#311 - 🔬 The Placenta Holds the Answers: A Researcher’s Perspective

Hello Friends 👋

In this episode of At The Bench, Drs. Misty Good and Betsy Crouch speak with Dr. Stephanie Gaw, a maternal-fetal medicine specialist at UCSF, about her path to becoming a physician-scientist and her translational research on placental infections. Dr. Gaw shares how early lab experiences, time in the Peace Corps, and a pivot from infectious disease to OB-GYN shaped her focus on maternal immunity and global health.

The conversation covers Dr. Gaw’s work on sepsis in pregnancy, COVID-19 and RSV vaccine responses, and congenital infections like syphilis. She also discusses her approach to building and managing a large placental biorepository, and the importance of thoughtful sample collection for reliable research outcomes. The episode includes practical insights on balancing clinical duties with research, the benefits of peer mentorship, and how clinical observations can drive lab-based investigation.

This discussion offers a clear look into the realities and rewards of bridging bedside observations with bench research in maternal-fetal medicine. It’s a valuable listen for early-career physician-scientists and anyone interested in the complexities of immunology, placental biology, and perinatal infection.

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Short bio: Dr. Stephanie Gaw is a perinatologist, an obstetrician who specializes in high-risk pregnancies and prenatal diagnoses of disorders or complications. She has particular expertise in prenatal ultrasound. Dr. Gaw's research interests include placental malaria, the genetic evolution of Zika virus and vaginal birth after cesarean delivery, as well as as well as the rate of preterm birth in twin pregnancy. Gaw earned her medical degree at Albert Einstein College of Medicine, where she also earned a doctorate in microbiology and immunology. At UCSF, she completed a residency in obstetrics and gynecology, followed by a fellowship in maternal-fetal medicine.

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

Placental malaria induces a unique methylation profile associated with fetal growth restriction.

Ozarslan N, Mong C, Ategeka J, Li L, Buarpung S, Robinson JF, Kizza J, Kakuru A, Kamya MR, Dorsey G, Rosenthal PJ, Gaw SL.Epigenetics. 2025 Dec;20(1):2475276. doi: 10.1080/15592294.2025.2475276. Epub 2025 Mar 6.PMID: 40051167 Free PMC article.

Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination.

Matsui Y, Li L, Prahl M, Cassidy AG, Ozarslan N, Golan Y, Gonzalez VJ, Lin CY, Jigmeddagva U, Chidboy MA, Montano M, Taha TY, Khalid MM, Sreekumar B, Hayashi JM, Chen PY, Kumar GR, Warrier L, Wu AH, Song D, Jegatheesan P, Rai DS, Govindaswami B, Needens J, Rincon M, Myatt L, Asiodu IV, Flaherman VJ, Afshar Y, Jacoby VL, Murtha AP, Robinson JF, Ott M, Greene WC, Gaw SL.JCI Insight. 2022 Jun 22;7(12):e157354. doi: 10.1172/jci.insight.157354.PMID: 35579965 Free PMC article.

Gravidity influences distinct transcriptional profiles of maternal and fetal placental macrophages at term.

Ozarslan N, Robinson JF, Buarpung S, Kim MY, Ansbro MR, Akram J, Montoya DJ, Kamya MR, Kakuru A, Dorsey G, Rosenthal PJ, Cheng G, Feeney ME, Fisher SJ, Gaw SL.Front Immunol. 2024 Jun 26;15:1384361. doi: 10.3389/fimmu.2024.1384361. eCollection 2024.PMID: 38994356 Free PMC article.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy.

Prahl M, Golan Y, Cassidy AG, Matsui Y, Li L, Alvarenga B, Chen H, Jigmeddagva U, Lin CY, Gonzalez VJ, Chidboy MA, Warrier L, Buarpung S, Murtha AP, Flaherman VJ, Greene WC, Wu AHB, Lynch KL, Rajan J, Gaw SL.Nat Commun. 2022 Jul 30;13(1):4422. doi: 10.1038/s41467-022-32188-1.PMID: 35908075 Free PMC article.

