Maya Hoptman

Interview with Courtney D. Fitzhugh, MD, National Heart, Lung, and Blood Institute, NIH (elected 2024)
Interviewed by Vijay Sankaran, MD-PhD, (elected 2018); member, ASCI Diversity, Equity, and Inclusion Committee

Note: The text has been edited for readability by ASCI staff.

Vijay Sankaran: Welcome to this ASCI Perspectives interview. My name is Vijay Sankaran from Boston Children’s Hospital and Harvard Medical School. It is my distinct pleasure to have as today’s guest for our Perspectives interview Dr. Courtney Fitzhugh. Dr. Fitzhugh is a Lasker Clinical Research Scholar and heads the Laboratory of Early Sickle Cell Mortality Prevention at the National Hear t, Lung, and Blood Institute. She’s a pioneer in advancing the use of hematopoietic stem cell transplantation in sickle cell disease. Dr. Fitzhugh earned her medical degree at the University of California, San Francisco. While in medical school, Dr. Fitzhugh participated in the National Institutes of Health Clinical Research Training Program and worked with John Tisdale during this time. After completing her MD, Dr. Fitzhugh did a combined internal medicine and pediatrics residency at Duke University Medical Center, and then did a combined adult and pediatric hematology fellowship at the NIH and Johns Hopkins Hospital. Dr. Fitzhugh is widely recognized for her groundbreaking studies in applying hematopoietic stem cell transplantation in sickle cell. She’s a member of the American Society of Hematology and a newly inducted member of the American Society for Clinical Investigation. Dr. Fitzhugh, welcome to this Perspectives Interview.

Courtney Fitzhugh: Thank you for having me.

VS: To begin with, I was wondering if you could tell us a bit about yourself, your training path, and what initially got you interested in science and medicine.

DF: Sure. I’m originally from California. I grew up in San Jose, California. My father was a family practitioner, and I used to go with him to the office. I was his medical student — I’m sorry: I was his medical assistant when I was in late high school. I just really loved working with him. I loved that he had those great relationships with his patients, the continuity of care. Initially I wanted to do family medicine, until I went to medical school and realized I was much more interested in taking care of sick people. And so I read about sickle cell disease and just was really excited about it, the fact that it affects children and adults, so I can still have that continuity of care. It impacts any organ system in the body, so everybody is different. And just from reading the pain and the disparities associated, I felt like it was a place where I could make a difference.

And so when I went to medical school, after my first year, I did research in the lab over the summer, and I really liked seeing the patients more than I enjoyed being in the lab. So I really was interested in the clinical aspects of it and got interested in clinical research. As you mentioned, I went to the NIH after my third year of medical school and met John Tisdale, and he gave me the opportunity to work on developing a new curative approach for sickle cell disease. So since then I’ve been hooked.

VS: Wow. That’s amazing. Now you talked about the impact that being a medical assistant for your father had upon you. I was wondering if you could talk a little bit about the impact more broadly about mentors that you’ve had in your career and how this has helped shape the paths you’ve taken as a physician scientist.

DF: Yeah. It’s been critical at every single stage of my career. Going back to John — and I just had such a wonderful time with him: seeing patients, the way that he interacted with the patients, just how caring he was, and how much of an advocate he was — or is — and how committed he is to my success. He’s been incredible, and I’ve had so many different mentors in every single aspect. So I’ve been interested in talking to women and how they balance work-life balance, and then people outside of the NIH who can give some advice. And I’ve really  — That’s one of my favorite things now about having a lab, is actually being able to pour into the next generation and mentor others.

VS: Wow, that’s really great. Along the way, and you sort of alluded to this, it sounds like you’ve described the value of having mentors not just at earlier stages of your training or when you were sort of . . . before you started your training, but actually even now as a laboratory head. And I was wondering if you could comment on the importance that you view of mentorship and how you believe mentoring others can also help in this process as well.

DF: Yeah, mentoring . . . I think one of the best stories I have about mentoring now is: Just recently, I went to a Cure Sickle Cell meeting, and I started talking to Michael DeBaun about my interest in long-term health effects of curative therapies. And just from that discussion, we started a collaboration and applied to — successfully awarded — a U01 award. And so working closely with him and helping me with writing my first grant at this stage of my career was really critical. And now being able to do that for others, helping my trainees with their presentations, with abstracts, with manuscripts, it’s just really fulfilling and exciting, being able to see others succeed.

