#030 - Hydrogen, Metformin, and the First Two Hours - Rethinking HIE Neuroprotection with Brian Kalish
Hello friends 👋
In this episode, Misty and Betsy sit down with Dr. Brian Kalish, a neonatologist-neuroscientist at Boston Children's Hospital, for a wide-ranging conversation on building a career at the intersection of fetal and neonatal brain injury research. Brian traces his path from public health and pediatric surgery to neuroscience, describes what "technical courage" means in the lab, and shares the story behind his move to SickKids Toronto and back. He discusses his lab's work on Down syndrome neurobiology, a newly funded multi-center trial targeting transposable element activation, and an ambitious hydrogen gas trial for hypoxic-ischemic encephalopathy using an Exception from Informed Consent framework. A conversation about mentorship, global health, and staying inspired through the hard parts of physician-scientist training.
Link to episode on youtube: https://youtu.be/lwxTHN5pH30
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Featured Manuscripts From Dr. Brian Kalish
Spatial transcriptomics of the developing mouse brain immune landscape reveals effects of maternal immune activation and microbiome depletion.
Kukreja B, Jeon S, Cao W, Rusu B, Harrison CF, Ghazisaeidi S, Tahmasian N, Feng MY, Chan R, Loan A, Johnston WB, Padhy S, Rakoff-Nahoum S, Wang J, Yim YS, Kalish BT.Nat Neurosci. 2026 Mar;29(3):732-745. doi: 10.1038/s41593-025-02162-3. Epub 2026 Jan 6.PMID: 41495254
Feng MY, Cao W, Tahmasian N, Kukreja B, Li G, Rusu B, Youn JY, Kalish BT.Nat Commun. 2025 Sep 30;16(1):8689. doi: 10.1038/s41467-025-63752-0.PMID: 41027953 Free PMC article.
Lewis JD, Miran AA, Stoopler M, Branson HM, Danguecan A, Raghu K, Ly LG, Cizmeci MN, Kalish BT.J Pediatr. 2026 Jun;293:115033. doi: 10.1016/j.jpeds.2026.115033. Epub 2026 Feb 13.PMID: 41692231 Free article.
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The transcript of today's episode can be found below 👇
Misty Good (00:01.67) Hi and welcome back to At the Bench, the Neonatal Physician Scientist Podcast segment of the Incubator. I'm Misty Good, a neonatologist-scientist and the Division Chief of Neonatology at the University of North Carolina at Chapel Hill, and I'm co-hosting today with Dr. Betsy Crouch. Betsy, would you like to introduce yourself?
Betsy Crouch (00:21.2) Hi everyone, I'm Betsy Crouch. I'm a neonatologist, a vascular biologist, and a neuroscientist at the University of California, San Francisco, and I'm a new associate professor. Thank you — it feels hard won. My lab was actually giving me a hard time about celebrating it recently, and I told them, which is true, that I'm more excited now by our weekly data update meetings than I've ever been. It feels like the science is reaching a next level as my position advances, and that's really exciting.
So I'm grateful to be co-hosting with Misty today, and grateful for our guest, Dr. Brian Kalish. Brian and I got to know each other because we're both part of the Pediatric Scientist Development Program (PSDP), now run by Dr. Sally Permar — we're actually hoping to have her on the podcast soon to talk about her leadership of that program. The PSDP was a huge catalyst in my career and in Brian's, and we've since collaborated on a couple of studies that continue to be really fun. So we're very happy to have you today, Brian — could you introduce yourself?
Brian Kalish (01:54.767) Of course, thanks for having me. By way of introduction, I'm a neonatologist and neuroscientist at Boston Children's Hospital. I'm an associate professor of pediatrics at Harvard Medical School, I hold the Merton Bernfield Chair in Neonatology, and I'm the director of our Program in Neonatal Neuroprotection and Neuroplasticity.
Misty Good (02:17.679) That's fantastic. We're going to hear all about your journey. Brian, take us back to the beginning — tell us how you became interested in neonatology, and then in your scientific path. Feel free to talk about training, mentoring, anything you like.
Brian Kalish (02:37.678) Sure. I have a bit of a non-conventional path toward being a physician-scientist. I grew up outside of Chicago, and I'm the first in my family to go to college and medical school. I went to Johns Hopkins for undergrad and studied public health, and I was bitten by the research bug early on — though I did very different research then than I do now, studying global health and infectious disease.