Association of Prenatal Ultrasonographic Findings With Adverse Neonatal Outcomes Among Pregnant Women With Zika Virus Infection in Brazil.

Pereira JP Jr, Nielsen-Saines K, Sperling J, Maykin MM, Damasceno L, Cardozo RF, Valle HA, Dutra BRT, Gama HD, Adachi K, Zin AA, Tsui I, Vasconcelos Z, Brasil P, Moreira ME, Gaw SL.JAMA Netw Open. 2018 Dec 7;1(8):e186529. doi: 10.1001/jamanetworkopen.2018.6529.PMID: 30646333 Free PMC article.

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

Misty GoodWelcome back to At the Bench, the Physician Scientist podcast of the Incubator. I'm Misty Good, the Division Chief of Neonatology at UNC Chapel Hill, and I'm excited to be co-hosting today with Dr. Betsy Crouch. Betsy, would you like to introduce yourself?

Betsy Crouch

Of course. Thanks everyone for joining us. I'm Betsy Crouch. I'm a neonatologist, a neuroscientist, and a vascular biologist at the University of California, San Francisco. I'm very pleased today that we get to interview my friend and colleague—my co “up in the middle of the night taking care of moms and babies” collaborator—Dr. Stephanie Gaw. Dr. Gaw, would you please introduce yourself?

Stephanie Gaw

Thanks for the invitation to chat with you today. My name is Stephanie Gaw. I'm an Associate Professor of Maternal-Fetal Medicine at UCSF, and my lab focuses on placental infections and maternal-fetal immunology.

Betsy Crouch

Thank you so much for joining us. I'm really excited to talk about all the different agents and infections you study, many of which are rising in incidence among both pregnant individuals and the babies we care for. This is such important work, and we’re thrilled to dive into it with you.

Let’s start with your career trajectory. Did you always know you wanted to be a physician-scientist? How did you decide to specialize in maternal-fetal medicine?

Stephanie Gaw

Oh gosh, it’s such a roundabout story. I’ve actually been talking about this a lot recently because my oldest daughter is graduating from high school and going through the process of choosing a major. I told her that at her age, I had no idea that the job I have now even existed.

I went to Berkeley for undergrad and majored in molecular and cell biology—though I still don’t really know why. That’s when I got my first taste of lab work. I did my senior research thesis in an immunology lab with Dr. Neelak Shastri, studying basic immunology like MHC and antigen processing.

But during college, I decided I wanted to join the Peace Corps. So I didn’t apply to medical school or have a clear career plan. I just knew I needed to get away and experience the world, to understand how most of the world actually lives. So after graduating from Berkeley, while many of my friends were applying to med school, I joined the Peace Corps and served in Honduras for two and a half years. Back then, there were no cell phones, and email was still very rudimentary, so my good friends wrote me real letters. One of my friends, who had gotten into an MD-PhD program right out of high school, told me about it for the first time in one of those letters.

While I was in Honduras, I debated between going into medicine and research or pursuing something in public health. But eventually, I realized I wanted to do biomedical research on topics that were directly relevant to the developing world. That’s what drew me to infectious diseases and global health.

So I applied to MD-PhD programs—because my friend recommended them and he had a great experience—and ended up at Albert Einstein College of Medicine in the Bronx. I was drawn to the program because of its strong departments in immunology, infectious disease, and parasitology. It's one of the most globally diverse academic medical centers in the country, seeing many immigrants, travelers, and people returning from visits abroad. They treated all the rare and unusual infections.

I joined a malaria lab there, led by Dr. David Fidock, who is now at Columbia. I studied drug resistance in malaria—very molecular parasitology. I basically made transgenic parasites with different mutations in drug resistance genes to see how they'd respond. It was very lab-based, but it got me into infections and infectious diseases.

Betsy Crouch

Do you have any crazy stories from your time in the lab?

Stephanie Gaw

God bless everyone who works in malaria labs, but I never want to grow that parasite again. We had to do it every week, and if you went anywhere, someone else had to take care of your cultures. I decided then—I'll always collaborate with people who grow it, but I won't culture the parasite myself. It’s very finicky. You have to be really precise.

