The Cancer Genome Atlas remains a very successful project and during those early years we were able to learn a lot about infrastructure needs, bio-banking and bioinformatics. It certainly had a stimulatory effect on technology, advancing next-generation sequencing technologies which continue to give us a deeper knowledge of cancer genomics.
—John E. Niederhuber, MD
John E. Niederhuber, MD, was born and grew up in Steubenville, Ohio, a steel mill town located along the Ohio River. Dr. Niederhuber had a childhood interest in engineering and chemistry, but it was the town’s general practitioner who made a lasting impact on his career path. “He was an old-style family doctor. He did everything from setting a broken bone to delivering babies. If one of us was sick, he’d just say, ‘OK, I’ll stop by on my way home.’ He was an early influence on my decision to pursue a medical career,” said Dr. Niederhuber.
After high school, Dr. Niederhuber attended Bethany College, a small liberal arts college in West Virginia. “I was one of only eight chemistry majors at Bethany and in my senior year I was given the opportunity to design my own research project. The work actually led to a National Science Foundation grant,” said Dr. Niederhuber.
It was while running his own research project at Bethany that Dr. Niederhuber decided to go to medical school. “Our family had limited resources, so I was delighted when I was accepted to Ohio State University School of Medicine, which, being a state school was relatively inexpensive. I decided to get my medical degree and then figure out how to go to graduate school and pursue my interest in biomedical research,” said Dr. Niederhuber.
From Orderly to Surgeon
During the summer before his first year at Ohio State, Dr. Niederhuber got a job as an orderly in the operating room of a local community hospital in Columbus, Ohio, bringing patients to the operating room and cleaning up after surgery. By the end of the summer, Dr. Niederhuber’s responsibilities had expanded to among other tasks, working as a scrub technician. Working weekends and occasional nights in the operating room helped support Dr. Niederhuber throughout medical school.
This experience also influenced Dr. Niederhuber’s decision to become a surgeon. He recalled one particular Saturday afternoon that first summer working as an orderly in the operating room when his interest in surgery was put to a serendipitous test. “A young man came into the operating room with an open ankle fracture. The attending surgeon mistook me for a hospital intern. He asked if I wanted to scrub and assist. The nurse looked at me and winked, so I scrubbed and assisted in the operation. I actually placed a couple of surgical screws into the bone and helped close the incision. Years afterward, I ran into that surgeon who had later realized that I was only a student at the time I assisted him. We had a good laugh about it,” said Dr. Niederhuber.
A Mentor’s Influence
Between his junior and senior years in medical school, Dr. Niederhuber worked in the Laboratory of Robert M. Zollinger, MD, Chairman of Surgery at Ohio State University.
“Dr. Zollinger directed an elaborate research program studying gastric physiology and especially the role of gastrin. He had a large colony of beagle dogs and the projects required my doing gastric surgery creating different kinds of gastric pouches. I operated on these dogs every day so by the time I graduated from medical school, the technical aspects of performing abdominal surgery had become second nature,” said Dr. Niederhuber. He credits Dr. Zollinger as a valued mentor. “He taught me a lot about surgery, but he also helped me develop better patient care skills. His attention to detail regarding each patient was unmatched in my experience. I maintained a close relationship with Dr. Zollinger throughout my career,” said Dr. Niederhuber.
After receiving his medical degree from Ohio State, Dr. Niederhuber stayed on at the university for his first year of surgical residency. During that first year, he applied to graduate school, planning to pursue a PhD. However, it was 1967, and the escalating war in Vietnam put his plans on hold. Dr. Niederhuber was drafted into the Army. “I did my 2-year tour of duty at Fort Detrick in Frederick, Maryland, which was home to the U.S. Army’s Center for Biological Research focused on infectious agents. After that I went to the University of Michigan, enticed by a very attractive scientific research program,” said Dr. Niederhuber.