I went straight through from undergrad to medical school at Harvard. At the time, I thought I was going to be a pediatric surgeon, and I worked hard down that path, joining the lab of Dr. Mark Puder, a really extraordinary surgeon-scientist here at Boston Children's Hospital. I was in his lab throughout medical school and did an extra year there funded through the Howard Hughes Medical Institute, mostly studying small lipid molecules that regulate angiogenesis, as well as mechanisms of organ regeneration.
But I fell in love with being a scientist and with the idea of running my own lab. So very late in medical school, at the eleventh hour, I made the switch from surgery to pediatrics — something I'd always said I would never do, and it shocked everyone. Really, it came from wanting to run a research lab and feeling like a balance between being a pediatric intensivist, in some form, and being a scientist was a good fit for me.
I did residency through the Boston Combined Residency Program in Pediatrics, between Boston Children's Hospital and Boston Medical Center, on the accelerated research pathway — two years of pediatrics, then four years of neonatology fellowship. During that time I did my postdoctoral research fellowship in the lab of Michael Greenberg, who was then chair of neurobiology at Harvard Medical School. That's also when I participated in the Pediatric Scientist Development Program with Betsy and others, which was really formative for my path and solidified my desire to be a serious pediatric scientist. I also met extraordinary people from across the country and the world — scientists and leaders — which was very inspiring.
I spent about four and a half years in Mike's lab as a postdoc, including my transition into my first faculty position at Boston Children's and becoming an instructor at Harvard Medical School. Around that time I received my K08 (NIH Mentored Clinical Scientist Research Career Development Award). I was on faculty at Boston Children's for about two years, and then I was recruited to the Hospital for Sick Children and the SickKids Research Institute in Toronto. That transition is something we can talk more about — I was really looking to leave the Boston area and the Harvard bubble, and venture somewhere new for my own intellectual and clinical development. It was an extraordinary journey, but also challenging, since we crossed a closed border and moved my lab and my family during the COVID-19 (coronavirus disease 2019) pandemic.
Nonetheless, I started my independent research program there at SickKids and was there for about four and a half years before being recruited back to Boston Children's Hospital. I've been back for a little over two years now. My lab broadly focuses on developmental neuroscience, trying to understand the neurobiology of fetal and neonatal brain injury. Our work spans from fundamental molecular neuroscience — including regulation of mRNA (messenger RNA) translation in the brain — to more applied work on the role of the maternal environment in shaping fetal neurodevelopment, to large animal models of fetal and neonatal brain injury, including sheep and rabbit models. We also have a few early-phase clinical trials of novel interventions to protect the newborn brain — so really spanning the spectrum.
Betsy Crouch (07:02.098) I love this gig, because even with people I know well, I learn new things.
Misty Good (07:09.834) There's so much to unpack from just those first few minutes — it could take us in so many different directions.
Betsy Crouch (07:18.66) Where should we start, Misty? I wanted to know more about global health, and how that shaped things. I think many of us were fortunate to get opportunities to think about international health delivery — and even as a neonatologist running a wet lab, thinking about the global impact of neonatology is definitely on my consciousness. Does your public health background play a role in how you craft your research program now?
Brian Kalish (08:00.109) Yeah, that was a unique part of my path — I lived for about seven months in Zambia, both in the capital and in a rural area, and it really shaped my trajectory as a physician. My wife also has a global health background, and I've promised her that at some point we'll get back to that aspect of our lives. More recently, because of my interest in hypoxic-ischemic encephalopathy (HIE), which carries a high burden in low- and middle-income countries, I've thought a lot about how new therapeutic approaches that might be viable in the United States would be far less viable in those settings, and what unique strategies we might need there. So it's on my mind quite a bit.
Betsy Crouch (08:50.588) To say it explicitly — the Gates Foundation is very interested in the recent clinical trials showing that therapeutic hypothermia isn't protective in low- and middle-income countries, so a different approach is needed. I've found that inspiring too. Do you have anything you want to share on that yet, or not yet?
Brian Kalish (09:16.588) Not yet. I've spoken a little with folks from the Gates Foundation and others about this. I think the HELIX trial was one study with a particular result, but I think there's potential in translating some of our practices into a bundle of neuroprotective interventions — even simple, low-cost interventions — depending on the setting. It's something I'm very interested in, but I don't have a lot of traction yet.