Misty Good

Can I ask a question before you go on? Because I think this is really important for everyone who's thinking about research and trying to pick a project. How did you choose a malaria lab?

Stephanie Gaw

I think I chose the lab because of the rotations. We had to do three, and I rotated through an HIV lab first—that was fun. Then came the malaria lab, and finally a TB lab. I just clicked most with my malaria lab mentor. We had similar personalities, and I felt the least nervous around him. I could ask “dumb” questions, and he’d ask me some too. It just felt relaxed and comfortable.

Scientifically, I still think Plasmodium is one of the most fascinating pathogens out there. The life cycle is incredibly complex, with different genes expressed in each stage. That complexity is part of why it’s had such a devastating impact on humans over millennia. I was also deeply committed to global health, and malaria is a disease that disproportionately affects the poorest populations in the world.

So I did my PhD, and originally thought I’d go into medicine and infectious diseases—follow that traditional physician-scientist track. But after I defended, my first clinical rotation was OB-GYN, and I loved it. I thought maybe I just liked being out of the lab. At that point, I had a one-year-old, so I felt comfortable in that space. But then I did a medicine rotation, and I was cranky all the time. I just didn’t enjoy it. So I thought, maybe pediatrics? Maybe Peds ID? But then I did a pediatric rotation, and I couldn’t take care of kids—it just didn’t fit.

One of the best pieces of advice I ever got came from a visiting speaker in the MD-PhD program. She said: pick your clinical specialty based on the patients you want to take care of, not the research you want to do. Research can take you anywhere—you don’t know where the science will lead—but you can’t change the patients. And if your heart is in research, and you don’t enjoy clinical care, you might end up resenting that part of your work. So, pick patients you genuinely enjoy caring for. That way, you won’t hate half your life—or however much of your time is spent on clinical work. That stuck with me.

I couldn’t see myself doing medicine or peds, so I thought, maybe OB? I talked to my program director and told him I was switching to OB. He said, “That’s great!” Around that time, I think Science or Nature had just published a paper identifying the angiotensin II receptor as a potential mediator of preeclampsia. I thought, “See? There’s real science here.” The more I thought about it, the more it made sense. Maternal-Fetal Medicine (MFM) especially attracted me because it combines all the most interesting aspects of medicine and pediatrics—but in one patient. The medical complications and clinical questions become 10 times more complex, because you're balancing two patients at once. Everything a non-pregnant person might experience—when it happens during pregnancy, it changes. Some diseases specifically target pregnant people. Others might barely affect the parent but have a major impact on the fetus. It’s just a fascinating space.

The pace of MFM made more sense to me, too. I think I’m pretty impatient, and I liked the shorter, more intense nature of OB care. I didn’t do well with chronic illness and long-term management, which is a big part of internal medicine.

Betsy Crouch

Yeah, there’s so much to explore. I think it’s really exciting to have you on—you're our first MFM guest. This podcast focuses on neonatal physician-scientists—or those working in adjacent areas—and I think one reason we’re friends, is because I love picking your brain about how you think through medical and scientific problems. Physician-scientists are a rare breed in MFM, though there are outstanding programs like the RSDP. Could you talk a little about that program and other efforts to cultivate more physician-scientists in maternal medicine?

Stephanie Gaw

No, definitely. I think there are very few physician-scientists in OB in general, and even fewer in MFM. It’s hard to find role models, and it's hard to maintain a job as a physician-scientist in this field. At most institutions, there’s often just one of us—like here, it's just me. So my division leadership doesn’t really know how to support or structure my role. There isn’t a direct mentor within my department who’s followed the same path. The RSDP—the Reproductive Scientist Development Program—that Betsy mentioned is a national K12 program. It's similar to the PSDP.