VS: That’s terrific. That’s really amazing. And it’s really just such a testament to both your own mentors, but also giving back and continuing that process and helping support people.

DF: Thank you.

VS: So I want to switch gears a bit. You have and you continue to contribute tremendously to advance our understanding of how we can apply hematopoietic stem cell transplantation using allogeneic and autologous sources to cure sickle cell disease. This has been an exciting area, with lots of recent activity. Could you tell us about where you see this research field going in the coming years and what advances that you’ve been most excited about?

DF: Yeah. This is a real critical time not only just for curative therapies. I remember when I first went to my first American Society of Hematology meeting, you would hardly see anything about sickle cell; it was very few and far between. And now, there’s so much, I can’t even get to it all. So, just in the short period of time that I’ve been in the field, seeing how much transformation, all the new drugs that have been FDA approved or are being developed — but in the curative therapy setting, it’s really exciting. As you mentioned, we have both allogeneic and autologous approaches. Unfortunately, the most successful traditionally has been HLA-matched sibling transplant, but less than 15% of sickle cell patients have an HLA-matched sibling donor. So what are the options that are available for others? So, now we have haploidentical transplant, where you increase the chance they have a donor to 90%, because most patients will have a parent or a child or half-sibling who could serve as a donor, or even you could use cousins and nephews and nieces. So that increases the donor pool, and there’s been some exciting new discoveries and new conditioning of regimens that have been successful — and even in the haploidentical setting with results that are approaching the HLA-matched sibling setting. So that’s been really exciting for me, since that’s my interest. And now what I’m trying to do is apply these exciting results to patients who have compromised organ function, who are very frequently left out of clinical trials. In the gene therapy and gene editing areas, there’s also a lot of excitement there too. The biggest limitation is that they use high-dose chemotherapy for these gene-corrected cells to be able to have the advantage. What is exciting in that field is using antibody-based conditioning in order to clear out the patient’s own autologous cells.

So whenever they get that to work, that’s going to be a really exciting endeavor. And then in vivo gene therapy, where they won’t have to do a lot of the manipulation outside the lab, but just being able to inject the cells and ideally cure them that way. So that would give a lot of patients, hopefully even outside of the US, access to this care. So I just love . . . Because people ask me, “What’s the future for haploidentical transplant in the setting of gene therapy and gene editing?” But I just think it’s so great that the patients have these options to choose from. There’s pros and cons for both, and right now we don’t even know the short-term or even the long-term success and toxicity associated with these approaches. A lot more work is done, and I’m excited to be able to work some to contribute to that field as well as others.

VS: Wow, that’s tremendously exciting. I want to also go back to something you mentioned earlier when you were talking about mentors, and you were talking about your work with Mike DeBaun and this recent U01. And it sounds like this was focused around long-term complications of some of these therapies. And I was wondering if you could comment a little bit, because I know you’ve thought a lot about this issue, about what we also need to do and where more research is needed in that space.

DF: Yeah. Thank you for asking. So we’re really interested in how . . . We’re not just trying to cure the patients in the short term. We’re trying to reverse their disease and help them to have a wonderful quality and quantity of life that’s long-term. Unfortunately, a lot of times, the patients are transplanted, and then they’re referred back to their doctors and sometimes they’re not followed for the long term. We really don’t know what’s happening to these patients. So we’ve tried to get some of the biggest transplant institutions together, which includes Children’s National Hospital in DC, Vanderbilt of course, NIH, Emory, and Hopkins. And to look to see, looking not only at the survival, graft-versus-host disease, which a lot of people look at, but what’s happening to the heart, the lung, the kidneys. These organs when damaged lead to early mortality in adults with sickle cell disease.

But we’re also excited that we’re going to be able to compare how nonmyeloablative or the lower-intensity conditioning compares with myeloablative conditioning, transplanting adults versus transplanting children, doing transplant versus standard therapy, not transplanting them — and be able to follow these patients. We’re going to have about 20 years of data between the retrospective and the prospective collection of the data and reporting of the data. So we’re really excited to see — and this is the only way we’re . . . And we’re also including people who have undergone gene therapy and gene editing. So I’m really excited to see what we’re going to find.

