#026 - Exploring Neonatal Platelet Biology (ft Dr. Christopher Thom)

Hello friends 👋

In this episode of At the Bench, Misty Good and David McCulley interview Dr. Christopher Thom, a neonatologist and leader blood lineage development. Dr. Thom discusses his training in hematology research and what inspired him to build an outstanding research program studying platelet biology and how his research is being translated to change transfusion care for patients. The conversation emphasizes the importance of collaboration in neonatology physician-scientist driven research.

Link to episode on youtube: https://youtu.be/7KEwCSYLLyA

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Featured Manuscripts From Dr. Christopher Thom

Coletti K, Hershey JA, Devine M, Taft J, Schinella J, Ajiboye S, Gibbs K, Lambert MP, Friedman D, Thom CS. An improvement project standardizing low prophylactic platelet transfusion dosing for infants. J Perinatol. 2025 Dec;45(12):1825-1832. doi: 10.1038/s41372-025-02347-5. Epub 2025 Jul 9. PMID: 40634587; PMCID: PMC12716995.

Wilken MB, Fonar G, Qiu R, Bennett L, Tober J, Nations C, Pavani G, Tsao V, Garifallou J, Petit C, Maguire JA, Gagne A, Okoli N, Gadue P, Chou ST, French DL, Speck NA, Thom CS. Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis. Stem Cell Reports. 2024 Sep 10;19(9):1264-1276. doi: 10.1016/j.stemcr.2024.08.001. Epub 2024 Aug 29. PMID: 39214082; PMCID: PMC11411305.

Gilmore LE, Chou ST, Ghavam S, Thom CS. Consensus transfusion guidelines for a large neonatal intensive care network. Transfusion. 2024 Aug;64(8):1562-1569. doi: 10.1111/trf.17914. Epub 2024 Jun 17. PMID: 38884350; PMCID: PMC11624464.

Thom CS, Davenport P, Fazelinia H, Soule-Albridge E, Liu ZJ, Zhang H, Feldman HA, Ding H, Roof J, Spruce LA, Ischiropoulos H, Sola-Visner M. Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets. J Thromb Haemost. 2024 May;22(5):1447-1462. doi: 10.1016/j.jtha.2023.12.022. Epub 2023 Dec 30. PMID: 38160730; PMCID: PMC11055671.

Wilken MB, Maguire JA, Dungan LV, Gagne A, Osorio-Quintero C, Waxman EA, Chou ST, Gadue P, French DL, Thom CS. Generation of a human Tropomyosin 1 knockout iPSC line. Stem Cell Res. 2023 Sep;71:103161. doi: 10.1016/j.scr.2023.103161. Epub 2023 Jun 28. PMID: 37422949; PMCID: PMC10507314.

Gu H, Devine M, Hedrick HL, Rintoul NE, Thom CS. High rate of extreme thrombocytosis indicates bone marrow hyperactivity and splenic dysfunction among congenital diaphragmatic hernia patients. Platelets. 2022 Jul 4;33(5):787-789. doi: 10.1080/09537104.2021.1994546. Epub 2021 Oct 26. PMID: 34697983; PMCID: PMC9038952.

Thom CS, Traxler EA, Khandros E, Nickas JM, Zhou OY, Lazarus JE, Silva AP, Prabhu D, Yao Y, Aribeana C, Fuchs SY, Mackay JP, Holzbaur EL, Weiss MJ. Trim58 degrades Dynein and regulates terminal erythropoiesis. Dev Cell. 2014 Sep 29;30(6):688-700. doi: 10.1016/j.devcel.2014.07.021. Epub 2014 Sep 18. PMID: 25241935; PMCID: PMC4203341.

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

[00:01] Misty Good: Hello and welcome back to At the Bench, the Neonatal Physician Scientist podcast of the Incubator. I'm Misty Good, a neonatologist, scientist, and Division Chief of Neonatology at UNC Chapel Hill. I'm co-hosting today with Dr. David McCully. David, would you like to introduce yourself and our guest?