Betsy Crouch

It is, yeah. I know about it because I was part of the PSDP, and they were looking to collaborate with the RSDP, which makes a lot of sense. I was even invited to speak at the RSDP retreat—though it was during COVID, so it was online. I still have all this RSDP swag, which I really appreciate. It makes me think fondly of my MFM colleagues. As a neonatologist, in the pediatric spectrum, we’re closest to the OB space. I really enjoyed that connection, since we work so closely with our OB colleagues.

Stephanie Gaw

Exactly. The RSDP is an NIH-funded national K12 program, but they also receive supplemental funding from the Burroughs Wellcome Fund and March of Dimes. That helps broaden and amplify their resources. It includes all OB-GYN specialties, and everyone is a physician-scientist. There’s quite a bit of MFM representation, and programs like that are essential, especially in specialties where physician-scientists are so rare. That’s actually how I know most of the physician-scientists in MFM across the country. Either we met during RSDP interviews or we’ve connected through the program over the years. It's been a great network, especially since we’re all applying for similar career development awards, dealing with rejections, starting labs—it’s helpful to have that sounding board.

Misty Good

I think both the RSDP and PSDP really raise awareness about the importance of peer mentorship—especially if you’re the only physician-scientist in your division, like you. It’s so valuable to connect with people going through the same thing or who’ve just been through it. Could you talk more about how early-career physician-scientists can take advantage of those networks and early collaborations?

Stephanie Gaw

It was absolutely instrumental for me. UCSF is an amazing research institution, but as an MFM physician-scientist, I’m the only one here. There are others in different subspecialties, but the clinical demands, skill maintenance, and time balance vary a lot between fields.

During my first two years as faculty, I didn’t really know what I was doing, and neither did my division. For example, while on the RSDP K12, I had 25% clinical time. I was scheduled accordingly, but that meant a clinic here and a clinic there. In MFM, we do a lot of satellite work, so I’d be driving all over. It didn’t make sense. I started talking to friends at other institutions asking “What do you do?” and realized everyone does it differently. Eventually, I started blocking my time. Now I do four clinical days a month, all in one block. I just disappear for those days, then I’m fully back in the lab. Others might do one clinic day per week—like every Monday. It really depends on your lab and research setup.

Breaking up time was inefficient. You end up doing notes the next day, driving around town—it’s a huge time suck. So it’s always helpful, no matter your specialty, to talk with others about how they structure their days and manage time and resources. My division director didn’t have a handbook for how to support a physician-scientist. I didn’t know what to ask, so I just did whatever I thought I should do. It took a while to figure out what worked.

Misty Good

When you're driving around to all those places and doing your clinical work, did you ever have clinical observations that inspired your research?

Stephanie Gaw

One of the most fun parts of my job is that OB-GYN has so many unanswered questions. Honestly, we’re like 20 years behind internal medicine in terms of evidence-based practices. There’s a lot of dogma—just doing things the way they've always been done—and we’re often hesitant to change. So when you step back and really ask, “Why do we do this?” or “How do we explain this to patients?”—there are so many unknowns. That’s where I feel my secret power as a physician-scientist comes in. I can put on my scientist hat and think, “How do we answer this question? Can I study it in the lab? What samples do I need?” That part has been really exciting. Early on, you don’t realize this potential. You're comparing yourself to amazing clinical mentors who know everything and top-tier scientists using cutting-edge technology. But as a physician-scientist, I’m in the middle—I don’t know everything, but I can translate between the bench and clinical care.

Lately, we’ve been working on sepsis/fever in pregnancy and the inflammatory response to infection. Most existing research focuses on patients who develop sepsis and deliver while actively septic, and those babies are often very sick and preterm. I remember a patient who was septic and in the ICU for a few days with pneumonia. She recovered, was being discharged, and asked me, “Is everything going to be okay with my pregnancy?” I said, “Oh yeah, you’ll be fine.” Then I walked out of the room and thought, “Wait, I think we just lied to her.” Because we actually don’t know. There were no studies on patients who have sepsis during pregnancy, recover, and then go on to deliver later.