VS: Wow, that sounds incredibly important. And also just so needed, because while there’s so much excitement around these emerging approaches, obviously there’s a lot of work to be done to understand, what are the long-term consequences of all of these changes. So that’s tremendously important. So I want to move on to a slightly different area. Many of our viewers of the series are likely physician-scientist trainees, including those from traditionally underrepresented backgrounds in medicine and science. I was wondering if you could comment on lessons you’ve learned in your own training as a physician-scientist and what advice you might give to trainees who are watching this interview.

DF: So I would say, one of the most important things is just to realize what you’re passionate about, what excites you. Because I love going to work every day because I’m so excited about what I do. So it’s not really about making the money or where you’re going to make the most money, but where are you going to be happy? Where are you going to be able to make a difference? And I’d also say just to . . . I used to struggle with imposter syndrome. I came to the NIH because I wanted to work with John Tisdale. I wanted to support his research, and that door was not open to me. He only had one position, and it was already filled. But this other door swung wide open, and if I had had fear and didn’t walk through, I wouldn’t be where I am. I would say look for those doors. Where are those doors opening? So that all you have to do is just walk through. And then look to see what success you’ll have and how you’ll be able to make a difference in the lives of your patients and others.

VS: Wow, that’s such great advice. And I think even today it’s such an important thing that I as I think about different opportunities always, it’s hard to get perspective on that. So this has been such an enlightening and fantastic discussion, Dr. Fitzhugh. I was wondering if you could provide us with some closing thoughts for this audience and any other thoughts that you might have about the work that you’re doing or areas that physician-scientists can think about as they develop.

DF: Yeah. I just love being able to be an advocate for my patients with sickle cell. A lot of them go to the emergency room, and no matter where they are in the US or even outside the US, they’re treated like . . . people don’t believe that they’re having the pain. And it’s just so frustrating and disappointing hearing the same story from the patients over and over. But being able to develop relationships with these patients, develop trust with these patients, and then offer them an opportunity to have a new life that doesn’t involve pain and fatigue. And it’s just  so wonderful. So just look for the way that you’re going to be able to make a difference in the lives of your patients.

VS: Well, thank you so much, Dr. Fitzhugh. It has been truly outstanding to be able to chat with you today.

DF: Thank you for inviting me. I appreciate it.

Interview with Juan Pablo Arroyo, MD, PhD, Vanderbilt University Medical Center (recipient, 2022 ASCI Emerging Generation Award)
Interviewed by Jennifer S. Yu, MD, PhD (elected 20218); member, ASCI Diversity, Equity, and Inclusion Committee

Note: The text has been edited for readability by ASCI staff.

Jennifer S. Yu: Good afternoon and welcome to the ASCI Perspectives. I am Dr. Jennifer Yu from the Cleveland Clinic, and today my guest is Dr. Juan Pablo Arroyo. Dr. Arroyo is an Assistant Professor of Medicine at Vanderbilt University. His research has focused on understanding fluid dynamics and their regulation of metabolic diseases. Dr. Arroyo is a recipient of the ASCI Emerging-Generation Award in 2022. He is also the recipient of the 2020 Robert Wood Johnson Foundation Amos Faculty Development Scholar award. Dr. Arroyo, thank you for taking the time to speak with us today and sharing your words of wisdom.

Juan Pablo Arroyo: Thanks so much for the invitation. I’m really happy to be here.

JSY: You had an interesting path to becoming a physician-scientist. You obtained your MD at the Universidad La Salle in Mexico and followed that up with a PhD. Was there something in particular that attracted you to this career path?

JPA: I’ve been a little bit of bouncing around. I started medical school in Mexico. You just do six and a half years straight out of high school. And I met my physiology professor — he’s a basic scientist, and he basically taught me to love physiology. And once I finished my MD, I was dead set on becoming a surgeon in the US because of some rotations that I had. And I had a required year of research that I was doing, and I was in his lab and I just loved it. So I ended up getting a PhD in kidney physiology. And it was basically for the love of understanding why things happen the way they do, more so the diseases; it was understanding how the body works. Never second-guessed the surgeon part. And I ended up doing so: I did the MD, then I did the PhD. And then I got a prelim position as a general surgery resident at Yale. I did a year there, and after that I realized surgery was definitely not for me. So I ended up doing a two-year postdoc in renal genetics and hypertension in Rick Lifton’s lab. And that was an amazing experience that taught me an enormous amount.