[00:23] David McCully: Thanks, Misty. My name is David McCully. I'm a neonatology physician scientist at the University of California San Diego. I study the genetics of diaphragmatic hernia and lung and pulmonary vascular development. I'm honored to be co-hosting with you, Misty. And I'm really excited to talk today with our guest, Dr. Christopher Thom — an outstanding neonatology physician scientist at the Children's Hospital of Philadelphia (CHOP), and someone I've gotten to know over the last few years who is doing remarkable research in platelet biology and hematopoiesis. Chris, we'd love to hear a bit about what got you interested in the work you're doing and have you introduce yourself to our audience.

[01:14] Chris Thom: I'm flattered to be here and to be invited to the podcast. My name is Chris Thom. I'm at the University of Pennsylvania and the Children's Hospital of Philadelphia. I'm a neonatologist and physician scientist. My lab studies genetic determinants of hematopoiesis and bone marrow development, with a specific focus on platelet biology — which has come about organically as platelet transfusions and platelet biology have moved to the forefront of neonatal hematology.

My background as a physician scientist came through the MD-PhD program at the University of Pennsylvania, followed by residency and fellowship training at CHOP. I still remember, as a fellow, presenting to my division nearly 20 years of research on why platelet transfusions might be harmful to babies — culminating in the conceptualization of the PlaNeT-2 trial, which was published right at the end of my fellowship. That has driven much of the work and focus in my lab: trying to understand why we're seeing those detrimental effects and how we might correct them through both basic and translational approaches.

[02:39] David McCully: That's a great starting point, Chris. I wondered if you could say a little more about what motivated you early on — both to pursue the topics you're studying and to take the career path you've taken. I know you'd initially been drawn to hematology as a subspecialty.

[03:15] Chris Thom: For most of my adult life, I was going to be a pediatric hematologist. After college, I was a research technician with Charlie Roberts at the Dana-Farber Cancer Institute. He was a fantastic mentor who got me interested specifically in pediatric medicine, and I absorbed a great deal about the issues facing pediatric hematology-oncology. When I came to Philadelphia for Medical Scientist Training Program (MSTP) training, I fully expected to be a pediatrician and most likely a hematologist.

My PhD was in Mitch Weiss's lab — an outstanding pediatric hematologist who is now the chair of hematology at St. Jude. It was an amazing environment, with a mentor incredibly devoted to all of his trainees. I learned pediatric hematology from him. By the end of my PhD, I had training in cell and molecular biology specifically related to blood cell formation — red blood cell formation in particular — at the intersection of evolving genetics and Genome-Wide Association Study (GWAS) fields.

Then, as I completed medical school and started internship in pediatrics, I encountered all the other clinical fields in pediatrics. That's where I became drawn to acute care, intensive care, and procedural specialties — and fell in love with neonatology. In a way it was a last-minute decision, because I had chosen to pursue the Accelerated Research Program (ARP) here, which meant I had only two years of residency and had to apply for fellowship after essentially my intern year. It was during that intern year that I shifted tracks and decided to pursue a different clinical specialty.

[05:37] Misty Good: Can we pause there for a moment? I know some of our listeners may not be familiar with the accelerated research pathway. Could you walk us through what your residency schedule looked like over those two years, and then what your fellowship time looked like? As background — I'm a residency and fellowship PSDP co-program director, so I'm always interested in hearing about career trajectories, and in helping our listeners understand what these different tracks look like in practice.

[06:16] Chris Thom: These are important decisions for trainees to think through carefully. Normally it's three-and-three — three years of residency followed by three years of fellowship for most pediatric subspecialties. The Accelerated Research Program (ARP) is one of the Accreditation Council for Graduate Medical Education (ACGME) pathways that compresses all residency requirements into two years, which then gives you four years of fellowship. Nothing is actually accelerated in terms of total training time — it just gets you into fellowship faster.

That is in contrast to the Integrated Research Pathway (IRP), which essentially takes a year out of residency to do research. I chose the ARP because I was confident I could identify the specialty I wanted to pursue in a timely fashion. The ARP is the most time-intensive option in that regard. That said, I was motivated by the fact that it would get me into fellowship sooner and open up significantly more protected research time — time that isn't complicated by backup calls and the many clinical demands that come with residency.

