Moving from Known to Unknown

by AWS Research Fellow,  Holly Lewis MD PhD

I wish to thank the Association of Women Surgeons, its members and sponsors, who awarded me its research fellowship this past year for our project, An Injectable Biomaterial for Transplant Tolerance. To thank all the mentors and sponsors I’ve had along the way would take far more space than I’m allotted, so I will share some words of reflection.  In college, my passions for chemistry and biology were buttressed by lab experiences at a number of institutions around Boston. I became fascinated with the immune system, and how it could be harnessed or redirected in health & disease. As the child of a kidney transplant recipient, I watched my Dad develop several malignancies in the setting of immunosuppression; I wondered how we could improve. In medical school, determination to become a surgeon precipitated after my PhD many tissue engineering-based therapies I’d studied were being deployed every day in our operating rooms.  Surgeons were ‘in the room where it happens’ – holding the pathology in our hands, deciding what to do based on a composite understanding of prior literature, personal & collective expertise – extrapolation of what was known into what could be done. In surgical dissection of difficult planes we are often taught to move from safe to unsafe, moving from what is known --  to what is unknown. The onus is upon us to do the work up-front – just as it’s essential to understand the surgical anatomy before the approach.

Early in my prelim surgical internship, I sought a meeting with Prof Tatiana Segura;  in grad school, I’d begun following her groundbreaking work, developing biomaterials with novel regenerative and immune-modifying properties. Unsure if I’d get to stay in general surgery or even become eligible for a postdoc, I met with her to explore those possibilities, and discussed cross-cutting topics in wound healing, chemistry, transplant & reconstructive surgery. Over months that followed, I was offered a position in categorical residency and as PGY2, applied for and won postdoc funding. Dr. Segura and her team supported me at each step, allowing me to do pilot experiments with her grad students on nights/weekends– while a pandemic swirled. In my postdoc, I was immersed in materials engineering – syntheses at the sub-micron level, developing new mouse models for skin graft transplant and more. It was an experience of tremendous growth, supported by a diverse team of lab colleagues. With further support from surgical mentors, we arranged a transition into plastic surgery when I exited lab, as my career goals had shifted toward reconstruction – which I began to see as a clinical application of tissue engineering. With that shift came a calling to pursue new challenges: flaps, hand, craniofacial surgery and more. While internal funding allowed us to hire a full-time technician to support me during me clinical work, I did not yet have my own funding, reinforcing to me a fundamental reality: research simply cannot continue without investment. Being eligible to apply and ultimately win this grant was an amazing gift, ensuring our project could continue.

Thanks to AWS funding, we’ve shown how our materials modify transplant immunity, reducing donor-specific antibodies, tipping localized and central immune responses toward tolerance. We’re exploring small molecules and immune drugs delivered in our material – pushing towards a future with site-specific, mechanism-specific personalized therapeutics. Manuscripts are in preparation, patents are pending, and each day grad students push our biomaterials even further in animal models of stroke, transplant and cancer. With generous support from AWS, Duke Surgery and Engineering; all of this work is truly made possible by Prof. Segura, who invested in me early in my training. Along with Dr. Segura, there are several key surgeons who have made this a reality – many inspirational figures are women in plastics or general surgery but importantly, many aren’t.  One of my favorite parts of plastic surgery is how we collaborate with diverse specialties, operating on ‘the skin and its contents,’ to quote a mentor.  We have so much to learn from those around us, even if we don’t see it at first. Long-ago mentored by an afficionado of surgical instrument history, I now enjoy using eponymous tools, musing that despite their historical inventions for ENT, OMFS, or surgery of the spine, foot or ankle – how much more broadly they’re used today.

Moreover, being part of the Duke AWS chapter has been such a rewarding aspect of my training. As resident liaison, I’ve had the chance to mentor many female- and nonbinary-identifying individuals in matters clinical, academic and personal. I share in their joys, matching into general surgery, plastics, orthopedics or otolaryngology. One of my favorite parts of AWS is how our organization transcends ‘traditional’ boundaries – inviting all surgical practitioners into the tent. Together, we’ve published on gender disparities in grand rounds speakers, pandemic-era telemedicine and values-based decision making by NRMP surgical applicants. The opportunity to attend the AWS meeting this fall in San Francisco was inspiring at every moment. At a workshop with female midcareer faculty, chiefs and chairs, I learned about the power of contract negotiation, and the importance of knowing your value as a surgeon. I had the honor to share technical updates of our lab’s research, inspired by those with whom I shared the podium: surgeons and advocates like Dr. Kemi Doll, or global leaders in surgery, public health and translational medicine: mothers, daughters and nonbinary people. Amongst it all, important conversations with medical students, seeing in each a glimmer of my former self, hopeful but uncertain of the future.

As a premed student, I don’t think I could have imagined the life I’m living as a surgeon-scientist-resident: moving between the anatomy lab where I practice new approaches, research meetings at the engineering school, the ED where I manage plastics trauma on call, the OR as a senior resident, or the clinic, caring for those who have entrusted their health to us. When I connect with mentors who seem to be ‘doing it all,’ I am humbled to realize none of us quite have ‘it all’ figured out.  We are all triaging to find the time, to (re)set priorities, and maintain focus on our values; moving from known to unknown. For my bench research, this meant careful study of chemistry, immunology and biomaterials...before we could move into uncharted territory like injectable biomaterials for transplant tolerance. Reconstruction of traumatic, oncologic or congenital issues necessitates a deep understanding of the pathophysiology before making a decision on what could be done next. To push the boundaries of human knowledge, it requires risk-taking, but in surgery, these must be calculated risks. It is my belief that with dedicated practice in the surgical arts, supported by mentors and sponsors, inspired by role models along the way, we can move with confidence from known to unknown. The unknown can be intimidating – but when supported by solid evidence, experience, and inference, together we can do hard things.

About the AWS Research Fellowship
For more than 25 years, the Association of Women Surgeons has supported surgeon scientists advance and develop their careers through grant funding. AWS will offer one grant for clinical/education research. Dr. Holly Lewis was the 2023 AWS Research Fellow.