Myeloma expert Sarah A. Holstein, MD, PhD, was born and reared in Iowa City, a college town in eastern Iowa along the banks of the Iowa River. “The town itself is small, but it doubles in population when all the college students are present. Both my parents had a PhD in humanities, so I had no exposure to medicine at a professional level,” she shared.
Asked what drove her interest in medicine, Dr. Holstein replied: “I was always a good student and enjoyed all my classes. But going into high school, I began to have an interest in math and chemistry classes. However, during my senior year in high school, when I had to give serious thought to what I wanted to study in college, I was torn between two choices: pursuing a career in music or science. I was a serious flute player, which was where a lot of my time and passion was spent during high school. But I ultimately decided to major in chemistry.”
Sarah A. Holstein, MD, PhD
Staying Near Home
Dr. Holstein remained at home in Iowa City to do her undergraduate work at the University of Iowa (UI), where she majored in chemistry. “Everything was going along as planned, but then during my junior year at UI, I received an opportunity to work in a chemistry lab, which was my first experience with scientific research, and I fell in love with it. It fit my personality as an introvert and someone who was detail-oriented and passionate about discovering new things. Those 2 years in undergrad, when I spent almost all my free time in the lab, solidified my latent desire to pursue scientific research as a career,” she said. She added “the laboratory I worked in was led by David F. Wiemer, PhD and not only did he have a significant influence on the trajectory of my career, he remains my closest scientific collaborator.”
Dr. Holstein continued: “Someone suggested to me when I was an undergrad the possibility of pursuing a dual MD/PhD degree. I must admit I did not know anything about medical school or the career of medicine, for that matter. But the thought of pursing something that would eventually lead me to a career in research that could have a positive downstream impact on disease and human health was extremely appealing. However, I was certainly naive about medicine as a career.
Entering Medical School: Big Decisions Ahead
Prior to beginning medical school, Dr. Holstein did another research rotation in the laboratory of Raymond Hohl, MD, PhD. “Dr. Hohl played an enormous role as a mentor, which accelerated my research career. In his lab is where I first had the opportunity to do cell-based research that was focused on how drugs work, particularly in cancer cells. I found that work so interesting that I decided I didn’t want to go back to the organic chemistry world for my PhD; I wanted to do more cancer-related research.”
In 2000, Dr. Holstein entered the Medical Scientist Training Program at the University of Iowa Carver College of Medicine, still unsure of the specialty she wanted to pursue. “I did the the first 2 years of medical school classes and then did a rotation in internal medicine the summer before transitioning into my PhD studies. The internal medicine rotation was important because it was the first time that I got to spend any significant time on an inpatient unit, where I truly saw what medicine was all about. By then, I’d pretty much figured out that I didn’t want to spend my time in an operating room, and my internal medicine rotation was a very positive clinical experience; I got to see all the many working parts of diagnosis and treatment as well as various problem-solving techniques,” she related.
Following her internal medicine rotation, Dr. Holstein began her PhD studies, largely focusing on cancer-based projects. “I worked on some very interesting projects, such as trying to discover how novel small drugs worked and trying to understand the implications of disrupting different pathways in cancer cells. During that period, I learned more about Dr. Hohl’s life as a physician-scientist. I spent some valuable time shadowing him, seeing what types of patients he saw in his oncology practice. That, coupled with the research interest in cancer, got me seriously thinking about oncology,” she explained.
Deciding on a Career Path
Toward the end of her PhD training, Dr. Holstein had to decide whether to pursue a traditional internal medicine residency followed by a traditional hematology/oncology fellowship or pursue a special program for students like her who had done MD/PhD training. “The program, called a PSTP (physician scientist training program), is designed to help make the transition from residency to fellowship and into academia. My long-term goals were based on modeling myself after my mentors, in other words being an oncologist who runs a laboratory as well. So, I decided to remain at the University of Iowa to pursue the PSTP training,” she recalled.