Betsy Crouch (09:48.338) We'll look forward to talking with you about that in the future. Maybe that gets into a bit of your NICU (Neonatal Intensive Care Unit) director role now.
Brian Kalish (09:55.842) Sorry, say that again, Betsy?
Betsy Crouch (09:57.093) I called you a "Nikken" director — that's the term we use at UCSF, the neuro intensive care nursery. What do you call it at Boston Children's?
Brian Kalish (10:05.11) We've chosen explicitly not to say we have a "neurocritical care program," quote-unquote — because, and I might be controversial here, when you look at the websites of most neonatal neurocritical care programs, we're often just saying we do things like brain MRI (magnetic resonance imaging) and EEG (electroencephalogram) and consult neurology, all of which are pretty standard of care across NICUs in the United States. I think that lacks actual innovation, so after much discussion we made the intentional decision not to call it a neurocritical care program in that way. We obviously collaborate very closely with our neonatal neurologists and do all of those things, but our Program in Neonatal Neuroprotection and Neuroplasticity is more focused on bridging preclinical studies to early-phase and even first-in-human trials of novel interventions — really trying to bring actual innovation to infants at risk for brain injury.
Betsy Crouch (11:08.37) Thank you for clarifying. I'll let Misty jump in — I could keep going, but I'll let a non-neuroscientist go for it.
Misty Good (11:18.492) Actually, I did want to talk about neuroscience, because I think it's really interesting how people choose their scientific niche. For me, I'm obviously passionate about necrotizing enterocolitis (NEC) — but when was the moment for you when you decided the newborn brain was the problem you wanted to dedicate your career to? And I was reading in preparation for this episode, and you used the phrase "technical courage" when talking about Mike Greenberg's lab. We have a lot of trainees who listen — and I just finished interviewing fellows for this recruitment season — so I think our listeners would be grateful to hear what technical courage means to you, and what it means for a fellow embarking on choosing their mentor and their research direction.
Brian Kalish (12:42.264) Of course. First, in terms of how I came to neuroscience — I came to it a bit late. As mentioned, I was involved in a lot of research at every stage of my career, but did a lot of infectious disease research and epidemiology, then lipid biology and mouse models with Mark Puder during medical school. But as I was entering residency, I took a step back and did a self-reflection exercise, thinking deeply about where I wanted to focus my scientific efforts, while also thinking about where I wanted to do a postdoctoral fellowship.
I reflected on what the biggest unsolved challenges in neonatology were. We've made enormous progress over the last several decades in the survival of the sickest and smallest babies, but I'd argue that the neurodevelopmental potential and neurologic outcomes of the sickest children remain an unsolved challenge. Especially as survival of the sickest continues to increase, we have to rethink what their long-term neurodevelopmental outcomes will be. So opportunities to better protect and promote resilience of the newborn brain became of paramount interest to me, and that's why I decided to do a postdoc in neuroscience.
At the time, one of my mentors at Boston Children's, Sam Lux, who was then vice chair of research, sat down with me and went through a list of various neuroscientists in Boston. I went on what was essentially a speed-dating exercise, meeting about 20 potential mentors to find who I might click with — not just with the science, but with them as a person. Mike Greenberg was one of the last people I met with. Sam Lux — I don't think he'd mind me saying this — warned me that Mike could be a bit of a curmudgeon.
I had this amazing, hour-long first meeting with Mike Greenberg, and at the end of it I said, "Sam told me you could be a bit of a curmudgeon, but I can't believe it, having met you." To this day, Mike likes to joke about me calling him a curmudgeon the first time we met. Nonetheless, he took me into the lab as a postdoc, and that was transformative — I was the only physician in the lab at the time, and the methodologic rigor immediately impressed upon me by Mike, and by my fellow postdocs and graduate students, brought my research to a different level.
I sincerely appreciated Mike as a mentor because he gave a great deal of independence, which was also challenging in those early years — I didn't have a lot of specific guidance and did a lot of learning to acquire skills. But ultimately that proved to be a real advantage, because it helped prepare me to be an independent scientist. I think my time in Mike's lab really epitomized that concept of "technical courage" — a term I borrowed from Michael Brown, the Nobel Prize–winning scientist at UT Southwestern. In his presidential address to the American Society for Clinical Investigation, he coined that term to describe the ability to leverage and invent any new method necessary to solve a particular problem you're interested in — to avoid the temptation, as a physician-scientist, to gain expertise in one method and just turn that crank over and over, and instead let your science be driven by a particular problem or question, leveraging whatever methods are necessary to answer it. Not being afraid of complex or new methods.
