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In this episode of That’s Pediatrics, our hosts talk with Thomas Hooven, MD, physician-scientist in Neonatology at UPMC Children’s Hospital of Pittsburgh.
In this episode our experts discuss:
Thomas Hooven, MD, is a physician-scientist at UPMC Children’s Hospital of Pittsburgh with board certification in general pediatrics and neonatology/perinatology. He is the principal investigator of a research program spanning microbiology, bacterial genetics, bioinformatics, and immunology. His current work combines critical care of high-risk infants with basic science and translational laboratory research investigating interactions between microbial pathogens, pregnant mothers, and their babies. His laboratory focuses on understanding infection caused by Streptococcus agalactiae (group B Streptococcus; GBS), an important contributor to newborn morbidity and mortality, and how the neonatal microbiome influences susceptibility to infectious diseases.
Allison “Alli” Williams, MD, is a pediatric hospitalist and is certified by the American Board of Pediatrics. She is a member of the Paul C. Gaffney Division of Pediatric Hospitalist Medicine, medical-surgical co-management team director, and assistant professor at the University of Pittsburgh School of Medicine. Dr. Williams received her medical degree from Herbert Wertheim College of Medicine at Florida International University in Miami, Florida, and completed her residency at UPMC Children’s Hospital of Pittsburgh. Her clinical interests include non-RSV bronchiolitis, febrile neonates, and the enhanced of patient care through medical-surgical co-management.
Sameer Agnihotri, PhD, is director of the Brain Tumor Biology and Therapy Lab and an assistant professor at the University of Pittsburgh School of Medicine. Dr. Agnihotri earned his bachelor’s degree in biology, specializing in genetics, followed by his doctorate degree in medical biophysics, both at the University of Toronto. While there, he used genetic screens to identify novel drivers of glioblastoma, an incurable brain tumor. He subsequently completed his post-doctoral fellowship at the Arthur and Sonia Labatt Brain Tumor Research Centre at the Hospital for Sick Children, in Toronto, and the Princess Margaret Cancer Centre, Division of Neuro-oncology Research, also in Toronto. Dr. Agnihotri’s lab studies pediatric and adult high-grade gliomas.
The Hooven Lab for Neonatal Bacterial Pathogenesis Research | CHP.edu
Neonatal Intensive Care Units | CHP.edu
Group B Strep (GBS) | Centers for Disease Control and Prevention
CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy | NIH.gov
Microbiome | NIH.gov
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Voiceover: This podcast is for informational and educational purposes only. It is not medical care or advice. Clinicians should rely on their own medical judgements when advising their patients. Patients in need of medical care should consult their personal care provider. Welcome to "That's Pediatrics", where we sit down with physicians, scientists, and experts to discuss the latest discoveries and innovations in pediatric healthcare.
Dr. Allison Williams: Hi, I'm Alli Williams, one of the hospitalists here at UPMC Children's Hospital of Pittsburgh.
Dr. Sameer Agnihotri: I'm Sameer Agnihotri, a scientist here at Children's Hospital.
Dr. Williams: And we are so excited today to be joined by Dr. Thomas Hooven. He is one of our physician scientists who is board certified in general pediatrics and neonatology, and also does some amazing lab work that we're here to talk about, with a bacteria by the name of Group B strep. Thanks for joining us today.
So one of the things that we always like to do is just to start with a fun question, usually it's something about Pittsburgh, because we are all Pittsburghers at heart, whether we came here or we were born here.
Dr. Thomas Hooven: Sure.
Dr. Williams: And so my favorite question to ask is, what is your favorite thing to do in Pittsburgh?
Dr. Hooven: Oh. Well, so I moved here with my family in 2019 from New York City, and we've really enjoyed the town, I have an 11-year-old and an eight-year-old. And we love the Carnegie Science Museum.
Dr. Williams: Yes.
Dr. Agnihotri: Wow.
Dr. Hooven: If there's any spot on the map where we've put in the most hours here, as a family, it's there. That's a fabulous place.
Dr. Williams: Could not agree more. And then if you have the membership there too, then you also get the other museums, but we also are avid Science Center fans in my household, so. What a great choice. Now I'm just thinking about the Science Center.
Dr. Agnihotri: I know.
Dr. Williams: But that's not what we're here to talk about.
Dr. Hooven: I haven't gone to, they have those laser shows, and I do want to see that. My kids have gone with their babysitter a couple of times, and those are supposed to be really cool too. They play rock music and have laser shows in the theater.
Dr. Williams: Oh.
Dr. Hooven: That's on my list.
Dr. Williams: I have not experienced that either. Most certainly, we'll have to add that onto my bucket list. And though, while I could talk about the Science Center for a very long time, because I also love it, that is most certainly not why we're here. We are so excited that you are here to talk to us about your research.