Dr. Holstein continued: “Just to backtrack, during my internal medicine residency, I was able to spend time on the hematology/oncology inpatient service. At that time, the service was run by house staff, and patients with acute leukemia were treated on that service; I truly got a global picture of the specialty, from making the initial diagnosis, to starting patients on treatment, to seeing the complications that can arise from chemotherapy. It was right at the time when novel agents such as imatinib, erlotinib, and bevacizumab were first being used. So, it was a great learning experience that also accelerated my passion for oncology. Plus, it dovetailed with my PhD, which was in pharmacology.”
In 2006, having decided to pursue oncology, Dr. Holstein entered a 4-year hematology/oncology fellowship at the University of Iowa. “For the first 18 months, I just did clinical rotations, and the following 2 and a half years, I went back to the lab to work on a project that would lead to my independent researcher status. Throughout my fellowship, I was also working in Dr. Hohl’s clinic, which had a lot of patients with multiple myeloma, and it was around the time when lenalidomide was first being used. In fact, I think the first time I met a patient on lenalidomide was before it had been [U.S. Food and Drug Administration]-approved, and they were receiving it on a clinical trial. Even during the relatively brief period of my fellowship, I saw first-hand the remarkable results that more effective therapies (such as lenalidomide and bortezomib) could have compared to some of the traditional cytotoxic agents that were previously being used. I felt like I had a front-row seat to watch how bench-to-bedside research could transform patient outcomes for the better. This was a significant reason I decided to become a multiple myeloma specialist and devote my research career to the disease as well,” she said.
A Chance to Develop Her Own Program
After completing her fellowship, Dr. Holstein stayed on at the University of Iowa, serving as a myeloma specialist and establishing her independent laboratory program. She subsequently accepted a position at Roswell Park Comprehensive Cancer Center. “Roswell was great from a clinical perspective, which helped broaden my clinical research career objectives. But then an opportunity arose at the University of Nebraska Medical Center [UNMC] to develop my own myeloma program, which I jumped at; I have been here for over 6 years and never regretted that decision. It’s busy for sure, and I wear a lot of hats. Even during days when I’m in the clinic seeing patients with plasma cell disorders, I still do lab work either before or after the clinic. I also have research days, but there is never a clean divide between the lab and the clinic. There are always manuscripts and grants to write, journal editorial work to do, trials to design, administrative work, and mentoring. It’s a constant struggle to keep everything afloat, but UNMC is a great supportive place to work.”
Dr. Holstein shared these concluding remarks: “Oncology is a very emotionally challenging field, but it is also incredibly rewarding, especially when you see the work done in the lab transition to improved outcomes for patients. For me, multiple myeloma has now turned into a cancer where I can, again because of the advances we’ve seen, develop longer-term relationships with my patients. So, being in academics, it gives me the opportunity to be a part of this incredible progress on the ground level, from bench to bedside. The goal of my research is to develop novel small molecules that disrupt intracellular trafficking in cancer cells—a strategy that we have found to be particularly effective in cancer types characterized by abnormal protein production/secretion, including multiple myeloma and pancreatic cancer.”
What does a super-busy oncology leader do to decompress? “I still love playing the flute and am grateful to have been able to play with the Nebraska Medical Orchestra prior to the COVID-19 pandemic. My husband and I share our home with four dogs and a cat, all rescues we have adopted since moving to Nebraska. I’ve been working on my baking skills and expanding my garden. That’s pretty much all I need to center myself from work.”
DISCLOSURE: Dr. Holstein has served as a consultant for or received honoraria from BMS/Celgene, Genentech, GSK, Janssen, Oncopeptides, Sanofi, SecuraBio, and Takeda and has received research funding from BMS/Celgene and Oncopeptides.
Dr. Holstein is Professor in the Department of Internal Medicine, Division of Oncology & Hematology, University of Nebraska Medical Center, Omaha.