Compressing training into two years of residency made for a whirlwind experience. Things have changed a lot at CHOP since then, but at the time I was on call roughly every fourth night for most of the year — it was a lot. That said, I believed it was the right track for me, and it paid off in fellowship. Here, there were no additional clinical requirements beyond what's standard — I spread them over four years and even front-loaded my clinical schedule so that by my second year of fellowship I was covering roughly eight weeks of clinical service. That gave me substantial protected time in the lab to get things in place and launch an independent career.

[09:15] Misty Good: That's fantastic. We're so glad you chose neonatology — you could have gone straight into hematology and fast-tracked right into it. So thank you for ending up in our field.

[09:28] Chris Thom: I was genuinely thankful that the neonatology field was receptive to that. Not all intensive care fields are supportive of trainees coming in with that kind of background. Interestingly, it was near the end of my PhD that I first met Heather French and Scott Lorch through the leadership of the neonatology program here. And I had near-peer mentorship through Scott Gordon, who was a few years ahead of me at Penn in the MD-PhD program and went through residency before me. Getting to observe his experience and learn from his path was really valuable.

[10:16] David McCully: This is a topic I'd love to dedicate a whole episode to someday — just the different training paths and what each one really looks like in practice. There are so many follow-up questions. I imagine that staying at the same institution across residency and fellowship was genuinely beneficial — you were able to build momentum rather than starting over at each step. If you'd moved institutions at each transition, it probably would have been much harder to get things lined up.

[11:01] Chris Thom: We all have some revisionist history about our own trajectories — it didn't have to work out this way. My co-resident John Erickson, for example, did the ARP, completed two years at CHOP, and then left for fellowship at Cincinnati. He's done great. I think the honest takeaway is that you make the best decision you can with the information you have at the time. I pursued neonatology because I loved it clinically. The main pushback I received along the way was: "Your research is all in hematology — how does that fit?" And my answer was simply that babies have blood, babies need blood, and they receive a lot of transfusions. What did I know as a resident or fellow about how that research would eventually connect to the clinical questions I'd be working on? It turns out that the genetic and basic science lens I had — the GWAS work — led me organically to neonatal platelets and platelet transfusion biology.

[12:46] David McCully: Could we go back to your PhD for a moment? It sounds like you were investigating the genetic mechanisms driving blood cell development — is that right?

[13:04] Chris Thom: Exactly. Mitch Weiss's lab knows everything about red cell formation — tissue culture models, mouse models, fetal liver models, all of it. GWAS was in its early days when I was a graduate student, but the concept was coming into focus. Eugene Condras, who was a few years ahead of me in the lab, was very interested in thalassemia and identified proteins related to globin turnover and the pathogenesis of beta-thalassemia. I was looking at a range of targets, many of which were implicated in red cell trait variation, and that's where the genesis of my PhD project emerged: finding that the gene TRIM58 — or single nucleotide polymorphisms (SNPs) at the TRIM58 locus — influences red cell count and red cell size and shape in the general population.

Nobody knew anything about TRIM58 at the time, so we did cell and molecular biology to characterize what that gene actually does. That work gave me insight into GWAS, solid grounding in molecular biology, and familiarity with the hematology model systems — mouse models, cell culture — that my lab still uses today. Importantly, it piqued my interest in genetics. At the time I had no computational skills whatsoever, other than being able to look at a paper, notice a locus over TRIM58 in a supplemental figure, and then go to a geneticist and ask: "What does a p-value of 1×10⁻¹⁰ actually mean in a GWAS context?" That was what drove me, after completing my PhD, to learn much more about computational biology during residency and through my postgraduate work.

[15:43] David McCully: Got it. Misty, did you want to follow up on that?

[15:49] Misty Good: Yes — the field evolves constantly, and there are always new tools coming along. I know that in your more recent work you've embraced single-cell sequencing and various computational analyses. I'm wondering if you could walk us through your mentorship path, the collaborations you've built along the way, and how you've acquired skill sets you didn't start with — and then, as a principal investigator (PI) now, how you stay current.

[16:32] Chris Thom: It always feels like treading water — you learn something and then it's obsolete almost immediately. A good example: my PhD was in Mitch's lab, which knows everything about red cell formation. But it turned out that TRIM58 is an E3 ubiquitin ligase that binds to dynein, a molecular motor protein. All of the molecular biology I ended up doing was about dynein and molecular motors — which was entirely outside anything his lab had done before.