So that inspired us to dig into the data. We looked at epidemiological studies and started collecting blood samples of patients who had a septic event during pregnancy. In one study using the California Birth Registry, we found increased neonatal risks—even after adjusting for gestational age. Things like retinopathy of prematurity showed up, which was unexpected. At UCSF, we analyzed 20+ years of data and saw that patients who were admitted for sepsis, discharged, and later delivered, they had higher rates of growth restriction and hypertensive disorders—suggesting more chronic effects. Now, I have a fellow in the lab working on collecting non-transmitted infections—like pyelonephritis or kidney infections during pregnancy. In these cases, the baby doesn’t get the E. coli infection, but the mother can get really sick. We’re currently doing spatial transcriptomics on the placentas to see how an inflammatory insult in the middle of pregnancy impacts placental development throughout gestation and ultimately affects pregnancy outcomes.

Betsy Crouch

What cool stories. I’ll add that one of the ways Stephanie and I know each other is through our shared use of a spatial transcriptomics machine. It’s been a great collaboration. I’m primarily interested in vascular cells in the brain and CNS, and Stephanie’s focused on those in the placenta. Now we even have two postdocs working together, which has been really helpful for comparing vascular phenotypes across different organs and physiological states. It's a great example of how clinical overlap can lead to research discovery.

Stephanie Gaw

Yes, and when you’re learning a new technology—like spatial transcriptomics—it’s helpful to work through it with someone you trust. Nobody really knows exactly what they’re doing at the start, so being able to think things through together is invaluable.

Betsy Crouch

Exactly. There's been so much fascinating work emerging in spatial transcriptomics. We do need to move beyond just “looking at dots,” where we’re primarily seeing the dominant cell type in a tissue, and start digging deeper. Really a much more targeted approach that people are doing in different ways. But yeah, I found that to be very exciting.

Misty Good:

From an immunologic perspective—what is there? And for the placenta in particular, there's so much unknown. We know what it does functionally, but in the setting of infection or maternal sepsis, as you mentioned, what do we not understand? What immune cells are there? What are they doing? I think the placental response to infection and how that affects the baby is critically important.

Stephanie Gaw:

Yeah, and I think a lot of the work fundamentally struggles with the same issue in placental translational studies: you don’t get the placenta until the end. You don’t know what happens early. And if there is a miscarriage or an early termination, those samples don’t tell you what the eventual outcomes would have been. So we’re always trying to make inferences from the endpoint. I don't have a perfect solution to overcome that, but just keeping that limitation in mind is crucial.

We recently published an epigenetics paper on placental malaria, which is the leading cause of fetal growth restriction worldwide. Here in the U.S., of course, we have fetal growth restriction that’s not malaria-related. Epigenetic modifications of the placenta have been associated with fetal growth restriction in developed countries, but no one had studied it in the context of malaria. So we looked at fetal growth restriction with and without malaria, using cohorts from here in San Francisco and from Uganda. Interestingly, the epigenetic changes—specifically the differentially regulated genes and CpG sites—were totally different between the two cohorts, even after accounting for location and environmental factors. It suggests the mechanisms of growth restriction are fundamentally different between malarial and non-malarial cases, even though the clinical end result looks the same. But the challenge is, we can’t say what caused what. Did the epigenetic changes cause the growth restriction? Or are they a response—compensatory mechanisms by the placenta after growth restriction has already started? We just don’t know. We can’t establish causality with just one sample.

Betsy Crouch:

But you could in an experimental model!

Stephanie Gaw:

Exactly. I joke that I spent the first three to four years of my faculty career just collecting interesting samples without always knowing what I’d do with them. But now, one of the things I’m focused on is building a more prospective biobank. For example, we do have patients who undergo chorionic villus sampling (CVS) early in pregnancy. I’d like to start banking those samples because even if complications arise later—or not—we’d have both a beginning and an endpoint from the same pregnancy. That would allow us to look for predictive markers across gestation. It’s a challenging but really intellectually rewarding aspect of placental research. We often only get one time point and don’t know what came first.

Misty Good:

Can you talk a little more about your biorepository? You’ve been collecting samples, and it sounds like you’ve developed something substantial. Certainly, for our listeners, that’s of interest. You mentioned that during the first three years of your faculty position, you were collecting samples—are you doing that now in a more focused way? Or a broader way? Because you never really know where your science is going to take you. So how do you decide what to collect and when to collect at different time points?