Misty Good (16:58.908) That's terrific — a really great way to think about it.
Betsy Crouch (17:05.788) There are so many good nuggets in that story, Brian, that I want to emphasize for our listeners — physician-scientists at all stages of training, including new associate professors like us who are still, in some ways, in training ourselves. When you talk about the process of speed-dating to find a postdoc mentor — I did a very similar process here at UCSF. It was actually such an exciting time, because I had a track record of productivity in research, so I could send people my previous papers and say, "I know how to put one and two together, but I'm interested in this problem of germinal matrix hemorrhage."
I went around to different scientists at UCSF who had very different perspectives on how to approach that problem. I talked to mouse-model people, I talked to zebrafish people who were doing cardiac regeneration — you know, if you cut off a piece of the zebrafish heart, it fixes itself, but if you're a postnatal mouse, it doesn't regenerate the way an embryonic mouse heart would. I thought that was a different angle I could use.
I also spoke to an engineer, Wendell Lim, at UCSF, who's very successful in designing synthetic Notch circuits for immune cell activation or inhibition, targeting cellular therapies to different areas. When I told him about germinal matrix hemorrhage, he said, "Why don't you just design the vascular tree the way that it would be protective?" I still think about that framing and how helpful it was.
I just want to emphasize — many of us wouldn't necessarily assume that other scientists would be interested in talking to a pediatrician or a neonatologist, but in fact, I think we bring a useful perspective to scientific techniques. So I want to encourage everyone: informational interviews are hugely helpful, both for you and potentially for the lab you might join. Do ten of them — that's what I did too.
Brian Kalish (19:34.009) It's funny — it sounds like you approached some of those meetings with more preparation than I did. You had this idea in mind about germinal matrix hemorrhage going in. That makes me reflect that I probably walked into these meetings with much less scientific sophistication. I had a passion for developmental neuroscience, but I met with folks from a diverse array of backgrounds — stem cell biologists, geneticists, others — without having formed a very thoughtful scientific interest, probably until I was deeper into my postdoc. I was grateful for that environment, which let me meander a bit. I actually spent the first year of my postdoc learning coding, which was a skill I'd wanted to acquire.
Betsy Crouch (20:29.158) There's breadth and there's depth. You probably had a bigger breadth of scientific exposure that you're now employing quite nicely. I'm kind of a one-trick pony — I really like central nervous system (CNS) blood vessels. I've been working on them since I was a PhD student in 2008, and so far, so good — we still haven't solved it. So I'll continue.
Misty Good (21:00.026) I think you've got to do what drives you — what makes you get out of bed in the morning, what makes you want to read a paper outside your field, or tangential to it. Or what bugs you at the bedside that you can take back to the lab, to move the field forward.
Brian Kalish (21:26.112) What you just said, Misty, really resonates with me. I remember being a resident, part of conversations with families of children with HIE, or families of premature children with significant brain injury, asking, "Okay, so what do we do? What's the therapy we're going to give to address this brain injury we've diagnosed and described so eloquently?" And inevitably, the neonatologists and neurologists were basically offering prognostication without anything therapeutic. That struck me very profoundly, and I was inspired to try to fill that gap.
Misty Good (22:11.034) I love that — it's all about inspiration, where you find it, and how you build from there.
Betsy Crouch (22:20.282) There are so many cool things to talk about. Biographically, could you elaborate on how you thought about starting your own lab — the conversations that led to starting it at SickKids? Any advice or tips for others on the cusp of that decision, maybe considering international options? We work fairly hard on At the Bench to talk with physician-scientists across the world in different places, because diverse perspectives on our problems are so important.
Brian Kalish (23:02.558) At that time, about two years into my first faculty position at Boston Children's, I was reflecting that I'd been in Boston a long time, in this very insular training environment within the Harvard neonatology institutions. My wife and I had always expressed interest in potentially working outside the United States, for a bit of an adventure. I happened to meet Ronnie Cohn, CEO of SickKids, at a conference — he gave a presentation at a Pediatric Scientist Development Program conference, and I approached him afterward because I found the talk inspiring, and thought it was unique that such a rigorous basic scientist was leading the institution. That conversation sparked the idea of considering a job at SickKids.