And after that I came to Vanderbilt, where I’m at, and I did the physician-scientist training program. So I did two years of internal medicine, the year of clinical nephrology, and then I was asked to be a chief resident. I was a chief resident for a year, then went back into the lab, started research, and then got promoted to faculty. So it’s been a little bit of a circuitous path to get to where I am now.

JSY: Wonderful. And it really speaks to how teachers can be so inspiring to students and how they can really change your trajectory.

JPA: Oh, 100%.

JSY: And I’m so glad you followed your heart and decided what was most important to you and most interesting to you. So let’s hear a little bit about your research. Our bodies are comprised largely of water, and your research focuses on water dynamics and links to metabolic diseases. Can you tell us a little bit more?

JPA: So when I was a surgery resident, I was on the thoracic surgery service. And a clinical observation was that a lot of the patients undergoing thoracic surgery that didn’t have any preexisting conditions — they were going for a wide resection or some . . . it’s major surgery, but they were going for surgery, And I was told as the intern that I had to keep them negative. So I had to give them Lasix and make sure that they didn’t stay . . . their eyes and nose weren’t positive. I was fresh out of my PhD, and I was like, “Why am I giving these people Lasix?” And it always bugged me that we were given the diuretics, and I didn’t understand the physiology: Why were these people producing antidiuretic hormone? Because that’s the problem. If you don’t give them diuretics, then they can develop hyponatremia, low serum sodium. And that sort of stuck with me: Why is this happening? Why is this happening?

And then I kept asking the question “Could the vasopressin be coming from somewhere else, not just the brain?” Because the explanation has been like, “Oh, everybody gets . . . the body gets stressed, and the hypothalamus produces the vasopressin.” I’m like, “I don’t know if that works out.” And I continued to follow that. And then when I came to Vanderbilt and was studying nephrology landed on polycystic kidney disease and realized, “Well, they have high vasopressin levels as well, and this is driving disease — is this all coming from the hypothalamus?” So then I started on my research, and my research career has been built initially on understanding how vasopressin works and showing that vasopressin is not just made by the brain. We were lucky enough to publish in JCI insight in 2022 that vasopressin is made in the kidney. So functional vasopressin is coming from the kidney.

The physiological relevance is what we’re working on now. But that goes to show that . . . what we’re interested in is that if each cell has the ability to regulate its own water metabolism, and water metabolism is intimately linked to glucose regulation and fat metabolism and bioenergetics, then is there anything else that we’re missing in terms of understanding how water can change our internal environment? So that’s the current focus of the lab. And again: a circuitous route to get to where we are now. But I’m incredibly excited about the work that we’re doing.

JSY: How fascinating. Well, thank you for sharing how you came upon that — just asking questions of patients in your patient care and how that really led to your research in vasopressin. Many people are working to reduce bias in the workplace, and you have advocated to eliminate the requirement of applicants to provide their pictures in their ERAS [Electronic Residency Application Service] application for residencies. Can you expand on that?

JPA: So initially I got the opportunity to be a chief resident for the Vanderbilt Internal Medicine program. And we were doing a lot of these interviews, and this was I think 2018 to 2019. And this was — we were doing in-person interviews and reviewing the files. And initially when we were reviewing the files, the way that you download the ERAS documents, the first thing that would pop up was a picture. And I would find that when we were doing evaluations, the first thing you see is the picture. And that to me just sends the . . . you have a preconceived notion of what this person is or isn’t. And I started looking into some of the data, and there’s actually data that the picture can definitely bias how you see an application.

So what we decided to do is, we came up with a more comprehensive system to evaluate applicants. We have a pretty thorough spreadsheet, like a data set that we go through and we evaluate on multiple levels. And we eliminated some of the test scores and we focus on who this person is and what their trajectory this far has been. And the whole point was trying to evaluate everybody the same way. So eliminate bias in either direction and making sure that we’re evaluating the best people for the job regardless of any other factors. So that’s encouraging.

JSY: That’s great to hear. Do you know if other institutions have also rolled out a similar policy not to look at those pictures?