[17:29] Chris Thom: I was staring at a result I didn't know how to approach. I made a cell line, did a pull-down to identify binding targets, and all the hits came back as dynein components — a massive molecular complex. We looked at each other and said: I suppose that's where this is going. So I looked around campus for people who study molecular motors and microtubules, found Erika Holzbaur — a world expert in the field — and sent her a cold email. She agreed to hear me out, and she remains one of my favorite people on this campus. She was extraordinarily helpful with imaging techniques and with the particular intricacies of dynein that I never would have navigated alone. They had all the reagents and all the expertise.

That experience shaped my philosophy as a PI. Every time we get a new result, there's always some new frontier. I start by looking locally — who on campus has relevant expertise, because being in the same room as people is genuinely productive — and then expand outward as needed. Now we venture into computational biology and statistical genetics, and it feels like every person in my lab has their own niche and their own set of collaborators. No single mentor could cover all of it, but between local colleagues and external partners, we make it work.

[19:50] Misty Good: I love that. Team science makes everything go faster and more enjoyable.

[19:58] David McCully: Absolutely. One of the most motivating parts of this work is getting to meet new people, learn about their science, and build something together that neither of you could have done alone. You're also often opening doors for your collaborators — a different perspective or technique can enable entirely new experiments for them. It's a genuine two-way street.

On that note — can you say a little about how molecular motors are involved in blood lineage development? What did you learn from that work?

[20:39] Chris Thom: Molecular motors are involved in virtually every cell and process in the body, so they hadn't received much attention in blood cells — partly because erythrocytes are anucleate. But what we found, to our genuine surprise, is that erythrocytes may be the only cell in the body that lacks dynein. It turns out that TRIM58, an E3 ubiquitin ligase, comes on and degrades dynein. What that enables is a shift in the push-pull balance: without dynein pulling toward the minus end, a host of kinesins can push in the other direction — and red cells need to push their nucleus out in order to enucleate.

That was a difficult thing to demonstrate at the molecular level, but using tools like ImageStream, we were able to show that when you eliminate TRIM58, the nucleus is less well-polarized and cells have trouble completing enucleation. It's a remarkable example of repurposing very canonical cytoskeletal machinery for a highly specific and unique biological purpose. From a broader scientific perspective, it reinforced for me that blood cells do this kind of thing constantly — there are only so many proteins and mechanisms available across all our cells, and what makes erythrocytes, platelets, and megakaryocytes each behave the way they do are these fascinating molecular adaptations.

[22:38] Misty Good: I love the passion that comes through when you talk about the science. That's so important for our listeners who are setting out on this career path — doing work that genuinely excites you and gets you out of bed every morning matters enormously.

[23:00] David McCully: So how did you then transition to platelet biology? I can see clearly how you built the skill set and interest in blood lineage development, but how did you make that pivot?

[23:24] Chris Thom: There's a somewhat unglamorous reason for it. At each stage you need to carve out your own identity, and I noticed that many people trained in red cell biology eventually switch lineages. With so many outstanding investigators already in the erythropoiesis field, I honestly asked myself: how do I find a unique niche here? Pivoting to platelets and megakaryocytes seemed like a reasonable answer.

Beyond that, there was a more substantive motivation: I wanted to deepen my understanding of GWAS and genetics. Even toward the end of medical school, I sent a cold email to Ben Voight, a statistical geneticist at Penn who is the principal investigator on major diabetes GWAS studies — someone who has been in the field for a long time and discovered key principles of population genetics. Out of genuine generosity, he took me on as a postgraduate trainee and taught me to code in computational biology at a foundational level, and then the nuts and bolts of genetics and GWAS methodology.

With that general focus on blood biology and a sense that I should move away from red cells, we initially focused on platelet biology. My project with Ben ultimately spanned residency and all of fellowship — building computational skills and statistical genetics knowledge to bolster the analytical backbone of what I was doing. My PhD project had always had this black box at its center: I didn't really understand how the GWAS hit came to exist. That question was the real driver of this project and became a productive mode of discovery through fellowship.

[25:59] Misty Good: Can you talk about how you took that fellowship work and transitioned it into a grant — specifically a K99/R00? Maybe you could explain that funding mechanism, how you decided to pursue it, and how it set up your independent lab.