It felt like a pull in the sense that there were opportunities for leadership and growth that may not have been possible at Boston Children's at that point in my career, given the culture here at the time. It also felt like an opportunity to sharpen my clinical skills and broaden my research horizons in ways that wouldn't have been possible had I stayed. So, in the spirit of adventure, we were pretty enthusiastic to take that opportunity.
Betsy Crouch (24:35.206) Does your license work in Canada? Can you talk a bit about that piece?
Brian Kalish (24:38.51) I had an academic license — I couldn't practice in a community setting, but I had a license sponsored by SickKids.
Betsy Crouch (24:49.616) Not in a private practice setting. Okay.
Misty Good (24:55.056) I have a semantic follow-up. Piecing together the timeline — you were on a K award, right? Can you talk about, one, moving your K award, and two — because I had to move mid-K myself, and it's an experience — moving it internationally? Were you able to, or did you have to relinquish it?
Brian Kalish (25:19.842) I relinquished the K at that time. I think it was a matter of weighing the money and resources — part of the startup package at SickKids factored into that decision — but ultimately I relinquished it because it's not possible to move it internationally. I felt that the opportunity to start my own lab outweighed that. A lot of what the K provides is salary support and mentorship, and the structure in Canada is different — particularly at SickKids, which is very supportive of physician-scientists. My salary was covered by the institution, and I had guaranteed protected time, which gave me the focus to start my lab.
Misty Good (26:09.02) That's terrific. Follow-up — so you're moving, starting your lab — tell us what you decided to start working on then, and how your science has evolved since.
Brian Kalish (26:23.874) Another important aspect of that move for me was wanting to be embedded in a hardcore science department, not just within pediatrics. Part of the recruitment was joining the Department of Molecular Genetics at the University of Toronto, an outstanding department with extraordinary scientists and colleagues — I wanted the opportunity to mentor graduate students and have those colleagues. That was another driving factor.
In terms of what I started working on — I think I made some mistakes along the way, which we can talk about, and probably approached it a little naively. But one of my strong interests in the move was being able to study human brain tissue. Betsy and I have talked a lot about the barriers I faced doing that in Boston, so I wanted to seize this new opportunity to study primary human brain tissue as much as possible. A lot of the work we did was either primary human brain tissue or human cell-line-derived neural cells. It took a while to set up the process for acquiring that tissue, but that was a big focus of our early efforts.
As part of that, I've had a longstanding, somewhat side interest in the neurobiology of Down syndrome, partly inspired by a family member of mine who had Down syndrome. I'd always said that when I had my own lab, I'd devote part of it to studying Down syndrome, and that melded well with the human brain tissue focus. So we launched efforts to acquire primary human brain tissue from individuals with trisomy 21 and from neurotypical individuals, trying to decode some of that neurobiology. That was some of our early work.
Misty Good (28:24.454) That's terrific, I love that.
Betsy Crouch (28:24.838) Yeah. Thank you for sharing that, Brian. I was curious if you could tell us a bit more, jumping off from your recent publication on trisomy 21, about what you're excited about in that space.
Brian Kalish (28:40.206) Sure. We were fortunate to publish a paper last fall in Nature Communications on this work using human brain tissue to study Down syndrome. One of the key discoveries was that we identified a lineage-restricted derepression of transposable elements in neuroprogenitor cells in the Down syndrome human brain.
That was of particular interest because work by Rusty Gage and others had previously shown that these transposable elements — particularly LINE-1 (Long Interspersed Nuclear Element-1) — are critical for modulating neuroprogenitor cell state. I also found it fascinating because there's emerging data showing that derepression of transposable elements is a final common pathway in aging and neurodegeneration, which is particularly relevant for Down syndrome — a progeroid-type condition with accelerated aging, where by age 40 there's near-ubiquitous Alzheimer's disease in individuals with Down syndrome. So there's an interesting association there.
Now we're fortunate to have an R01 (NIH Research Project Grant) to study the mechanisms of LINE-1 derepression in Down syndrome neuroprogenitor cells and look at potential pathways to target it. And the great news is that just a few weeks ago we were funded with a $10.5 million UG3 (NIH cooperative agreement mechanism) to conduct a multi-center clinical trial inhibiting transposable element activation in individuals with Down syndrome — a collaboration with Brigham and Women's Hospital, Mass General, and several other sites across the US, aiming to therapeutically target that aberrant transposable element activation.