JPA: I know that some do. I think it’s relatively informal so far. Some people, some institutions have been doing it for a while, and others have started adopting it. I don’t know of any formal mandate to do it, which is why we wrote that letter to the editor that got published in Academic Medicine calling for ERAS to just: let’s just do this nationwide. Because again, it’s not about highlighting someone and pushing someone else down. Just basically leveling the playing field for everybody, making sure that the attributes that we care about for physicians are the ones that are highlighted when someone’s applying for an interview. So: Not formally, but hopefully we’ll get there.

JSY: Yeah, well it’s a big step in the right direction. Thank you. Can you share with us some words of advice for those perceiving bias, either conscious or unconscious, in the workplace?

JPA: My own experience has been . . . What has worked for me is I always try to assume that everybody is doing the best they can with what they have. Period. If someone is upset for a particular reason, and yelling is what they can, then that’s the best they can do with the emotional, psychological tools and everything that they have right then and there. So me coming from the position that that is the best I can get from that person right here and right now leads me to then treat everybody with more kindness and respect. Because I don’t automatically assume that they’re out to get me. Because I think that starting there makes everything a little bit harder. So just assuming that whatever reaction is the best that that person can give you right then and there makes everything a little bit easier.

JSY: Great. I really like how you say you treat everyone with kindness — kindness and respect — which is easier said than done sometimes, but great.

JPA: Yeah, definitely. I mean, I can tell you that because of my last name. So I have four names, and something that we are discussing, right? My name is, John Paul — in Spanish, Juan Pablo — and I have two last names, my mom and my dad, Arroyo Ornelas. So my full name is Juan Pablo Arroyo Ornelas. So sometimes when I’m seeing patients, they’ll look at my name and they’re like, “What’s your name? Where are you from? You’re not from” around here.” And I tell them, “No, I’m not. And generally what I — again coming back to this “Treat everybody with kindness” is when I’m meeting a patient, particularly in nephrology, I’m the kind of doctor you don’t want to meet, right? So everybody’s going to be afraid. That’s it. So if they’re scared and I meet the patient when they’re scared, everybody, and this includes myself, everybody tends to be scared of difference. And if there’s something different in a stressful situation, of course, tempers will flare. So again, going back to the “Everybody’s trying the best they can with what they have,” I go back to the patient and I explain, “Yeah, I’m not from around here, this is this.” And I give them a little bit of background. And that always has helped.

JSY: Great. Well, words to live by: treat everyone with kindness. We have many early-career scientists who watch our program. Can you tell us a few words of wisdom, lessons that you’ve learned during your career journey?

JPA: I think one of the biggest lessons that I’ve learned is I thought in the beginning that I needed to have everything figured out and, you’ll hear this a lot, that the trajectory is linear. And you can see, so from my career trajectory, nothing has been linear at all. I started off as wanting to do general surgery or general surgeon in Mexico, and now I’m a nephrologist that’s an academic scientist in Nashville. It’s not linear.

So what I would say is that same kindness that I try to show to others in terms of they’re doing the best they can with what they have, I try to do that with myself. I’m doing the best I can with what I have. And if the best I have right now is, like, the best I can do right now is just sit down in front of the TV and watch a show, because I don’t have the emotional strength to deal with either writing the paper, writing the grants, and I just can’t. And what I can do right now is make the conscious choice of: I’m going to sit down and I’m going to watch a movie with my kids. Okay. That’s what I can give. And that same kindness, sort of bring it on myself. I think that that’s the best advice that I can give, because specific advice in terms of like, “Learn this technique” or “Learn this other thing” or when to apply for a grant — what I’ve realized with myself is that the best thing that I can do is take advantage of the tools that I have to give and that I can bring to the world. Right? So if I’m in a really good place where I can push myself a little bit harder, I will try. And then if I fail, I’m like, “All right, well, I tried.” But again, that same kindness that I try to show to other people reflected on myself.

And I think that we need to learn to deal with failure a lot in science. And from the junior faculty’s perspective, I’m not good with failure, I’m not good with rejection, and I’m always paranoid. I have terrible imposter syndrome. And all I try is like, “I’m going to try my best and be kind with myself every time that I try my best.” And that’s it. That’s the best advice that I can give. Not necessarily field-specific, but just be kind.

