Roslyn (“Roz”) Bernstein Mannon, MD : Transplantation

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In View: People in Transplantation

Roslyn (“Roz”) Bernstein Mannon, MD

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Transplantation 106(1):p 6-8, January 2022. | DOI: 10.1097/TP.0000000000003944
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You grew up in Manhattan, went to Johns Hopkins for your undergraduate studies, and then went to Duke for Medical School and were on faculty there. What motivated you to go into transplantation?

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RM: During our first month of medical school, a Clinical Pathology Conference was held on kidney disease, and the participant was a young man who had end-stage kidney disease, presented by the transplant surgeon, Dr Randy Bollinger. The patient talked about being on dialysis and showed us his enormous arteriovenous fistula. He went on describing how his life had been changed dramatically for the better after his renal transplant, allowing him to work and take care of his family. During my second-year clinical rotation, Dr Sabiston, the chair of surgery at Duke, asked each student if we had an area of interest in surgery. When I said transplantation, I was given a pager and was on call with the kidney transplant team for 3 wk. I scrubbed in and assisted on about 6 transplants, almost all live donors. Dr Bollinger enjoyed showing the rapid return of blood flow and function after the clamps came off and the anastomoses were complete. He was gleeful when urine streamed across the operative table. I remember that experience vividly, and, needless to say, I was hooked (and got honors on my surgery rotation). The rest, as they say, is history. I did my fellowship research in Tom Coffman’s laboratory. My collaborators included Fred Sanfilippo, Wink Baldwin (who walked me through using the flow cytometer), Phil Ruiz, and Jeff Platt. I finally got my K08 funded, focusing on basic immunological aspects of T-cell development and rejection, and worked as the medical director for kidney transplantation at the Durham Veterans Administration Hospital.

After your faculty appointment at Duke, you moved to the National Institutes of Health where you became the Medical Director of Transplantation. What were experiences and achievements in this unique environment that combined clinical and research work?

RM: The transplant program at the National Institutes of Health (NIH) was created by the National Institute of Diabetes and Digestive and Kidney Diseases as part of the intramural research program. A United Network for Organ Sharing–certified kidney and kidney/pancreas program was formed, with Allan Kirk as surgical director and me as medical director. We had a second transplant surgeon on site, Doug Hale, with additional support from S. John Swanson and D. Scott Batty, both Walter Reed Army surgeons. Our pathologist was David Kleiner, who specialized in liver injury but spent time learning Banff criteria; the HLA laboratory was located at Walter Reed. Nursing and coordinator staff were recruited and trained, all focusing on novel approaches to transplantation, very much like a giant, immersive clinical research center. Our laboratories were initially at Bethesda Naval Hospital, but after 9/11, we were moved back to NIH main campus. Allan’s experimental models focused on primates, and mine focused on mouse transplants. Allan and Doug concentrated their work on acute rejection and tolerance, which complemented my interest in late allograft failure. With the relatively small size of the program (~50 patients a y), all patients were on protocols that included novel agents such as anti-CD40 ligand, alemtuzumab, and high-dose rabbit anti-thymocyte globulin, as well as bone marrow transplantation. We had biomarkers and mechanistic studies embedded in all of our trials. All of us also provided clinical support for the islet transplant program (David Harlan was Primary Investigator). This experience really gave me my skills in clinical and translational research because we were literally a bench-to-bedside-to-bench team.

After spending time at the University of Alabama at Birmingham as Section Chief for Transplant Nephrology, Director of Research, and Robin Luke Professor of Nephrology, you have recently moved to the Nebraska Medical Center as Professor of Medicine, Pathology, and Microbiology. What are your goals at your new institution?