[26:30] Chris Thom: Right — because the clock starts ticking as soon as you enter fellowship. What I tell all my trainees, and anyone who'll listen, is a stupidly simple framework: you need a paper, then a grant, then a job. None of those steps is easy, and there's an enormous amount of luck and timing involved. But having come in with some momentum — having already met Ben Voight and developed some foundation in machine learning and statistical genetics before fellowship started — meant I wasn't starting from scratch.

We put together a paper combining statistical genetics, machine learning, and induced pluripotent stem cells (iPSCs), and I submitted a K08 — which was rejected. That was actually a great learning experience. The most useful feedback I got from the study section was essentially: you seem like a promising candidate, but this is a poorly written grant. Learn how to write one. So I did.

Fortunately, in the interim I discovered a K99/R00 pilot mechanism through the National Heart, Lung, and Blood Institute (NHLBI) specifically designed to support physician scientists in the field of blood science. That was a significant stroke of fortune, because I had never seriously considered the K99/R00. It's an incredibly competitive mechanism in most applicant pools. But this pilot offered something particularly attractive: up to five years of K99 support followed by three years of R00 — a longer runway than the standard mechanism. I had submitted it almost in parallel with my revised K08, more as an exploratory move than with strong expectations, and was fortunate to receive it.

[29:31] Misty Good: What stage in your career was this? You had a four-year fellowship — was this during that window?

[29:40] Chris Thom: I submitted the K08 at the beginning of my third year of fellowship. The study section saw it quite differently from how the scientific community around me had responded, which was jarring. But I tell every trainee: you have to try early. About nine months to a year later, as I was starting my fourth year, I tuned up the K08 based on reviewer feedback and resubmitted — and it scored well. And in that same period, the K99/R00 pilot came through. Being able to go on the job market with a strong score and the expectation of receiving a K99/R00 is a meaningful advantage when asking for a faculty position.

[31:26] David McCully: Can you talk about how you actually found that opportunity? I think a lot of people in training know they're going to pursue a K, but they don't always go looking beyond the most obvious mechanism. Was your mentor steering you toward it, or did you find it another way?

[31:54] Chris Thom: The first I heard of it was word of mouth. I was presenting to a hematology group on campus, mentioned where I was in fellowship, and someone said, "You should look into this." Then I did. The further I get into an independent career, the more I realize I still probably don't spend enough time on the NIH website actively looking for opportunities — it's genuinely hard to navigate. But what I've learned is that if you can align your grant with a funding mechanism that is actively looking to receive your type of application, you're in a much stronger position. I now try to spend more time on the NIH websites and to have conversations with program officers about what's available. That's actually what I learned directly from the program officer on this K99 — reach out and talk to them.

[32:56] Misty Good: And you can sign up for weekly emails from the NIH that deliver new funding announcements to your inbox every Friday. That way opportunities come to you rather than requiring you to remember to search.

[33:16] Chris Thom: I appreciate that — I will absolutely do that.

[33:19] Misty Good: It really did change your whole trajectory, finding that mechanism serendipitously. That's remarkable.

[33:39] David McCully: It would make a great dedicated episode — the different pathways to becoming a neonatology physician scientist, paired with a deep dive into funding mechanisms. NIH is the obvious starting point, but there are so many other sources now. It would be valuable just to share ideas and learn from each other.

[34:01] Chris Thom: I also applied for the Burroughs Wellcome Fund — another excellent grant mechanism .

[34:14] David McCully: Should we get into what you're working on now? I'm really curious to hear how you've managed to maintain a basic research program while also doing clinically relevant and translational work in platelet biology and transfusion science. Can you start by describing your basic research focus, and then we can move to the translational work?

[34:49] Chris Thom: In terms of serendipity and mentorship — when I was applying for fellowships, I happened to meet Martha Sola-Visner at Boston. That relationship and collaboration has made most of what we do in my lab possible from a platelet biology standpoint. She has been at the forefront of the idea that neonatal platelets are biologically distinct from adult platelets, and that transfusing adult platelets into babies may be detrimental to their health, for a long time now.