JSY: Thank you. That was so important for you to say, to be kind to yourself. And it sounds like you’re very introspective as well, which is really important in our field and in many other fields as well. And you also talked about resiliency, especially as a physician-scientist taking care of sick patients as well. It’s tough. So it’s important to reexamine yourself and step back when you need to. And lean in when you need to. Well, thank you so much for sharing your words of wisdom today, your experience. It’s very informative, and I think will help a lot of our viewers. Thank you.

JPA: No, you’re very welcome. I’m very thankful to have had this opportunity to talk with you and I hope I’m able to help someone with this.

JSY: I’m sure you will be able to — many, many people. Thank you.

JPA: You’re very welcome.

Interview with Neil A. Hanchard, MBBS, DPhil, National Human Genome Research Institute, NIH (elected 2022)
Interviewed by Vijay Sankaran, MD, PhD (elected 20218); member, ASCI Diversity, Equity, and Inclusion Committee

Note: The text has been edited for readability by ASCI staff.

Vijay Sankaran: Welcome to this ASCI Perspectives interview. My name is Vijay Sankaran from Boston Children’s Hospital and Harvard Medical School. It is my distinct pleasure to have as today’s guest for our Perspectives interview Dr. Neil Hanchard. Dr. Hanchard is a Senior Investigator at the Center for Precision Health Research at the National Human Genome Research Institute at the National Institutes of Health. He received his medical degree with honors from the University of the West Indies in Kingston, Jamaica, and then completed his Doctor of Philosophy in Human Genetics from the University of Oxford as a Rhodes Scholar. At Oxford, he worked with the late Professor Dominic Kwiatkowski on genetic variation impacting the major histocompatibility complex. He then completed his training in general pediatrics at the Mayo Clinic, followed by a medical genetics fellowship at Baylor College of Medicine. He then started his lab at Baylor for several years before moving to the NIH in 2021.

Dr. Hanchard’s work has helped to define the genetic causes for a range of rare diseases, while also identifying factors that cause variation in more common diseases such as sickle-cell disease. He has received extensive recognition for his work, including being elected to the American Society for Clinical Investigation in 2022. Dr. Hanchard is currently Chair of the Genome Analysis Working Group of the H3Africa Consortium and an NIH Distinguished Scholar. Dr. Hanchard, welcome to this Perspectives interview.

Neil A. Hanchard: It’s an honor to be here.

VS: Well, great to have you. To begin with, I was wondering if you could tell us a bit about yourself, your training path, and what initially got you interested in science and medicine.

NAH: I guess I have a somewhat unusual training path compared to many in that I did my medicine, as you said, in Jamaica, which is where I’m from, which is where I grew up. And following that, I won this Rhodes Scholarship, and the scholarship couldn’t be used to do, say, postgraduate training, which is what I was interested in at that time. And so, they said, “Ycou probably need to do some research.” And I looked around for something that had something to do with pediatrics, and the available project had to do with genetic susceptibility to prematurity. And I was always fascinated by genetics and thought it really interesting. But that was really my first interaction with research at a bench level.

And so that was an opportunity that completely changed the trajectory of where I ended up being, and it was an [was able] to make the most of. And so while in Oxford, I got into genetics and I loved it. It was a great explanation for why things happened and so much more definitive. This was also around the time when the Human Genome Project was finishing. So there was all this incredible excitement about the potential to be able to dissect complex traits and other diseases. And so it was a case of really good timing and an incredible opportunity. And so that’s kind of . . . Once you’ve had the wool taken off of your eyes, you’re like,” Whoa, this is really something incredible that I can participate in.”

VS: Wow. It’s so exciting to hear about how in some ways it was serendipitous, that you encountered genetics in some ways and that took you in a new direction. Could you talk about the impact that mentors have had in your career, in shaping these different transitions, and that have helped you to shape your path as a physician-scientist?

NAH: I think I’ve had the good fortune to interact with a number of really strong mentors who are somewhat atypical in that they’re all physicians and physician-scientists, but they also all had a very clear view of what they wanted to achieve. For instance, Professor Kwiatkowski, who recently passed along, he just wanted to understand malaria and why children got malaria and died from malaria. But what was really insightful for me was the way in which he went about it. He did it with a kind of grace and kindness that, I’ve since learned, discovered, is not something you find everywhere. And so that’s something that I’ve tried to emulate in the way in which I approach my own mentorship of those who are in my lab and those who I interact with as collaborators.