Misty Good (30:34.714) That's amazing, congratulations — what an incredible, exciting announcement. Especially with those kinds of resources, it should be transformational for that space.
Brian Kalish (30:41.784) Thank you. Especially now, and I think for the Down syndrome community, it hopefully will be something really important and significant.
Misty Good (30:59.404) Terrific. Can you talk about that continuum — you have a lab, but you also mentioned this clinical trial. Where do you fall, and what are you doing across that spectrum? One of the fellows I interviewed earlier today mentioned they've done a lot of basic science but feel pulled more toward the clinical side — can you speak to that pull for you?
Brian Kalish (31:26.422) I'd fundamentally consider myself a lab scientist, and I don't think I'd ever want to give up the fundamental neurobiology we do in the lab — that's really important to me. We could nerd out about all the basic work we're doing, but I've also tried to grow the more translational aspect of my work, particularly in this transition back from SickKids to Boston Children's. That was a key motivation — having the resources to grow that side. I'm fortunate here to be supported by a clinical research program that provides extra resources, like a study nurse and other support, to help grow that translational aspect. Right now I'm trying to balance both — ask me again in five years and I'll let you know how that dance is going, but that's how it's currently evening out.
Betsy Crouch (32:26.16) I also want to offer my congratulations — it's so rewarding when you move from seeing something under the microscope to thinking about that patient, and in your case, the family member who may have been impacted by your work. To take it a step further — are you the one having the meetings with the FDA (Food and Drug Administration)? Have you had to learn the whole new nomenclature of the IND (Investigational New Drug application) and all these regulatory steps? I'm fortunate to work closely with Tippi Mackenzie, who's been on the show — she thinks of herself as a fetal therapeutics person addressing genetic diseases in the womb, and she's now quite experienced with all these interactions. It's been helpful to learn from her, but also really humbling.
Brian Kalish (33:23.138) Very humbling, and particularly overwhelming with the bureaucracy — not my favorite way to spend part of my day, to be honest, but I think it's super important. I'm lucky enough to have two Investigational New Drug designations from the FDA for two clinical trials we're leading. We have two studies in HIE — one is repurposing the drug metformin to promote neuroplasticity. We have an IND for that, and we've enrolled close to half of the patients for that study. We also recently received NIH funding for a clinical trial of inhaled hydrogen as a novel neuroprotectant in children with HIE, and we'll be launching a multi-center trial for that. That path through the FDA was long and challenging — the trial will actually leverage an Exception from Informed Consent framework, so we can enroll children within two hours of birth and randomize them to hydrogen. So you can imagine the complexity of those FDA interactions.
Misty Good (34:33.87) I can't even imagine it.
Brian Kalish (34:40.428) But I think it will be amazing for our field. What I think has been missing is that we can't save neurons that are already dead, from my perspective — giving interventions hours later, once the neurons have died, doesn't help. If we actually want to move the needle, we need to intervene while there are still neurons to save.
Betsy Crouch (35:01.854) To invoke Donna Ferriero's framework — the therapeutic landscape of hypoxic-ischemic encephalopathy: there's the initial insult, the neuronal damage, then the inflammatory piece, which therapeutic hypothermia targets, and then the regenerative capacity, for which we don't have any FDA-approved therapies. So I think it's great that you're going after the initial insult — because you're right, if we can't move the needle there, the rest is going to be much less impactful.
Brian Kalish (35:40.118) Yeah.
Misty Good (35:40.995) One of those barriers is consenting — they have to be cooled within six hours, obviously earlier is better, but when you work in a large referral center, oftentimes the families aren't there, or the mother's at a general hospital, or something like that. So it does make consenting a barrier. I'm glad you were able to move the needle on that — I think that's tremendous.
Brian Kalish (36:08.258) We're doing it in a very family-centered way — there are specific regulations around that. I'm lucky to engage closely with the Hope for HIE Foundation on this, and as part of the Exception from Informed Consent structure, we do extensive community and family engagement — that's a big part of the trial throughout. It's a balance of potential for benefit, low risk, and the fact that there's a critical window to intervene, because the hydrogen acts as a sink for the oxidative free radicals that form in a burst when we restore circulation after birth — but that's only targetable within the first few hours, at most, after birth.
Betsy Crouch (36:56.528) Brian, sorry — which publication did you work on that led to this idea, the preclinical data?