Several years ago, Martha, Patty Davenport, and I, along with a number of other collaborators, had the sense that platelet biology in an anucleate cell must be entirely governed by proteins and post-translational mechanisms. There were decades of research showing that neonatal and adult platelets respond differently to environmental agonists — adult platelets are far more readily activated and degranulate more robustly than neonatal platelets. By applying newer mass spectrometry techniques, we were able to systematically profile the proteome and phosphorylated peptides that are shared and distinct between adult and neonatal platelets, and begin making sense of what underlies those differences.

Having that basic biological foundation — understanding the specific differences in proteins and signaling pathways — has facilitated both clinical and translational change in a way that a clinical trial finding alone could not. The PlaNeT-2 trial demonstrated harm, but many people asked: how could that be true? What's the mechanism? Once we could point to granular molecular differences between adult and neonatal platelets — essentially showing that they behave like different species — it became much more intuitive and compelling. People are genuinely alarmed by some of the findings we've put forward: specifically, that adult platelets carry significantly more immune modulators and pro-inflammatory mediators than neonatal platelets. We've now been able to demonstrate, at a very granular molecular level, the proteins and mechanisms that underlie the differences in platelet activity and degranulation between the two populations.

[38:24] Misty Good: That's so fascinating — especially when a clinical trial drives a field-changing finding and everyone wants to know the underlying mechanism. Your work really speaks to that.

[38:45] Chris Thom: The timing was fortuitous. Getting the right people and the right technologies together at the right moment made those findings possible. What I hadn't anticipated was that basic science could function as a tool for changing minds — using molecular biology to reframe how clinicians think about what they're doing at the bedside.

One of the parallel questions that arose from PlaNeT-2 was whether the harm was partly attributable to the dose — 15 mL/kg — or to the pace of transfusion, which was administered over 30 minutes in non-bleeding neonates. A local initiative here in Philadelphia took that on directly: could we reduce harm by using a lower threshold and a more conservative approach to administration, even beyond what PlaNeT-2 had tested? In those discussions, I found that pointing to specific molecular differences in the platelet proteome — rather than citing trial data alone — was consistently more influential in motivating clinicians to rethink their practice.

[40:32] David McCully: There's probably still enormous variability even within neonatal platelets, let alone between neonates and adults. Having molecular tools to understand what's driving these observations is very helpful. And it sounds like it's also opening a new door — what's the alternative to adult platelet transfusion?

[41:10] Chris Thom: Exactly — that's what this work is spurring. We now have some molecular handles to think through: how do we coax an adult platelet to behave more like a neonatal platelet? With some understanding of the underlying molecular machinery, we have identifiable targets. And there is now considerable expertise here in Philadelphia and elsewhere in RNA delivery and cell modification using lipid nanoparticles and related techniques. For transfusion medicine specifically, we're not putting a therapeutic agent into a patient's body directly — we need to modify a bag of platelets, or even more practically, the small volume drawn from that bag to give to a one-kilogram neonate. That is now achievable. We are exploring those strategies: whether it's the kinase machinery governing activation and degranulation, or some of the key immune mediators, we can modulate the levels of those proteins to coax adult platelets toward a more neonatal-like physiology. That's probably the nearest-term path to a practical clinical intervention — though it will still be years before this can be translated to a product coming from a blood bank.

Beyond that, there are exciting opportunities to think about entirely novel transfusion products designed specifically for babies. We have a collaborator in Japan — Koji Ito — and a company called Megakaryon that manufactures in vitro-derived platelets and has completed a first-in-human trial under an emergency use framework. For years, the field has struggled with how to take human induced pluripotent stem cells (iPSCs), differentiate them into megakaryocytes, and then produce platelets at any translational scale — the pro-platelet shedding process is extraordinarily inefficient in tissue culture. Koji's team circumvented that using a bioreactor-based turbulent flow system and can now manufacture units of in vitro-derived platelets at meaningful scale.

There are compelling reasons to think about this specifically for babies. Any cell you're producing through this process can be modified — you can make the platelets hypoimmunogenic, you can delete the specific proteins that are problematic in adult platelets directly from the genome. And importantly, every iPSC-based platform that drives differentiation toward any blood lineage is essentially recapitulating fetal development. So there is real reason to think that the platelets Koji is producing may be neonatal-type platelets by default. We're exploring that as an avenue. And to be fair to him, there are already many compelling reasons to develop in vitro-derived platelet products — Japan and many other countries are facing real blood supply limitations. Our field of neonatology isn't always top of mind in those conversations, but the biology may align very naturally.