Betsy Crouch:

This is Steph’s superpower. I mean, what a valuable resource. And the fact that she had the vision to start banking these samples—now you’ve got this placental biobank with... how many cases?

Stephanie Gaw:

Oh, we have thousands. When I first got into this, I was a malaria researcher. We cultured parasites—very lab-based work. When I came to residency at UCSF, I worked with Susan Fisher, a placenta biologist. And by luck, she had a graduate student who had been interested in placental malaria and had collected samples from the Democratic Republic of Congo. They were all symptomatic malaria cases at delivery, but there was almost no clinical data. We did some basic immunohistochemistry for macrophage markers—just beginning steps. But that was when I realized that I couldn’t do any meaningful molecular testing on these samples. At the time, spatial transcriptomics wasn’t even possible on FFPE samples. Also, there just wasn’t enough associated clinical information. We only knew the gestational age, roughly, and that the patient had malaria.

And so that's when I started thinking about collecting samples that would be really useful in translational research. I do think this is one of the major problems when you go back and look at all the translational work that has been done in the perinatal medicine field. For example, preterm birth is a classic. A lot of places people will define preterm birth as if you delivered before 37 weeks. But of course, there's a huge difference between spontaneous preterm birth and then preterm birth for some other reason. And they're just grouped together, we don't know, or like labor or non-labor. Like, especially when you're studying inflammation and immunity, like the labor process itself triggers a lot of cytokines, cortisol, and all this inflammatory response that you wouldn't necessarily see in a non-labor patient. And so I think that's when I started to set out and think about how do we want to preserve all these samples. To potentially use for all these fancy experiments that we want to do down the line, whether it's advanced immunology experiments, transcriptomics experiments, either in blood samples or in placenta, and then obviously imaging and all this technology that when I started collecting, I had no idea we'd be able to do.

So I have collaborators that do clinical trials in Uganda malaria. So that's how they're collecting a lot of the malaria samples. But it's always nice to have some sort of domestic connection. So again, because malaria is the leading cause of growth restriction, I'm like, I just started collecting growth restricted babies here of all type. It's like every once in a while. And my selection criteria at the beginning was because it's just me and I had one technician maybe at the time was like, whenever they were available, we grabbed that sample. Over time and I think really actually when my biobank really grew was during COVID. We got a pot of money, you at the beginning of the COVID pandemic, it seems so long ago now, but people are really motivated, I think, to do research and do research quickly and I've gained some experience from the Zika pandemic, collecting exposed samples really quickly and enrolling a cohort really quickly. So we started enrolling these COVID patients. So at beginning it was just everybody with COVID.You know, test deposit for COVID, we collected blood samples at the time of infection, we like isolated plasma, PBMCs like just to be able to do anything, we collected swabs, we collected meconium, stool, we didn't know what we were going to do with them. But I was afraid to not have something. I was thinking about like, what if we want to grow it out? And what if it like the report came out that people in the ICU were COVID positive in their stools. And maybe it gets transmitted that way. Let's collect meconium and maternal stool and we'll see. And we collected everything. And then probably about when the vaccine came out, we started doing that too. Like, oh, maybe we should look at vaccine responses. It was actually a beautiful natural experiment of like the first antigenic sim in humans of this brand new pathogen. We knew exactly when during pregnancy they were exposed, initially the infection, and then with vaccination. Then when the vaccine came out, we realized, my gosh, there's going to be no more COVID negative patients, naive patients. So then we started, we called them unicorns. So then we were like selectively looking for people that said they hadn't gotten COVID and were not vaccinated and like begging them for samples. And now those are like our most precious samples because otherwise everybody else is like COVID serology positive and you don't know how many times they've been exposed.