Dr. Hooven: Great.
Dr. Williams: So, would you mind just starting to tell us a little bit about your story? How did you become interested in neonatal health?
Dr. Hooven: Like a lot of people, I found pediatrics when I was a medical student, and felt like those were really my people. I loved being around the kids and families. And when I went to the NICU for the first time, my mind was really blown by the awesome experience of being there for babies being born, and taking care of them right after, and then taking care of them during, often this very long journey that they have in the NICU. They can spend many months in the NICU if they're born really prematurely, or if they have serious problems. So, it's an amazing team effort, and you get to know those families at a time in their lives that for them is often the most stressful, the most significant, and you can really have a huge impact in that way. And it doesn't take long being in the neonatal ICU for a person to realize that infection is a huge problem in babies, and especially in preterm babies.
They're really susceptible to bacterial infections, which is what I study, that older kids and adults are much less susceptible to under normal circumstances. So I got interested in that basic question, really when I was a fellow doing my subspecialty training, is what is going on with these particular bacteria that infect babies and preterm babies and don't infect older kids. And there's one bacteria in particular, which is called Group B streptococcus or GBS, and that's what I study in my lab now, to try to understand how that bacteria causes the serious infections that we see and if there are potentially better ways to stop them.
Dr. Agnihotri: That's fantastic. In terms of your research, do you study the genomics or the genetics of the bacteria and does this lead to the discovery of new treatments or antibiotics?
Dr. Hooven: Yeah, exactly. Yeah. So, I occupy what I've come to recognize as an unusual niche in neonatology. I take care of babies in the hospital and I take care of bacteria in the lab.
Dr. Agnihotri: A niche within a niche.
Dr. Hooven: Yeah. But our philosophy to studying Group B strep infection is a “know thy enemy” approach. So, we look hard at the genes that bacteria has and try to understand how it changes its program when it's in the human body, and particularly when it's in a fetus or a newborn, to potentially become more dangerous in response to signals that it might be seeing during pregnancy or early life. So we reprogram GBS in different ways, we put it into lots of different models of disease, and try to figure out what particularly turns it on and makes it a bad actor in these circumstances, with always the hope of trying to figure out a better way to stop it. Because what we do right now is really a pretty blunt instrument.
Dr. Williams: So, as a hospitalist, I see babies that come in with fevers and then sometimes have GBS, so I'm used to treating these infants with pretty “big gun” antibiotics until we know exactly what it is. And it's even more specific for neonates because their immune system is even more susceptible to these than some of the older infants.
Dr. Hooven: Yeah.
Dr. Williams: So are you in your lab then looking at mostly the genes, how that'll affect treatment, or are you trying to find a way to, I don't know, change the genes so that it doesn't happen at all?
Dr. Hooven: Sure.
Dr. Williams: What are you looking at?
Dr. Hooven: Yeah. I think, and I think a lot of people who study these kinds of infections, feel like this is a type of infection that one could vaccinate against. What we do right now in the United States is we test pregnant women to see if they're colonized with this GBS during pregnancy. Basically, if they have GBS living on them, which usually doesn't cause disease in them, but if we find it there, we know that that's a risk for the baby, and so what we do is we wait until they're delivering, and then, just like you said, Alli, we blast them with big time antibiotics to really just clear the system and get that colonizing GBS out of the mix. But it's not a great strategy, that requires a lot of antibiotic administration, it's very complicated to do all this testing, to follow these moms, and then to make sure that the right moms get antibiotics, and the moms who don't have GBS don't get antibiotics.
So, we envision an easier way, which would be to vaccinate women before they're pregnant so that their effective antibodies against GBS could be passed to the fetus and would protect the baby during the newborn period. So really what we look for with my genetic reprogramming in the lab is targets on the outside of the bacterial cell that could be useful for a vaccine. Everybody I think in the world now knows about the spike protein, which is the coronavirus vaccine target.
Dr. Agnihotri: Yeah.
Dr. Hooven: So we'd like to find the equivalent surface protein, a surface target, that's shared among all GBS, and it's really important for causing these infections. The idea being that if you could gum it up with an effective vaccine, that you might be able to protect those babies.
Dr. Williams: Yeah. I'm just thinking about the outcomes of that, for many years from now, the outcomes of what this could mean for women and for babies, that would completely change the way in which we treat infants that have it at all, and even a huge impact on the numbers of babies that we see. That's amazing.
