some with lung cancer. Some had been sequenced, others had not, but the variant seemed to track with multiple lung phenotypes.

That pattern is similar to what we see with pathogenic variants in surfactant protein C. This was just the first time we had observed it with surfactant protein B. Then Larry happened to meet Christine Garcia, who studies adult pulmonary fibrosis. She had pedigrees showing the same surfactant protein B variant in families with adult interstitial lung disease and lung cancer. Putting all of that together, we identified multiple individuals with the same dominant variant presenting with a spectrum of disease: neonatal respiratory failure, childhood interstitial lung disease, adult pulmonary fibrosis, and adult lung cancer. We published those pedigrees so clinical labs could recognize this variant. In fact, in one case, a baby was scheduled for a lung biopsy because this was the only variant identified. After discussion with the clinicians and pathologist, we realized this was the diagnosis—so we like to think we saved that baby from a lung biopsy.

It’s a rare form of a rare disease, but it shows the importance of studying rare conditions, which can also provide insights into more common diseases like pulmonary fibrosis or lung cancer.

Now we need to understand the biology behind it – that’s the next project. We try to collect specimens from infants and children with these rare conditions. We’re so grateful to the families who participate in research studies, helping others with the same condition.

We also collaborate with Daryl Cotton at Boston University, who takes skin fibroblasts from affected infants and children, develops iPSCs (induced pluripotent stem cells), and then induces alveolar type II cells to model these disorders. The goal, again, is to identify therapies.

David McCulley: That’s very exciting, to get to the next level of individualized patient treatment based on genotype, using cell-based biology.

You also highlighted an important point: even when one gene is implicated, the actual variant can dramatically affect protein function and the phenotype. Your work with surfactant protein B and cancer really shows this. It’s complicated. Families often think, “Okay, I have this disease, I know the gene is associated with it.” But the phenotype can vary widely depending on the specific mutation. Could you share some general thoughts about that complexity—how we move from genotype to phenotype to therapy?

Jennifer Wambach: That’s a great question. For ABCA3, the gene we study most in our lab, there’s a fairly clear genotype-phenotype correlation. If you have biallelic loss-of-function variants—frameshift or nonsense—infants present with neonatal respiratory failure and sadly pass away within the first few months without lung transplantation. But if you have a missense variant in trans with either a loss-of-function or another missense variant, it’s much harder to predict prognosis. That’s when we need cell-based models to understand how different variants cause disease. We’ve done this with some ABCA3 variants. We use cell systems to express missense variants and study how they disrupt surfactant metabolism. Some interrupt trafficking of ABCA3 to the lamellar bodies. Others traffic normally but fail to pump phospholipid.

Understanding these mechanisms is crucial because that’s how we can identify therapies. Cystic fibrosis is the model—many CF therapies are based on the mechanism of specific CFTR variants. For babies with biallelic loss-of-function variants, gene therapy or CRISPR editing may be the only option. But for those with missense variants, medications might help restore trafficking or improve transport.

It’s complicated, but that complexity makes science exciting. When you can identify those correlations and associations, it’s very gratifying. Much of the work is piecing together all the information to make sense of the disease.

Misty: It’s so challenging studying the rarest of rare diseases. Can you talk a little about that, or any challenges you’ve faced as you’ve been building and sustaining your research career?

Jennifer Wambach: Yes, these are certainly rare disorders, but many of them have applications to more common diseases. For example, ABCA3 deficiency is an autosomal recessive condition; you need both copies of the gene affected to have the disease. But we’ve found that if you have just a single variant in ABCA3, those babies are much more likely to have respiratory distress syndrome, even at term or late preterm. Many of them improve with CPAP, maybe intubation and surfactant, and ultimately do quite well. It’s been fascinating to find that, yes, these diseases are rare, but they can shed light on common conditions.

Resilience is also important. Some discoveries come quickly and are very exciting, like the surfactant protein B story I shared with its range of phenotypes. Others take much longer to figure out. I received good advice as a fellow: a researcher should think like a farmer. A farmer has multiple crops going at once—some harvested in spring, some in fall. Similarly, it’s good to have several projects going. Some wrap up quickly, others take much longer. That balance helps sustain momentum.