Over the past five years, that also expanded when the RSV vaccine came out, where we wanted to look at RSV. That's a different scenario in that everybody has baseline immunity to RSV. So you can't look at naive responses, but it really is booster responses during pregnancy. I think we spent probably two years collecting samples. Didn't have the bandwidth to do anything else and then really started digging into a little bit about looking at immune responses, and the most economical and fastest thing to do is look at antibody responses first. So we looked at vaccination versus infection over the course of gestational age. I think these are the closest thing we'll have to infecting pregnant people at a specific time with a novel pathogen: to look at pathogen specific responses. What we found is really interesting: vaccine induced antibody responses are always higher than natural immunity, for some reason. Neutralizing activity is higher in vaccinated responses and antibody transfer is also better with vaccine induced antibodies than naturally induced antibodies. We don't know why, but as far as for vaccine development in the future, know, as we look at more, how more vaccines can benefit not just the mom, but really their baby. A lot of moms won’t vaccinate for themselves, but they will for the baby.

Betsy Crouch

Do you have speculations, hypotheses about why the vaccine-induced antibodies are more easily transferred and have an increased antigenic response?

Stephanie Gaw

I don't know exactly why. My main RO1 right now is looking at placental factors that dictate differential antibody transfer, whether it's different. Also, when we look at epitopes, epitope-specific transfer, there's also a difference in the epitopes that are transferred from mom to baby and a difference for every patient. We're trying to like dig into it a little bit more, whether it's the antibody subtypes that are generated or something else that we don't know anything about. A lot of maternal fetal immunity is hand-wavy, like antibodies go to the mom, or from the mom to the baby, and the babies are protected. We do know that, but how it happens, we don't really know. I suspect it has something to do with the gestational age at the time of exposure. I do think there's something about, know, when you're getting a vaccine, you're otherwise healthy and like generate your body generating antibodies under duress, like with an actual infection, the quality or like the repertoire might be a little bit different, but I don't have anything more intelligent to say about that. That's like the only thing. Like you're totally healthy, you get exposed to a really high dose and it might be a dose response too. A higher inoculum of the vaccine antigen.

Betsy Crouch

Yeah. Well, I think those are brilliant insights. So thanks for sharing. You know, I guess the only other infection that I'm aware of that you study that we haven't talked about is syphilis, which I think is a rising public health problem. I also wanted to take the opportunity to pick your brain on your efforts.

Stephanie Gaw:

I’ve been fascinated by syphilis for a really long time because, one, it’s such an old infection; two, it mostly affects poor people; and three, it’s the “great imitator.” It infects everything. It’s so bad for babies. It infects the placenta, and we don’t really understand what happens. Nobody has studied it extensively in many, many years. They only managed to culture it a few years ago, and there are just a handful of labs that can do it.

We have an R21 grant right now to collect syphilis samples. This is more of a clinical translational study because, diagnostically, it’s impossible to diagnose recurrent syphilis in pregnancy. The consequences are so severe. If you follow the guidelines, for early syphilis you do three doses, and for late syphilis, just one dose. But you can’t really tell, because it’s based on RPR, which is a totally nonspecific antibody test. Even with the most specific antibodies, the diagnosis still doesn’t make sense. So I wonder, why don’t we have a molecular test or something else?

I work in Fresno in the Central Valley, which is one of the syphilis hotspots in California. At the hospital where I work, Community Regional, Fresno County had the second highest number of congenital syphilis cases in 2020. When I wrote my grants, there were about 240 congenital syphilis cases reported to the county. So, you can imagine the number of maternal syphilis cases was even higher. Ninety percent of those delivered at my hospital. Thankfully, those numbers have gone down significantly because the public health department did great outreach and education work. That’s a bit tough for my study, because every time I go to Fresno to work, I still see two or three patients with a potential new diagnosis of syphilis. Are these cases recurrent syphilis? Is it reinfection? Is it adequately treated? Most patients who get syphilis have very complicated lives, so they often can’t get treatment or testing. Very few come in with the classic symptoms. So, the study is to collect samples – and that’s my superpower, collecting good samples – and looking for new diagnostic markers of active and treated syphilis, and hopefully congenital syphilis as well. The way we diagnose congenital syphilis now is even worse than how we diagnose it in moms, because we’re waiting for the mom’s RPR to wash out. So, we want to find new biomarkers that allow faster diagnosis at the time of delivery.