Dr. Hooven: Yeah. And it's a huge problem worldwide. We know from our work here what the situation is in the United States, which is far from perfect, but most countries can't do what we do in terms of screening everybody and giving everybody these antibiotics. So, in the developing world, where really the only option is just to watch and see if a baby gets GBS disease, or if a pregnant mom gets GBS, which can really endanger the pregnancy, there's just no good strategy in those places. And so, again, vaccines are hard, and we've sort of learned that over the last couple of years, but I continue to believe that there's a path to really change, like you're saying, how this bacteria affects vulnerable babies.
Dr. Agnihotri: Right. Your research is so cool. So, in terms of, you were mentioning vaccines, the long-term goal, are there new technologies that you kind of like to play with in the lab or other types of targeting strategies?
Dr. Hooven: Sure. Yeah. So, when we study bacterial genetics, a really old way of doing this that's tried and true is you make a mutation, you break a gene, so that it's not working, and then you see what effect that has. And that's great, but you have to know which gene to break beforehand, and it takes a lot of time. It's hard to go in there and reprogram that DNA in that way. We've recently been using CRISPR-Cas, which I'm sure a lot of people listening have heard of, which is a way to really program genetic changes very quickly in a lot of different cells.
CRISPR-Cas was originally discovered in streptococcus very similar to GBS. And we use it to break everything, in a systematic way, in a way that we can keep track of. We turn off, really all of the genes that we think might be involved in these infections, one at a time, and then we can take those broken, turned off GBS mutants and put them into experiments, models of disease, and see which ones are really important. And that's just a much, much faster way... It just presses fast-forward on a process that otherwise takes months or years to make a handful of mutants, we can make these now in days or weeks in the lab and have them-
Dr. Williams: Wow.
Dr. Williams: That sounds a little intimidating, right? You can break and make a new bacteria almost.
Dr. Hooven: Yes. Well, hopefully one that is deficient.
Dr. Hooven: I'm fundamentally impatient, and I think in my research that's driven a lot of the things that I've tried to do. When I first started making mutants in GBS, I thought, I can't do this thing that takes three months from start to finish, I'm just not that patient a person. So I've always been looking for ways to speed it up and try to find something faster.
Dr. Agnihotri: That sounds amazing. Can you comment on one of your favorite discoveries or something you're just so passionate about in a lab, that just gets you going?
Dr. Agnihotri: And your team.
Dr. Hooven: Yeah. Well, we've been working for the last couple of years on an exciting discovery we made, that was a GBS system that nobody had described before, that seems to really allow it to survive, allow the bacteria to survive, in amniotic fluid. A baby in the womb is surrounded by amniotic fluid, and that's pretty protective actually. Most bacteria won't grow there and won't cause infections. So we asked the question, what is it in GBS that lets it survive in there? Lets it get in there, and divide, and get into the baby, before the baby's born, which is really a risky situation. And we found this signaling pathway in GBS that seems to get turned on when it gets into amniotic fluid, and it's really different from what other bacteria have, and we think it may be a real keystone in how these early infections get set up. So, we're working hard on trying to understand exactly how that works, is it something that we could target with a vaccine? Like I was telling you before. So that's a big project that's going on with us.
Dr. Agnihotri: That sounds exciting.
Dr. Williams: I feel like right now too, with all of the COVID stuff that's been going on, and vaccine development, it makes, at least for the layperson who doesn't do research, like me, feel like vaccines can just be created out of nowhere, which is not true at all.
Dr. Williams: So, what is your short-term research goal and then your long-term research goal? What does your timeline look like for all of these amazing, hopefully, developments that you can achieve?
Dr. Hooven: Yeah. Well, you're really right that the process of developing a vaccine is and should be very carefully regulated, and that everything that gets sent out to the public has been really tested extensively. We're very much in the discovery phase right now, of trying to understand what this specific bacteria does that's different. This is a very niche area of research. It affects people in a very real way, but it's a little different from some other things that we vaccinate for, in that it really is just this very specific population.
So, to answer your question, I think we need to understand more, and to use the spike protein analogy with coronavirus, again, when that vaccine was made, a lot of work had gone in long before, to really understand exactly how that spike protein works, what it looks like, and how to gum it up with antibodies from a vaccine. And that's sort of the phase we're at right now with GBS. So I would like in my next 10 years to make fundamental discoveries about surface proteins on this dangerous bacteria. And then, I think once that's under our belt, then it's time to really start thinking about how to put together something that could be used in research trials, carefully done research trials with patients, to see what sort of responses they get.
Dr. Agnihotri: Right. And in terms of research trials, your research, the dark side of research is always funding, and less than 10% of NIH funding goes towards pediatric research. Can you comment on how the field is, and is funding always an issue? And typically, a lot of this research is quite expensive, but very necessary as you alluded to.