Best of Both Worlds
Dr. Niederhuber’s decision to attend the University of Michigan was largely influenced by another valued mentor, C. Gardner Child, MD, the university’s Chair of Surgery, who ensured Dr. Niederhuber that he would have a robust research experience during his surgical training. “Dr. Child came through on his promise. The university sponsored me as a visiting fellow in the division of immunology at The Karolinska Institute in Stockholm, Sweden. These were the early days of being able to isolate T-cells and B-cells from mouse tissues and to use these cells in vitro to model antibody response to antigens. The immunology environment in Sweden and Europe was electric in those years and the laboratory, headed by Göran and Erna Möller, had a steady stream of visiting immunology stars,” Dr. Niederhuber related.
After completing his fellowship, Dr. Niederhuber returned to the University of Michigan to finish his surgical training and to consider his career direction. That’s when Dr. Child intervened again. “He had gone to the Chairman of the Department of Microbiology at the university and worked out an arrangement that gave me a full faculty appointment as an Assistant Professor in Microbiology and a full appointment as Assistant Professor of Surgery. Further, they arranged for my research laboratory to be located in the Department of Microbiology. I was to teach at the graduate level and was approved to train doctoral students. This combined experience, working in a basic science department and in a clinical department, gave me the fantastic opportunity to grow up professionally on both sides of the medical campus. It was, I am convinced, the most significant turning point in my career,” said Dr. Niederhuber.
What attracted Dr. Niederhuber to oncology? “Working in cancer addressed my desire to perform surgery, which I dearly loved, but I also very much enjoyed being involved in internal medicine. And I always felt the best oncology surgeons were also talented internists as well. Oncology requires a team approach to clinical problem solving that is at once challenging and rewarding. I loved working side by side with my colleagues in medical oncology, radiation oncology, imaging and pathology to bring the very best care to complex cancer cases. I’ve always tried to instill that philosophy in the residents I’ve trained over the years,” said Dr. Niederhuber.
“I spent 19 very exciting years at the University of Michigan. Those years included serving as the Associate Dean for Research (1982-85), Senior Associate Dean and as interim dean along with Professor Peter Ward (1983-85). Dr. Ward, was also a tremendous mentor. For this service, University President Shapiro allowed me to take a sabbatical and I did so in Professor Tom Kelley’s department of Molecular Biology and Genetics at Johns Hopkins. The sabbatical got me back to the bench for a year and gave me a great chance to catch up on the rapid advances in molecular biology and genetics occurring at that time. At the end of the sabbatical year, I accepted an invitation to stay on the faculty at Hopkins. In 1991, I accepted an invitation by Dr. David Korn, Dean Stanford School of Medicine to head the Department of Surgery. This was followed by an opportunity to relocate to the University of Wisconsin to help them bring two separate NCI-designated cancer centers together under one NCI core grant and to direct that Center,” he recounted.
Road to the NCI
Throughout his career, Dr. Niederhuber has had many career-changing opportunities. In 2002, his friend and colleague, then–NCI Director Andrew von Eschenbach, MD, began recruiting Dr. Niederhuber to join him at the Institute, but Dr. Niederhuber needed to stay close to home to care for his young son and niece after his wife died from breast cancer in 2001.
“In 2005 I finally felt that things with the children had stabilized so I took a leave of absence from the University of Wisconsin and accepted a Deputy Director position at the NCI with Andy. I hadn’t been there more than a few weeks when President Bush appointed Andy as acting FDA commissioner and I became the acting Director of the NCI. I never expected that to happen and I must say it was a tremendous honor to have President Bush ask me in the summer of 2006 to become the Director. I remained in the position until the summer of 2010,” said Dr. Niederhuber.
