Devin O’Brien-Coon, MD, is an advocate for his patients, a biomedical engineer who explores cutting-edge techniques and a surgeon who has transformed patients’ lives. But to many of his patients and colleagues, he is simply “DOC.” O’Brien-Coon joined the Brigham in November 2021 and is establishing both his lab and clinical practice at the Brigham, where he serves as clinical director and surgical co-director of the Center for Transgender Health. The center’s multi-disciplinary team, led by O’Brien-Coon and Shalender Bhasin, MD, provides personalized care for patients that’s designed to meet their goals and needs. Leveraging 3D technology, tissue engineering and biomedical engineering, the team can perform even the most complex reconstructive surgeries, including complicated revision cases. In addition to directly caring for patients, O’Brien-Coon develops surgical techniques and conducts research to help advance the field.

O’Brien-Coon sat down with Clinical & Research News to answer questions about innovation, research and his dedication to helping patients.

Q: What are some of the biggest biomedical engineering challenges in performing gender affirming surgery?

DOC: Fundamentally, the biggest challenge is the nature of the goal. Most of what we do in reconstructive surgery is restoring or replacing part of something that has been lost. But with gender-affirming surgery, we’re setting out to create new organs. And it not only needs to look natural, there are also critical functional needs, such as a new urethra that enables voiding or sexual function. The technical demands to achieve all that require new approaches, and so this is an emerging field.

Q: What are some of the emerging solutions?

DOC: For many years in reconstructive surgery, it’s been argued that there are two horses in a race: tissue engineering and transplantation. I think both are potential paths forward. I was part of the team at Johns Hopkins where we did the first total penis and scrotum transplant in 2018. While transplantation is here now and works, the main disadvantage is patients must be on low-dose immune suppression regimens for the rest of their lives, which increases the risk of cancer and other diseases. This is unlikely to change until the entire field of transplantation medicine finds a way to overcome rejection and means that transplant will generally remain a last resort. Tissue engineering avoids those immunosuppressive risks but the challenge is finding a way to ensure blood supply to support a large organ structure. For some kinds of tissue engineering needs, such as replacing pancreatic islet cells for a patient with diabetes, it’s just supplying blood to a small cluster of cells that can live off diffusion. But in gender-affirming surgery, the scale is much larger. My lab developed the first decellularized whole-organ penile scaffold as a first step in this direction, but finding a solution to re-vascularize it when it’s deployed is undoubtedly a much longer term effort.

Q: Can you tell us more about your studies of the effect of sex hormones on wound healing? How might understanding this connection inform surgical planning?

DOC: That’s perhaps the most exciting lab thing we’re working on right now. One of the things I became interested in over time was how hormone regimens can affect wound healing and scarring because it seemed like some of my patients on hormone therapies had different outcomes than my other patients. That led us to questions we could begin exploring in the lab. We’ve started to see that hormone therapy may induce differences and that testosterone may make wounds more inflammatory so they are less likely to heal and then when they do heal the scarring is wider and more dense. There may even be a difference in how testosterone affects wound healing if you have an X or Y chromosome. We have several preclinical models we’re studying, and some patients have begun participating in clinical trials to further examine this.

Q: Who are some of your collaborators at the Brigham and beyond?

DOC: Research collaborations on sex biology, hormones and wound healing were part of what drew me to Boston — this is arguably the hotspot for this subject. I work closely with Dr. Bhasin — he practically wrote the work on testosterone biology. He’s been great to have as a collaborator in understanding new, unappreciated effects of sex hormones. We’re looking for more opportunities for synergy between the Center for Transgender Health and the Boston Claude D. Pepper Older Americans Independence Center, since the biology of aging, sex hormones and how the two interact is fascinating and we are starting to learn completely new things from patients on gender-affirming hormone therapy. These discoveries may have great clinical relevance as both the elderly population and the transgender and gender diverse (TGD) population continue to grow rapidly.

I’ve also been working with Dennis Orgill, MD, PhD, who has been a pioneer in wound healing for 30 years and a key collaborator. Ultimately, we want to understand the effects of hormones on wound healing so that we can find a way to reverse it or control it for patient benefit. This research may not only help patients undergoing gender-affirming surgery, but others — such as elderly or diabetic patients — who may have wounds that heal slowly or scar poorly. We’re also interested in exploring the role of the immune system, whose long reach extends to wound healing. And across the river at the Whitehead Institute, we collaborate with David Page, MD, who was the first to map the Y chromosome and has redefined our understanding of the biologic mechanisms of sex differences. His lab has shown that evolution has led to complex variation between males and females for much more of our basic bodily physiology than anyone ever expected. We are working with his group to understand the mechanisms driving differences in how people respond differently to sex hormones (e.g., testosterone) based on their sex chromosome complement (i.e., XX vs. XY).

Q: What educational efforts are planned or underway?

DOC: We have an educational fellowship in gender-affirming surgery that will begin this July and Dr. Bhasin and Sari Reisner, ScD, director of research for the CTH and a national leader in clinical research with TGD populations, are working to obtain additional funding to train people to advance research in this area. We may also track an endocrinology fellow to work with the Center. Training clinical providers and researchers alike will be a big focus for us.

This story is part of our “Lead the Change” series, an ongoing series that focuses on issues related to public policy, advocacy, and timely societal challenges. Through stories, viewpoints and events, experts from across the Brigham share their experiences and perspectives. Find information on monthly forums for Brigham employees on PikeNotes. Join the conversation and get inspired to lead the change toward a healthier, more compassionate and more engaged world.

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