Dr. Hooven: Yeah. What you're saying is a hard, but definitely true aspect of doing this kind of research. The funding is very competitive. It has to also get renewed, it's not as though someone gives you a green light and says, here you go, do good work for the rest of your career and let us know how it goes. It's much more sort of, what have you done for us lately? And that part is hard. I enjoy writing, I like to organize my thoughts and try to make them make sense to anyone reading them. So, in that sense, all the grants that I have to write to do this work, which is a big part of my job, can be pleasurable. I try to look at it as an elaborate writing project. I wish there were more funding, I hope that more funding will be made available in the future, but we do the most with what we have right now.
Dr. Agnihotri: No, that's fantastic. Allie and I just found out that we have medical students and residents and fellows that tune into this. Any advice for people that want to follow in your footsteps, or excited about this type of research or clinical practice?
Dr. Hooven: Sure. Well, hi to any trainees who are out there listening to this. It's a wonderful path to do science and medicine together, I've always found them really complimentary. Both of them are so challenging and a lot of fun, and you get to work with people that are second to none, in both areas. It's sort of a cliche, but it's just true, that your mentors and the people who help you get there are the most important people in your lives. So, if you're interested in doing this kind of work, I would say start with a person who you find really compelling, and to be an excellent leader, and who can teach you, start with that person as your mentor, and worry less about what the actual science, the fine-grained details of the science are. That's certainly important, but there's a lot of overlap and there's a lot of fluidity in science, especially early in your career. So, you can learn a huge amount from a great mentor and then make a change to a different area later on and take those lessons with you.
Dr. Williams: This is such exciting research, and I think that that's really, I appreciate you sharing that because there are many physicians that do clinical work, there are many scientists that do bench work and lab work, and though there are some that do both, I find those fewer and further between. So it's great that we have someone here that can speak to both sides, of both the clinical and the bench research. It's amazing.
Dr. Hooven: Thank you. It is. It's a lot of fun.
Dr. Agnihotri: So, as a thought leader, you're being very humble... We were alluding to the ultimate goal in 10 years, what are the burning questions in the field that you'd like to answer yourself, but also your colleagues, and is it just streptococcus or are there new strains emerging? Is it-
Dr. Hooven: Yeah. No, it's a great question. I think something that we've learned in the last, oh, 10 to 15 years, that's really changed the way we think about babies and bacteria, is the emerging field of the microbiome. These are all of the bacteria that live on us and in us, and they're really an important part of health. We think of bacteria often as something that causes disease, but we've learned that we harbor enormous numbers of bacteria that help us remain healthy, and those bacteria meet babies, and babies meet those bacteria, during the first hours of their life.
It's a fascinating, and I think still not very well understood process of how you take a brand new human, who really has never seen a bacteria in development before, and suddenly introduce them to a vast world of billions and trillions of bacteria, and how that process gets set up in a way that sets them forward in health or potentially in disease, and how those bacteria talk to each other and maybe provide an avenue for bad actors like Group B strep to cause infection. Those are huge, fascinating questions that I think the people in my world who study bacterial infections and babies are thinking about a lot.
Dr. Williams: This is amazing. I was listening so actively that I didn't even look at the time. I think we're running pretty close to the end of our time for our episode here. Any last minute words of advice for folks out there, which you've already given a lot of, or hopes and dreams for your future research to talk about?
Dr. Hooven: Well, I would maybe close with saying thanks to the patients and their families that I take care of. At the end of the day, it's that same experience that I was talking about at the beginning, being there with people early in their lives, and during this critical time when babies are in the NICU, that gets me up in the morning. And I'm grateful to them for trusting me with their care and for the opportunity to think about these research questions that I so enjoy.
Dr. Agnihotri: It's amazing. Is there any social media, Twitter, website, that you could recommend, that someone can follow you on? Or that'll be on the children's website?
Dr. Hooven: I do. Well, there's a website for my lab, which is hoovenlab.com.
Dr. Agnihotri: Perfect.
Dr. Hooven: And people can keep track of us there.
Dr. Agnihotri: Excellent.
Dr. Williams: That sounds awesome. Thank you so much again for taking time out of your day to come talk to us and explain to us your important research. And we are also thankful to all of our listeners for tuning in today to this episode of That's Pediatrics.
Dr. Hooven: Thanks so much.
Dr. Agnihotri: Thank you.
Voiceover: For more information about this podcast or our guests, please visit chp.edu/thatspediatrics. If you've enjoyed this episode, please be sure to rate, review, and subscribe, to keep up with our new content. You can also email us at podcast.upmcgmail.com with any feedback or ideas for topics you'd like our experts to cover on future episodes. Thank you again for listening to That's Pediatrics. Tune in next time.
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