During his tenure at the NCI, Dr. Niederhuber, working with Dr. Francis Collins, was instrumental in beginning The Cancer Genome Atlas (TCGA), an ambitious project that catalogs mutations responsible for cancer using genome sequencing and bioinformatics. TCGA has a number of different centers that are funded to generate and analyze data. “It remains a very successful project and during those early years we were able to learn a lot about infrastructure needs, bio-banking and bioinformatics. It certainly had a stimulatory effect on technology, advancing next-generation sequencing technologies which continue to give us a deeper knowledge of cancer genomics,” said Dr. Niederhuber.
Dr. Niederhuber is also recognized for his efforts to enhance the NCI’s intramural programs, the Cancer Center Program, and the SPORE program. He established the CTAC advisory committee to bring the leaders of clinical research together to address the many challenges of clinical research. When asked what accomplishments he was perhaps most excited about, he stated, “I believe there were two that would fall into the category. Certainly, I enjoyed very much starting the NCI’s Community Cancer Center’s Program (NCCCP) to bring the NCI into a closer relationship with smaller community hospital cancer programs in order to address issues such as disparities and to give greater access to clinical trials to patients that normally did not have such access. When I visited those NCCCP hospitals and saw how much of a difference we were making I was overwhelmed,” he said.
“The other program I am most proud of resulted from an opportunity to bring a group of physicists together and to get them excited about working in cancer research. They had never been involved with the NCI or with cancer as a research problem. We were able to fund some unbelievable science in this new program we called Physical Sciences in Oncology,” Dr. Niederhuber stated.
Pioneering Genomics Research
In 2010, Dr. Niederhuber left the NCI for yet another challenging opportunity. “I was introduced to Knox Singleton, the CEO of Inova Health System in northern Virginia. He was trying to figure out where genomics and personalized medicine fit with the future of Inova. In short, he wanted to distinguish Inova as a premier healthcare system, to compete with more established local academic institutions such as Johns Hopkins, for example. I recommended he expand a significant component of Inova’s activities around research, individualized medicine and education,” said Dr. Niederhuber.
After several discussions, Mr. Singleton approached Dr. Niederhuber with an offer. “He wanted me to build an institute within the Inova healthcare system centered on genomic medicine. It was a huge challenge, but since I could already see the impact of genomics on the future of cancer care, why wouldn’t I want to begin a large-scale predictive genomics project which started enrollment at birth and would follow patients over their lifetime to study a wide range of disorders? So I accepted,” said Dr. Niederhuber.
As Executive Vice President and CEO of the Inova Translational Medicine Institute, Dr. Niederhuber is leading a team of clinicians and researchers working on ground breaking genetic studies including the problem of preterm birth, a growing public health issue in the United States that costs our healthcare system more than $28 billion per year.
“We have more than 915 families enrolled in this study, where we’ve generated whole genome sequences looking for genetic markers that identify women at high risk of preterm births. We are seeing early results that indicate this information will help lead to better and faster diagnosis and care, as well as preventive therapies,” said Dr. Niederhuber. “We have also started a project which consents families during their early second trimester, follows them through delivery and then continues to follow the baby every six months. Again, this study involves family-trio whole genome sequencing and the integration of clinical information. We have over 1,250 families enrolled on our way to a longitudinal cohort of 5,000 families,” he said.
What Lies Ahead
During his illustrious career, Dr. Niederhuber has received numerous honors including election to the Institute of Medicine. He serves on several advisory boards, and continues to receive honorary professorships, and professional achievement awards. He has authored and coauthored more than 250 publications and edited 9 books, including serving as Editor-in-Chief of the highly regarded reference text Abeloff’s Clinical Oncology, currently in its fifth edition.
But Dr. Niederhuber’s career is measured more by what lies ahead than his past accomplishments. “We’re preparing to break ground on a large 350,000 sq. ambulatory cancer center here at the Inova Fairfax Medical Center and to launch new genomic studies of cancer. Our goal is to predict those with a higher risk for cancer and pinpoint the exact therapies that the individual patient needs to successfully treat the disease,” said Dr. Niederhuber, with the energy in his voice indicating his relish for the challenges that lie ahead. ■