RM: My most recent prepandemic move was triggered by a fantastic academic opportunity for my spouse, Peter, who dutifully moved with me to the NIH and to the University of Alabama in support of my academic development. As Vice Chair of Academic Development for the Department of Medicine, I have an opportunity to apply my leadership and mentorship skills at a departmental level. With my recruitment, we are focusing programs and support to ensure that faculty continue to grow in their career advancement along all promotional levels. Our department has already enacted efforts, but those are primarily focused on junior faculty in addition to clinically focused activities. My goals are to provide more transparency about promotion and tenure but also define opportunities and help faculty at all levels to advance. I also serve as a codirector of our Medical Scholars Program, a graduate studies program. Finally, I am working to raise the level of investigation in nephrology through both basic and clinical research programs, identifying collaborators for the division and ultimately including bench scientists in our division. The Nebraska Medical Center has an outstanding Department of Cellular and Integrative Physiology. For transplantation, our program is medium-sized with great clinical outcomes, providing opportunities for NIH-funded studies such as the Clinical Trials in Organ Transplantation. I have been very involved in the consortium since working with Chris Larsen back in 2008 and other innovators including Flavio Vincenti. My clinical goals include working with the living donor program to expand its volume and continuing my Veterans Administration Hospital service record by rounding on general nephrology at the Nebraska Western Iowa Health System. I am very much looking forward to those exciting perspectives!

You have taught many who went on to have their independent research and clinical careers. What is your “mentoring secret”?

RM: I think it is important to be honest with your mentee and to establish clear goals at the start of the relationship. Is this a short-term or project-specific relationship? Or is this for the long term? For any relationship, it is important for the mentee to distinctly create a mutually agreeable timeline. It is also important to realize that some mentees may have multiple mentors and that you should be confident that this is a good thing, unless you believe it is interfering with their development to becoming independent. It is also very important as a mentor to allow someone to flourish and to grow, aiming for an independent research career. I also believe that a good mentor provides sponsorship and networking opportunities. I really miss poster sessions at our meetings where you can meet up with a mentee, grab a drink, walk posters, and introduce them to people you know, facilitating name recognition and perhaps identifying new collaborators.

One of your research interests has been on late graft dysfunction. What recent strides have been made to address this so important phenomenon?

RM: More than 10 y ago, when I moved to University of Alabama at Birmingham, I became part of the long-term Deterioration of Kidney Allograft Function Consortium, an NIH-funded study that created a large observational registry of those with late graft failure with an additional prospective cohort focusing on those developing chronic graft failure. Coupled with my preclinical rodent study experiences, this was a unique opportunity for me, working with some of the key leaders in kidney transplantation, pathology, and HLA antibody testing. These studies led to several key clinical findings, including defining the contribution of antidonor antibodies to kidney graft failure and the notion that scared areas of the kidney and the inflammation in them had relevance to graft failure and not just representing “remodeling.” These studies have led to multiple new contributions including risk modeling and more detailed understanding of antibody-medicated injury and nonadherence. It is clear that antibody plays a role and hence the monitoring of such donor-specific antibody is tacit to patient management. Finally, our understanding of genomics and disparities between donors and recipients (be it HLA and non-HLA proteins) is having an impact. Whether this will lead to new biomarkers, treatments, or new allocations schemes remains to be seen.

One reason for not doing better in addressing chronic allograft vasculopathy is the absence of reliable biomarkers. Where do you see progress?

RM: HLA donor-specific antibodies provide one potential biomarker. Recent genomics investigations by several groups, be it in peripheral blood or allograft biopsies, are promising and will require clinical validation. There are studies, including those from my own group, focusing on fibrosis markers, but again, the limitation here is that fibrosis is the final common pathway of many different injuries. I think the bigger questions relate to optimizing therapies. We do not have effective treatments for late antibody-mediated rejection, whether acute or chronic active. Likewise, we have an expanding comprehension of the complexity of the immune response, including potential contributions of innate mechanisms, but have been unable to confirm effective treatments. Thus, even more important than a test to detect a graft “on the skids,” we need effective treatments as we continue to identify novel and important mechanistic pathways.

Although we have made progress in understanding the biology of alloimmunity, we have not been able to get novel immunosuppressants positioned in the clinic. It is 10 y back that the last new immunosuppressants have been approved by the US Food and Drug Administration. What are obstacles and potential solutions?