And I had the same thing after I finished my PhD. I’d gone back to Jamaica for a while and worked with Colin McKenzie, who was also a PhD physician-scientist. And he had the same idea and mentality about how we’re doing these things. And then most recently while I was at Baylor, I was mentored by John Belmont, who’s another physician-scientist, again, very focused on thinking about the patients and why we’re doing this and how it is that we can actually improve things in that regard. And I’ll also say that they were the de facto mentor mentors for me as I went through. But along the way, you had the opportunity to interact with others in that sphere who gave you a different perspective and helped you to understand a little bit more about maybe aspects of it that weren’t just pure academics.

So they understood how to network or how to maneuver within academia, and when to press go, when to stop, when to go forward. And those kind of interactions and seeing others in their interactions have been really, really valuable. Some of this came through the H3Africa project that you mentioned that gave me another opportunity to work closely with mentors at Baylor — Chester Brown and Graham Martin — but also to see the other side of the world and learn from researchers who are in very different circumstances and in very different environments. And I think all of those experiences play into my current approach and the way that we’re thinking about problems and approaching them now.

VS: That’s fascinating. It’s really great to hear, and I think something that we often hear from in these interviews is the role that different mentors have had along the way, both formal and informal. And it’s really exciting to hear about how that’s helped you in your own career and in your path. So then moving to your career a bit, you have and you continue to contribute tremendously to advance our understanding of how genetic variation can impact the risk of both common and rare disorders. Could you tell us a little bit more about where you see this research field going broadly in the coming years?

NAH: I think that the primary focus of the last, I don’t know, 10 years or so has really been on the discovery side of things. We’re trying to understand associations and trying to identify genes that are, say, responsible for rare disorders. I think that we’re in this transition period where now we’re trying to understand what those associations mean and how can we pull the causality out of those associations. And part of that has to do with trying to really understand how variation has these impacts. And so that means that we have to understand the in-between of, like, here is a variant and here is a phenotype, and getting a better hold of “This variant changes something in transcription or in translation or in the proteins” and see that whole progression and how that relates to a particular disease outcome or disease trait.

So I think that as we start to understand, particularly for these complex traits, how the noncoding variation impacts regulation and impacts diseases, I think that’s gonna be the current phase in which we’re in to try and really understand. And then the big corner turn is going to be whether we can make this get a way back to the patient. And so I’m really excited, particularly for Mendelian diseases, to see that there is this kind of shift and change where people are now starting to look at like, “How can we actually treat some of these rare disorders?” Now that we have a much better understanding, it’s easier with coding variants or single-gene variants that have a really large effect upon the phenotype. But how can we then translate that into something therapeutic?

And that’s really exciting, because one of the frustrations often is that you’d interact with patients and you’d feel really chuffed. You’re like, “Oh, I’ve discovered the cause of your disorder,” and they would say, “That’s great, but what are you going to do about it?” And so I I’m really buoyed by the idea that we’re perhaps thinking more about getting this back from the bench to the bedside from a therapeutic standpoint, particularly for rare diseases. And that as we get a better handle on how the genome works, we can maybe start to make some inroads in that regard for complex diseases as well.

VS: That’s really fascinating. So in addition, you’ve been a major advocate for the need to increase diversity in genetics research. And I wondered if you could comment a bit on how we can achieve improved diversity in the field of genetics and maybe more generally in biomedical research.

NAH: I think that I’ve been fortunate enough to have the opportunity to interact a lot with folks who are at the forefront of this. And the kind of lessons that they have taught me and that I’m taking away is that we just of have a multipronged approach to this. It’s not just who we study. So diversifying the research cohorts that we interact with, who the references or the individuals that constitute the references for genome variation, for instance — that’s a big part of it. But it’s also who does the studying. So one of the big things about trying to engage communities to be a part of research is that it helps when it’s someone from their community who is doing that research.

And so there is both a community researcher part but then also the researchers themselves. And having this across this entire spectrum that we are mindful of the importance of being diverse in our viewpoint. And I think that one of the keys to that is community engagement. And I think this is where it’s not just true for genetics and genomics, but also across biomedical research; that in order to enact all of this, we’re going to need to have good community engagement — where we’re listening to how communities want to be approached, what’s important to communities, and how it is that we can work together in order to get to a point where the research we do, the medications that we give, all of these things are good for all and not just for a subset of individuals.

