ASTCT asked Shernan Holtan, MD questions about what it is like to be a woman in the transplantation and cellular therapy field in celebration of Women's History Month, March 2022.

What inspired you to enter the BMT and Cellular Therapy field?

I became inspired by the field as a University of Nebraska medical student seeing graft-versus-host disease during my dermatology rotation. How incredible to think that receiving another person’s immune system could cure leukemia? I was instantly fascinated. I requested an elective BMT rotation with Dr. Steven Pavletic and loved every minute of it. When I started my internship at Mayo Clinic, Dr. Angela Dispenzieri was fortuitously assigned as my advisor. I told her my clinical interests were hematology, rheumatology, and infections diseases. She called it instantly, “You are going to be a transplanter.”

How do you inspire others?

I tend to share a lot about my various non-medical passions both in person and on social media, making boundaries between my work and personal life sometimes blur. For example, I often post about strength training, both the personal work I am doing as well as research from my collaborators and others. I hope my posts encourage others to experience the joy of strength training. At the last in-person TCT meetings, I had an attendee rush up to me and gleefully exclaim, “I follow you on Twitter and just have to share that I recently hit a personal record in the squat!” Huge smiles and high fives all around!

Which living person do you most admire?

I most admire my father. He is a cabinet maker in rural Nebraska. He loves nothing more than “making sawdust.” In his mid-30s, he suddenly became paralyzed from the waist down after a fulminant episode of transverse myelitis in the context of other HLA-B27-related inflammatory problems. Despite multiple ongoing health-related battles, he is still here 30 years later. He demonstrates a high level of medical self-efficacy, paying careful attention to his diet, exercise, sleep, and reading primary scientific literature when he has a clinical concern. Most importantly, he wakes up every day with a sense of purpose and joy, focusing on doing creative work that he loves. My dad sets the best example of how to live a good, meaningful life.

What does it mean to you to be a woman in this field?

The BMT and Cellular Therapy field, and the University of Minnesota in particular, has an incredible legacy of female leadership. I feel a sense of honor to be walking the same halls as Norma Ramsey, Clara Bloomfield, Lisa Filipovich, Stella Davies, Linda Burns, Margaret MacMillan, and many other trailblazing women. Nonetheless, challenges for female faculty remain, and I feel compelled to try to make the path smoother for others. As a field, we have to recognize female faculty loss at mid- and late-career stages. I recently reviewed the first/last author data on the top 200 cited manuscripts for acute GVHD. While 28% of the manuscripts have female first authors, only ~10% have female senior authors. See my tweetorial about this “impact gap” in female-led acute GVHD research. We have work to do.

What do you consider your greatest achievement?

I am most proud of the 12+ year journey from conception (of an idea!) through to obtaining FDA orphan drug designation for urinary-derived human chorionic gonadotropin for life-threatening acute GVHD.  We are reporting our phase II study results at this year’s TCT meetings. We completed all the work without funding from the pharmaceutical industry. Our data will never get the same hype as an industry-funded study, so the results will have to speak for themselves. It has been so gratifying to see an inexpensive, readily available drug help improve people’s lives. The kid who first gave me this idea is now in high school.

Who are your heroes in real life?

Dr. Svetomir Markovic, my primary mentor throughout residency and fellowship, continues to inspire me through his ability to translate devastating problems in the clinic into experiments in the lab, which in turn lead to investigator-led clinical trials. He once told me that he remembers conversations from all of the patients who have cryovials of cells stored in his lab. Having conducted my own hard-earned phase I/II study, I now completely understand what he means. Dr. Angela Panoskaltsis-Mortari is a phenomenal scientist, leader of multiple labs and core facilities at UMN, mentor, mother, cook, and dancer. This woman can do anything with grace!  Dr. Daniel Weisdorf is also an academic hero for me. He has an amazing ability to see the real story through messy data. He has always encouraged me to think bigger and take more chances than I would have otherwise been inclined to. I wouldn’t be where I am today without him.

Is there anything else you would like to say to the ASTCT community?

I’d like to recognize 2 female BMT faculty who have provided me with a great deal of support and inspiration for the past 10+ years. Dr. Alla Keyzner of Mount Sinai is a friend and personal hero. She was my co-BMT fellow at Mayo Clinic, and she is one of the best BMT docs and clinical researchers around. Our kids were born just 2 weeks apart, and we will always have a special connection because of that. I have enjoyed watching her career grow, and if I ever personally need a transplant, she’d be the first woman I would call.  Dr. Laura Newell is a basic/translational scientist at Oregon Health and Science University and true disciple of Dr. Eli Estey. She is also the most detail-oriented person I know. She is the “splitter” to my “lumper,” and we provide excellent counterbalance for each other. I’m grateful for her ongoing friendship and collaboration. We have so much fun working together, it makes the drudgery worthwhile.

About Shernan Holtan, MD:

Shernan is an Associate Professor of Medicine, co-leader of the Graft-Versus-Host Disease (GVHD) interdisciplinary team for the Masonic Cancer Center, and clinical/translational investigator.  Her research focuses on developing and testing biomarkers for acute GVHD, the major complication of HCT, as well as designing non/minimally-immunosuppressive supportive therapies. She has approached the problem of acute GVHD from the goal of enhancing normal tissue repair and microbial/immune homeostasis, rather than intensification of immune suppression, in patients with high-risk or steroid-refractory disease. Her ongoing, grant-funded clinical/translational studies include identification of novel tissue repair growth factors and pathways associated with prognosis in GVHD and development of longitudinal monitoring biomarkers (amphiregulin) that has been validated in samples from prospective multicenter studies. Her gene expression studies of rectosigmoid biopsies of patients with fatal GVHD point to DNA damage, senescence, and stress responses as underlying the lack of response to standard immunosuppression. She is the principal investigator on several investigator-initiated clinical trials, and she is protocol co-chair on the BMT CTN 1703 phase III study comparing tacrolimus/methotrexate to post-transplant cyclophosphamide/tacrolimus/MMF.

Tags: transplantation, Womens History Month, Cellular therapy, cell therapy, 2022, Women, woman, history, month, womens history, march