RM: With belatacept as the last new investigational agent approved for transplantation, I was committed to making an impact and inspired by others like Flavio Vincenti and Randy Morris. During my American Society of Transplantation presidency, I dedicated my efforts to lobby the US Food and Drug Administration to do more for transplantation with the goal of creating a private–public partnership focusing on transplant therapeutics (and devices). I drafted a white paper on this topic with Flavio, Tim Schroeder, and Rita Alloway to get that initial message across about the things that needed to change (https://www.myast.org/sites/default/files/pdfs/fda_moucalltoaction_final_5_13_13.pdf). It took about 4 y to make headway until the Transplant Therapeutics Consortium was forged as a private–public partnership with the Critical Path Institute, on which I currently serve as The Transplantation Society representative. This organization focuses on defining surrogate endpoints for outcomes in kidney transplantation. We are also amassing a very large standardized database for kidney transplantation under the Transplant Therapeutics Consortium, documenting multiple study subjects over the last 2 decades to assist with modeling of outcomes.

As past President of the American Society of Transplantation and now as Chair of the Women in Transplantation initiative, you have been and continue to be in key positions to address disparities in the representation of female transplant professionals. What are measures that can be implemented?

RM: Recently, in light of the murder of George Floyd and Black Lives Matter movement, many organizations have finally begun to focus on diversity/equity/inclusion and such recognition includes formalized training and participation in many levels of the academic enterprise. Even in the United States, we have dramatic disparities in academic development in women as well as individuals of color, as noted in the recently published Association of American Medical Colleges State of Women in Academic Medicine 2018–2019 report. The pipeline from instructor to full professor and finally leadership positions has failed to have women reaching those more senior ranks. A key focus is education. There is a lot of literature showing these disparities and leveraging such data to see what kinds of support and programs are needed to help women faculty bridge to higher levels. Coronavirus disease 2019 has certainly exacerbated those issues as well. At Women in Transplantation, we address this through 3 avenues: networking (pillar 1), research (pillar 2), and advocacy (pillar 3). We aim to have women participants equally at national and international meetings; we expect to have women considered for leadership awards from the societies and represented fairly on editorial boards, on the leadership of those boards, and on societal council rosters, as many examples. We actively collaborate with various societies across the globe and communicate this message, as the disparities seen in North America are even more profound in Asia and Africa. The process for diversity/equity/inclusion has to be an active thought process rather than an “afterthought.”

Where do you see research initiatives that can be moved forward to address gender and sex disparities?

RM: Recognition of this issue by anyone performing research is critical to moving forward. This is clearly registering with the NIH and other funding agencies and now with medical journals. While there has already been recognition of the impact of sex differences in cardiovascular disease or metabolic issues, recent studies now recognize the potential differences in immunological profiles in sex and aging. It is a challenge now to replicate prior work in both sexes. It is obvious that additional funding will be needed to support this research avenue. Two additional important research goals are of relevance: to develop a more robust understanding of the impact of sex on transplant outcomes and transplant immunology and to develop expertise in this space, which is lacking because many Primary Investigators are new to this area of investigation. Hence, as Women in Transplantation Chair, I have been working with Industry to establish fellowship grant awards to develop careers in sex and gender in transplantation. We started with two 2-y awards this past summer and hope to grow this research program.

A lot of your time is certainly absorbed by professional responsibilities. What do you do to recharge?

RM: As a working mom, there is never enough “free time.” I am an enthusiastic fan of both college football (Roll Tide) and college basketball (Go Devils). Both my daughters are athletes, playing multiple sports, including soccer, track, and basketball. By growing up in Maryland, they learned to play lacrosse in grade school and were both collegiate players, Ellie at Wellesley College and Olivia at Fresno State and the University of Oregon. So, I became a lacrosse mom for a good number of years, traveling all over the United States for tournaments with their competitive club teams and for collegiate matches. Olivia also played on the Israel National Team in 2019 (pre–coronavirus disease 2019), when the team won a silver medal in the Euros. I have 2 Spinone Italianos, Paolo and Luca, so I am a busy dog mom. I have been a volunteer in my congregation. Finally, I enjoy reading novels (especially science fiction), needlework (I never seem to finish my projects…), traveling (for fun, not work…), and eating—my spouse is an amazing cook!

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