Misty: I love that. I’m going to bring that to the lab this week: be like a farmer. That’s why we have so many ongoing projects. Sometimes people in the lab want only one project, but I think it’s good to have both high-risk and low-risk projects. Especially for fellows, who are on a condensed timeline and need a publication by the end of fellowship, a shorter-term, lower-risk project is essential. The high-risk project may continue longer, like a farmer’s crops.

David McCulley: That’s great advice. I remember being told to focus and to make sure one project worked. But often, what seems like a small hurdle becomes a major barrier. There probably isn’t one best way to give advice on this, but I like the idea of project diversity. I also like the farmer analogy—the foresight to anticipate the unanticipated. What happens if there’s a flood or terrible weather? How do you plan for what you can’t foresee, so you can still be productive at the end?

Jennifer Wambach: I’m not sure I have the answer to that. There have certainly been challenges in my 15 years as faculty—COVID, funding, and all the usual hurdles. But I’ve been lucky to have the support of my division, department, and medical school to keep the work going.

David McCulley: You’ve also built very successful collaborations outside your institution. I’m sure those have helped you maintain momentum and a diverse research repertoire. Those inter-institutional collaborations inspire me. They’re often the source of the most interesting questions because people approach ideas from different perspectives, and you learn from each other.

Jennifer Wambach: Yes, that’s one of the most fun parts of being a physician-scientist—collaborating outside your institution. Whether you see those colleagues once or twice a year, it’s always exciting to connect over science. It’s special to have those relationships. I didn’t anticipate that as a fellow, but it’s become one of the most rewarding aspects of my career.

Misty: Speaking of fellows, as we come to the end, could you share the best piece of advice you’ve received or advice you’d give to fellows or early-career investigators pursuing a physician-scientist career?

Jennifer Wambach: You don’t have to have it all figured out today. Keep an open mind and give science a try. There will be setbacks – that’s part of the process. Just keep asking questions. It’s okay not to know all the answers. One of the fun things about science is that the field evolves quickly. I’m constantly learning new things. In some ways that’s challenging because I never feel like the expert on anything, but it’s also what makes it stimulating, rewarding, and exciting.

Keep an open mind. If you have to pivot to a different project, it’s okay. Work hard, but also make sure you enjoy what you’re doing. Ultimately, it’s your career – you need to be happy day to day.

Misty: That’s wonderful advice. Hearing you talk about it warms my heart and makes me miss working with you.

David McCulley: Can I ask one more? We like to end with something that shows our humanity as people who do this work. What’s something you like to do for fun with your research group or your family? Any hobbies that help you clear your head?

Jennifer Wambach: We’re a big soccer family. I have three boys. I just dropped off my oldest at college—he’s at WashU, which makes the transition easier because I’ve already seen him four times in the last eight days. He plays soccer, and I have a 13- and an 11-year-old who also play.

We’re season ticket holders for STL City, and I’m excited our city finally has its own team. I often bring my laptop to soccer practice and games. Some parents wonder why I’m working, but I love the flexibility. I can get some lighter work done and sometimes even have good ideas while I’m there. So yes, I’m the mom with the laptop at soccer practice, but I’ve really appreciated being able to integrate both parts of my life.

David McCulley: You never know when inspiration will strike, so you have to be ready. I bring a notepad to events just for that reason. Something will click, and I want to capture it. That’s wonderful. Here in San Diego, we now have San Diego FC, a new team this year. My family and I went to see them play the Portland Timbers over the weekend. Soccer’s been a big part of my life, too. That’s awesome to hear. Thank you for sharing.

Misty: Talk about work-life integration – you’re living it every day. Thank you so much, Jen, for being on our podcast. We appreciate hearing about your career journey and how you’ve become a leader in the field. We’re so grateful for your words of inspiration.

Jennifer Wambach: Thank you. It’s always good to see you, Misty and David, and I appreciate the invitation.

David McCulley: Yes, thank you so much, Jen. And thanks to our audience—we’re so lucky to host this program. Hopefully this was another inspiring show for you. We’ll be back soon with another interview from At the Bench. Thanks for tuning in, and we’ll talk again soon. Have a great day.