[46:08] David McCully: That's really exciting. You've built this basic science foundation, come to understand the molecular mechanisms of why adult platelet transfusion can harm neonates, and now that knowledge is enabling entirely new in vitro strategies for developing tailored transfusion products. Do you imagine staying primarily in basic science — understanding the genetic mechanisms of platelet lineage developmental biology — or moving toward more clinically translational research, or continuing to do both?

[47:22] Chris Thom: That's an evolving question. If I'd listened to my mentors more closely, I'd probably have spread myself less thin. But every project in my lab is driven not just by me — there are trainees and collaborators pushing each one forward, and my contribution to any given project is often a relatively contained piece within a larger sphere of what we're reasonably competent at. Then it's a matter of talking to people who have the expertise and technologies we don't — for example, I sit next to the team that runs our human pluripotent stem cell core , and they help us generate cells and made the introduction to Koji. Three years from now, the portfolio of projects in my lab will probably look quite different. These things evolve largely based on opportunity and on building from wherever we have momentum.

[48:46] David McCully: Thanks, Chris. This is really exciting work.

[48:49] Misty Good: It's remarkable to think about changing not only how babies receive platelets, but potentially redesigning what those platelets are from the ground up.

[49:05] Chris Thom: It does feel that way. I've been very fortunate to meet the right people at the right time and get into the room to have these conversations. I'm often the only neonatologist present, and that perspective is genuinely valuable — I can point out things like: we don't actually need a full unit of platelets for a one-kilogram neonate. If we can make the right volume, that's actually enough.

[49:41] David McCully: That's one of the most exciting dimensions of being a neonatology physician scientist — building bridges between people who don't normally interact, and advocating for a patient population that often goes unconsidered in broader scientific conversations. Because of our clinical perspective, because we take care of these babies in an extraordinarily vulnerable period of their lives, we bring a different lens to the science and to clinical medicine. That's a remarkable position to be in, and hopefully people listening will be inspired to pursue these questions through this career path as well.

We usually finish by trying to get a glimpse of who you are outside the lab. Your research group sounds exceptional — is there anything you all do together that's fun? Team outings, shared interests, anything like that?

[50:54] Chris Thom: My lab is awesome. We do team outings regularly. We've been bold enough to go paintballing — which could have gone horribly wrong, but my first two graduate students joined the lab shortly after, so perhaps it helped. We've since graduated to escape rooms, and I think laser tag is next. Getting together outside the lab, actually socializing — it makes a real difference. Graduate students, postdocs, undergraduate and graduate students from Penn and beyond — everyone knows each other as people, not just as colleagues in the pipetting room.

[51:42] Misty Good: Completely agree. Getting out of the lab together and seeing each other in a different context does so much for a team. And do you have any words of wisdom for early-stage investigators or trainees thinking about pursuing the physician scientist path?

[52:06] Chris Thom: Some of the best advice I received was simply to keep an open mind and keep your eyes open. I thought I was headed down a clearly defined tunnel and pivoted — and I'm genuinely grateful I didn't box myself in. I'm very happy to be a clinical neonatologist, and that joy comes partly from not having foreclosed options prematurely.

In terms of opportunities more broadly — whether for grant funding or research projects — I've benefited enormously from being at CHOP and Penn, surrounded by dynamic speakers and remarkable science across disciplines. I think both of you have come to give research conference talks here, actually. There's a lot of exciting work happening out there that can expand the technologies and platforms you use, but also the way you think about physiology and disease. Staying open to that, and encouraging trainees to stay open to that, is something I try to consistently do.

[53:12] Misty Good: That's wonderful. This has been such a thoughtful and inspiring conversation. Thank you so much for sharing your science and your career journey with us.

[53:25] Chris Thom: Thank you for the invitation. It's been a great conversation.

[53:28] David McCully: Thanks, Chris — I learned a great deal today. It sounds like we'll see each other at PAS (Pediatric Academic Societies), so we'll get to talk again there. Thanks everyone for tuning in to At the Bench, and we'll be back soon with another episode. Take care.

[53:50] Misty Good: Take care, everyone.