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In View: People in Transplantation

Ginny L. Bumgardner, MD, PhD

Bumgardner, Ginny L. MD, PhD

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doi: 10.1097/TP.0000000000001893
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Transplantation: You are one of the few surgeon/scientists in transplantation. What motivated you to get into surgery and transplantation? What excites you about being an academic surgeon?

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GB: There are some transitions that are so memorable one never forgets them. I started medical school at the University of Virginia early by taking advantage of a summer rotation in rural Virginia thinking I wanted to be a family practitioner. Then I encountered Immunology during my first 2 years of medical school and absolutely loved learning everything there was to know about the field. It was definitely my third-year medical student rotation when I met so many talented general surgery residents, experienced the excitement of the operating room, and saw the clinical impact of transplantation that I knew for sure I wanted to train to become a transplant surgeon. Dr. Wallace Ritchie was an important mentor who helped me identify the University of Minnesota as a General Surgery training program which was not only recognized as a world-renowned Transplantation Center but also offered an NIH-funded training grant entitled “Surgery & Immunology.” It was a perfect fit, and I was fortunate to be accepted into the program. Little did I know that the training I received there and the people I met would forever impact my life and career. The Transplant Experience at the University of Minnesota was remarkable and instilled a lifelong commitment to a career in academic surgery where one is privileged to care for complex patients, identify and pursue important research questions that derive from one’s clinical experience and work with students, staff and colleagues who collaborate to create this wonderfully engaging and exciting learning environment.

Transplantation: You have an active, NIH funded research laboratory. How do you develop concepts and ideas for the laboratory?

GB: We start with identifying questions that are of clinical importance and have a potential significant impact to transplant patients. The research questions are informed by clinical experience, networking at scientific meetings, reading the literature, conversations with colleagues and other researchers. Of course members of the research team are a great source of new ideas and directions which then lead us to recruit collaborators with specific expertise to help us pursue these ideas.

Transplantation: You have identified suppressor effects of CD-8+ T cells, a population that we traditionally link to cytotoxic effects. What characterizes those cells and what is their clinical relevance?

GB: As much as I initially hesitated to call this novel subset “CD8+ antibody suppressor T cells” that is what they do and at least part of their actions are mediated by cytotoxic effects on alloprimed B cells. These cells appear to develop endogenously in response to immunogenic stimuli and downregulate humoral immune responses not only to alloantigens but also to other antigens as well. In experimental models these cells are IFNγ+CD8+ T cells, and we are currently preparing a manuscript that will report on approaches for enriching these cells. We have collected some exciting clinical data which support the activity of CD8+ antibody suppressor T cells in humans. In this ongoing prospective study, we found that kidney transplant patients who develop donor-specific antibody (DSA) have significantly lower frequencies of IFNγ+CD8+ T cells than the patients who remain DSA negative.

Transplantation: You have also shown a link between the suppressive effects of CD-8 T cells and antibody responses. What is the potential impact of those findings?

GB: It is well established that alloantibodies cause both acute antibody mediated rejection and negatively impact long-term allograft survival across the spectrum of cell and organ transplantation. The downregulation of alloantibody production by CD8+ antibody suppressor T cells is therefore beneficial to transplant recipients. These CD8+ T cells exert antigen-specific cytotoxic effects on alloprimed B cells and may also exert noncytotoxic cytokine-mediated effects on other immune cell subsets. In transplantation, we commonly use induction as well as maintenance immunosuppression. We need to remember that when we deplete all T cells, this includes both deleterious alloreactive cells but also alloreactive cells that are beneficial. Conventional immunosuppressive agents, such as CNi and mTORi, both suppress T cells that mediate rejection, however, they do not exert similar effects on CD8+ antibody suppressor T cells. While CNi suppresses CD8+ T Ab-Supp activity, mTORi does not.1

These studies illustrate the multilayered effects of immunosuppression and the importance of comprehensively examining the impact of immunotherapies in transplant patients.

Transplantation: Beyond your clinical and research activities, you are training and educating medical students and residents. What do you consider key in motivating the future generation in transplantation?

GB: Medical students and residents these days are talented in so many different ways. It is essential for our field to recruit the best and the brightest workforce of the future. I think the key to motivating medical students and residents to pursue a challenging field like surgery and a surgeon-scientist career path is first to convey one’s own passion about the importance and fulfillment of our work. It is also critical to equip them with the tools and build confidence that they are fully capable and needed to improve the surgical care of the future while creating opportunities to recognize and reward their high-level achievement.