VS: So I’d like to change gears a bit. Many of our viewers of the series are likely to be physician-scientist trainees, including those from traditionally underrepresented backgrounds in medicine and science. So I was wondering if you could comment a bit on the lessons you have learned in your own training as a physician-scientist and what advice you might give to trainees who are watching this interview.

NAH: I thought about that, and I’ve given this some thought in the past. I think one of the things that I am acutely aware of as a physician-scientist is sitting in this kind of in-between portion, where on one hand you have scientists and science and then you have the physician and the patients. And there’s a niche group of us who sit in between those two groups. And that gives you a very valuable insight to things because it allows you to have a certain focus about what you’re trying to do and whom you’re trying to do this for. But it also brings a way in which you can actually do that, right? So I think that sitting at that interface is really key, and not to be undervalued.

The flip side of those is that there are challenges, and being in that in- between is that often you don’t necessarily get the recognition that, you don’t have the same viewpoint as, say, a scientist who is working on it. And necessarily, if you’re trying to do two things, you’re not doing quite as much. And on the other hand, you may never be a master physician because you’re trying to sit at that interface. And I think for many physician-scientist trainees whom I’ve spoken to, that dichotomy is something that they have struggled with. And I think what I’ve tried to get across to them is to try and embrace that, because it is still a valuable place to be. And it is the way in which we’re going to get from one to the other. It’s an important place to be in and not to be dissuaded from trying to sit at that interface, although it is admittedly sometimes particularly difficult.

VS: That’s really, really inspiring. And I guess the other question I’d love to follow up on, just related to what we had discussed earlier in this interview was you talked about the role that mentors have had and their generosity. As many of the trainees who might be watching this interview are thinking about “How do I identify mentors or get to know mentors,” I was wondering if you had advice there that could help them as they’re seeking that process.

NAH: I can only speak, I guess, to the kinds of experiences I’ve had. I think I’ve been very fortunate to have mentors who shared very similar ideals, particularly in terms of science and a physician-scientist type of approach to things. And that’s been very helpful for me. So I think finding your people, so to speak, is actually really important. Sometimes that can be at meetings and figuring out which meeting is your meeting, where are your people? And so identifying who your people are, who will be supportive of the work you’re doing or the approaches that you’re taking, and how you go about and think of things is something to put high on the list of consideration. But I also think that being open to being mentored outside of just your immediate supervisor is also really important: thinking about mentors who may not know your work at all, but may have useful insight about how you navigate the academic world and the kinds of decisions that inevitably come down through these kinds of efforts that need to be made, and what are the kind of pros and cons that go into making those decisions. And I found that having some of these people who aren’t my direct supervisors but who are confidants who you can run stuff by actually has been really insightful and helpful. I think the other thing about choosing a mentor is that senior people, who often have the keys to the kingdom, they are often pretty busy. And so it’s important that your mentor can have the time to be able to do this, and some people don’t have the time, and it’s not because they don’t want to, it’s just the practicalities of life.

But it’s also a lesson to not put all your eggs in one basket, right? So if you have a group of mentors whom you’re not necessarily pulling upon an extensive amount of time from one individual, you’re much more likely to get what you need through a group of individuals just because you kind of spread the same effort over many individuals.

VS: Well, this has been an enlightening and fantastic discussion. I was wondering if you could provide some closing thoughts for the audience.

NAH: I think that the things that I am in the middle of now are this idea that, particularly as physician-scientists, we are in a position to enact sea changes where sea changes need to be enacted. And that’s not a position to be taken lightly, but it is something that can be done particularly in terms of some of the diversity efforts that I’ve been involved with, but also in terms of back-to-the-bedside type of activities that, again, I feel are really important. And we are in a position to ensure that that stays as cutting edge as it needs to stay in the sense that we don’t have to do everything the same way that everybody’s been doing it for the last 50 years. But it’s important to know what’s been done for the last 50 years.

But I think there’s just incredible opportunities now, especially with the big data and data sciences that are expanding, to really have a big effect and to enact these kind of big environmental shifts that are needed, to push medicine in general, and for me personally, genomic medicine forward.

VS: Well, thank you so much, Dr. Hanchard. It has truly been outstanding to be able to chat with you today.

NAH: Thank you so much. It’s been wonderful to be here, and I’ve really enjoyed chatting.