Brian Kalish (37:06.104) A lot of the work is still ongoing — unpublished data. But I'm lucky to collaborate closely with a cardiac intensivist here who's been studying hydrogen for post-cardiac-arrest care in older children, and we're now bringing that into younger children and infants, and thinking about preterm infants in the future from an antioxidant standpoint. One of the fellows in my lab is currently working on experiments giving hydrogen to mothers to protect the fetal brain in the setting of category 2 or 3 fetal heart rate tracings, using an ovine (sheep) model. That work is still ongoing.
Misty Good (37:55.771) That's really incredible. You mentioned your fellow's work — now that you're back, reestablished your lab, and taking on mentees, what advice would you give them when they're thinking about their project — how to choose a mentor who fosters physician-scientists, and what makes a project set them up for success?
Brian Kalish (38:31.98) Personally, I try to meet each mentee where they're at in terms of career goals — not everyone wants to be an independent lab-based scientist; some want a more translational career, or to collaborate closely with bench scientists while doing clinical work. I try to really understand their motivations and long-term goals, so we can design a project that meets those goals. For me, I think back to my mentor — what he offered was a wide berth and independence, but also, we just clicked so much on an interpersonal level, and that made my experience inspiring and easy. So I definitely encourage people to find a mentor they don't just like the science of, but feel they click with as a person — someone they can have as a career mentor for years to come, even after that particular research experience is over.
Misty Good (39:35.376) That's wonderful advice.
Betsy Crouch (39:39.421) We'd like to close with something fun about you and your research team. Favorite music to listen to while writing an IND? Or something your team does together? I have a type of music I use for running — something with a beat that gets the words out of me. Is there something your team does together, or any cool traditions?
Brian Kalish (40:08.822) This is the hardest question of them all — I should have prepared for this one, that's not fair, this wasn't provided in advance.
Misty Good (40:20.474) We just want to capture the cool personality of physician-scientists — any pearls.
Brian Kalish (40:24.886) It's generous of you.
Betsy Crouch (40:26.736) People have used this opportunity in sweet ways — Emin Maltepe just gave a shout-out to his wife and daughter. He said when he's not in the NICU, or in the lab, or in the LAM ICU where they work on preclinical therapies, he just hangs out with his wife and daughter — that's still the sweetest thing to me.
Brian Kalish (40:52.078) Well, I'll tell you the music I like to listen to while grant writing or IND writing is The Who — old school. And I'll tell you a funny anecdote — my daughter, who's about seven and a half, likes to come home late from the NICU or the lab with me, and she likes to name the babies — or the sheep, or the preterm rabbits. She's named many of the sheep in the lab. And of course, oftentimes the sheep have a finite lifespan in the lab, with defined study endpoints — but every night she says a prayer for the many sheep who've given their lives for science, which I think is adorable. Sparkle and Moonlight, and all the other sheep that have been named. So shout-out to Sparkle and Moonlight.
Misty Good (41:42.116) I love that, that's really sweet.
Betsy Crouch (41:45.542) That's delightful — somebody's really thinking about the sheep. That's good, since you have a lot to think about.
Misty Good (41:57.233) One last piece of advice for early-stage investigators out there, something inspiring to end on?
Brian Kalish (42:07.362) I think, obviously, in the current environment there can be a lot of pessimism — limited funding, a long training path, difficulty getting institutional support. There can be a lot of barriers. But the cadre of pediatric physician-scientists is small, and arguably shrinking, so finding people who inspire and support you is really important for maintaining momentum and positivity. Whenever I'm struggling with a rejected grant or a rejected paper, I reflect on the reasons I entered this path, and often need to talk that through with my wife or others, about what inspired me to do this at the beginning. That helps reset and recenter me in the face of struggles.
Misty Good (43:05.372) That's wonderful, thank you for that — great inspiration for all of us to remember.
Betsy Crouch (43:14.492) My pleasure. Brian, thank you so much for talking to us about a breadth of exciting therapies that I think will hopefully benefit many of our patients in the near future, and thank you for your dedication — I know that you're dedicated, sending emails at eleven PM! So sincerely, on behalf of our patients and our field, thank you — we look forward to hearing about all of your success. And thanks to our listeners for joining us — talk to you soon.
Brian Kalish (43:46.264) Thanks for having me.
Misty Good (43:47.281) Thank you so much for being here, take care.
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