Transplantation: How would you advise medical students or young clinicians with an interest in transplantation? Would you have a special advice for females with an interest in our field?

GB: I would advise students potentially interested in transplantation to get involved early! They should spend some time with the transplant team, pursue transplanted related research where they can work closely with a transplant mentor, read the transplant literature, apply for medical student/resident fellowships or travel awards which support transplant research and attendance at Transplant meetings. Finding mentors early on who can talk to students about their interests, passions and reservations is important for both, female and male students and young clinicians.

Transplantation: You have developed a professional Development Program at your Institution. What defines leadership and how do you teach to lead?

GB: Our professional development program is designed to support the development of our surgery residents as future leaders in surgery. When I use the word “leader” I do not necessarily mean surgeons with titles or with administrative positions. Instead, I mean a surgeon who has the vision, passion, commitment, and skills to meaningful impact surgical care, surgical education or research relevant to surgical patients through the creation of new knowledge, new paradigms, new approaches, new treatments and/or new tools. Whether our residents choose academic surgery or private practice, we support their confidence and preparedness to lead innovation, lead programmatic improvements, lead collaborative solutions, lead research teams and projects and to disseminate important results through national presentations and peer-reviewed publications. We facilitate these goals through integration of their clinical and research training and professional development experiences. First, they must work hard to develop clinical expertise in surgery because it is this critical eye and attention to detail that motivates the passion to work for improvement. The training in research provides them with skills to identify important questions and gaps in the field and to design research and action plans to solve the problem they identify. We emphasize science communication as part of their professional development—both as written and oral communication. Our residents gain substantial experience with publishing manuscripts, submitting grant applications, and presenting results of their research at national and international meetings. People who gravitate to surgery are action oriented by nature and our professional development program widens their perspectives and broadens the scope of their abilities to impact the field of surgery. We do this by personalizing their research experience, pairing them with dedicated faculty mentors, offering didactics on topics not typically part of a surgery residency curriculum, creating opportunities to meet not only with senior faculty in the Department of Surgery but also with leaders throughout the College of Medicine and the Ohio State University. We support their intellectual discourse at scientific conferences, identify national networking opportunities and recognize achievement.

Transplantation: You have received an NIH training grant supporting ‘Advanced research Training in Immunology for Surgical Trainees. How do you use this approach in advancing skills and research interests of residents?

GB: It is critically important to train a cadre of surgeons to pursue research that is relevant to surgical patients. Immunology has broad applications to surgical problems. Consequently, our trainees are poised to pursue research in Immunology relevant to a variety of surgical specialties. The award of this training grant has enhanced our research training program in many ways. First, the grant attracts the type of surgical trainees we want to train—those who understand the importance of Immunology Research and who foresee an academic surgical career. This grant provides expanded mentorship opportunities for residents in our program and has catalyzed new multidisciplinary collaborations as well as the development of new courses and other more informal educational experiences. When our residents complete their research training they are confident in research design, application of biostatistics to research questions, preparation of manuscripts for publication, oral and poster presentation of their work, and have hands-on experience with grant applications.

Transplantation: How do you manage having a triple career as an educator, surgeon and scientist?

GB: While these roles may appear to be separate, I view them as interrelated and linked to one another. My role as an educator focuses on surgery, immunology, research education and career development for physician-scientists. My clinical and experimental research questions are immunology-focused and related to my clinical practice in transplantation. My students are interested in surgery and transplant immunology.

Transplantation: What are your interests outside of your professional career and how do you balance private and professional interests?

GB: I like spending time with family and friends, and I like to cook gourmet dinners for them. I admire American arts and crafts and am a faithful patron of arts festivals. I enjoy quiet time to read great fiction, the New York Times, and arts-themed magazines. My children keep my husband and me really busy. We like to travel. My children have taken piano lessons for more than 8 to 9 years, and their skills encouraged me to take lessons too. Balancing personal and professional interests is a dynamic process which my husband and I are continually juggling to make work. Sometimes new hobbies replace old ones. I enjoy horseback riding but this is a very time-consuming hobby and while my husband and I once had 7 horses and showed our horses, we no longer stable or ride horses. More recently, I have taken piano lessons once a week and take part in other activities which do not require as much time.

REFERENCE

1. Avila CL, Zimmerer JM, Elzein SM, et al. mTOR inhibition suppresses posttransplant alloantibody production through direct inhibition of alloprimed B Cells and sparing of CD8+ antibody-suppressing T cells. Transplantation. 2016;100:1898–1906.
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