Transcript of ASCI Perspectives – Fitzhugh interview

Interview with Dr. 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.