Misty Good:

To expand on your superpower, one of your other grants is the K24, focused on building a translational research career. K24 awards are really important for mentoring the next generation. I’m curious, what are the biggest barriers you see for early career physician scientists trying to bridge basic science and clinical or translational research? And what advice would you give them?

Stephanie Gaw:

I’m so blessed to have the K24. One of the biggest resources in my lab is our huge biorepository. For example, we have about 2,700 placentas from Uganda from a clinical trial we just finished, 800 COVID-positive placentas, and another 300 vaccine-exposed placentas. With such a large collection, we can really answer specific questions and carefully select samples. Whenever we run a big experiment, my lab might get sick of me, but we spend two to three months just on sample selection. I look at it multiple times: Did we think about this? Did we think about that? Molecular experiments are very expensive and complex. If there’s too much clinical noise, or if we didn’t consider a potential confounder like autoimmune disease, then you don’t know what to make of the data. The data can be noisy, and conclusions can be skewed.

The K24 was awarded just a few months ago, but it really helps protect my time so I can focus on mentorship and training future physician scientists about what to consider in sample collection. Bad samples and good samples will both give you data, but only good samples will give you usable data that leads to solid conclusions. You want to be able to answer questions well.

Misty Good:

Your mentees are lucky to have you for sure.

Stephanie Gaw:

It’s really fun. There are new cohorts all the time. For example, Stephanie Cho is a pediatric ICU fellow interested in placentas and pulmonary hypertension, so we’re looking at her placental data. There’s always new stuff. We’re Googling random things like McCune-Albright syndrome and other rare diseases together. That’s the fun part of science—you never know where it’s going to go.

Betsy Crouch:

Yeah, well, we’ve really enjoyed talking with you and learning about a wide spectrum of infections. I feel like I’ve traveled around the world in the last 40 minutes. We like to close with something fun about our guest’s research team. Is there favorite music you listen to while working through placental samples? Any lab traditions you want to share?

Stephanie Gaw:

Gosh, no, it’s a pretty quiet lab. Nobody listens to music. People have headphones on, but there’s no shared music or vibe in the lab.

Betsy Crouch:

That’s different. When I did my PhD, we had a lab CD player and we’d go through options – do we want to listen to Spanish guitar or Modest Mouse? Labs are very international environments, so it was like, are we going to Japan or Argentina or New York today?

Stephanie Gaw:

Now, many labs I walk through are quiet. Everyone’s doing their own thing. Also, open lab spaces echo, so people don’t play music out loud much. We try to do something fun maybe two or three times a year, like a Lands End hike or a picnic where people bring their kids. It’s nice to see people’s families outside the lab. It’s funny when you’ve been around long enough—I’m in my eighth year as faculty—I think we need to do a lab family tree. It starts with one or two people, and suddenly there are so many who graduate from your lab. We invite lab alumni back sometimes, and they bring their kids, who are bigger now. It’s fun to see the growth.

Betsy Crouch:

We had a Center for Fetal Maternal Medicine 10-year anniversary recently, thanks to Tippi MacKenzie and Mary Norton's efforts to build a precision medicine center. Many people brought significant others, kids, even dogs. It was such a beautiful display of friends, families, and animals. It made me think we should do something like that.

Stephanie Gaw:

Yeah, it’s good. You get so immersed in the lab, and lab feels like a family, but you only see part of it.

Misty Good:

Well, Stephanie, we’re so grateful to have you on the podcast. You’re clearly a leader in maternal-fetal medicine and translational research, both locally and globally. As Betsy said, your work is really shaping how we understand immune development, placental biology, and perinatal infections. Thank you so much for sharing your expertise with us today.

Stephanie Gaw:

Thanks so much for the invitation.

Betsy Crouch:

All right, thank you all for joining us, and to our listeners too. We’ll catch you next time on the “At the Bunch” segment of the Incubator podcast. Take care.