Nancy Hadley-Miller, MD, MS, is a Professor of Orthopaedic Surgery, faculty of Human Medical Genetics and Genomics Program at the University of Colorado and the Medical Director of Research in the Musculoskeletal Research Center in the Pediatric Orthopedics section at Children’s Hospital Colorado where she is an active clinician scientist within the Pediatric Orthopaedic section. Dr. Miller’s research as primary and collaborating investigator have received over $9.5 million in support. From 2018 to 2022 she was a permanent member in the Genetics of Health and Disease (GHD) Study Section of the National Institutes of Health (NIH) and served as Chair of the GHD Study Section from 2020 to 2022. She is on the editorial boards of Journal of Pediatric Orthopaedics and Spine Deformity. Her research has been acknowledged and awarded within prominent venues including the Scoliosis Research Society (Hibbs award), Orthopaedic Research Society (Young Investigator award, New Investigator Recognition award), Cotrel Fondation, and POSNA, and she is active within the ORS, Human Society of Human Genetics, and ASBMR.
Dr. Miller’s major research focus has been the etiology of idiopathic scoliosis (IS) through an active basic science laboratory. Over the past 30 years, she has developed a large, well-defined biobank of both individuals and families with IS (including 3000 individuals from 700+ families) enabling examination of the genes, molecular pathways, and functional mechanisms, which relate phenotype and spinal axial development.
She attributes her comfort in entering a male dominated field simply from coming from a family of all men: all brothers! “And so being in a company of men was very normal to me.” She describes her father as a huge sports fanatic. He was an educator, a teacher, and then went into the military. He joined the Air Force around the time of the Korean draft where he met her mother teaching in Iowa. Dr. Miller was born in England and spent many formative years there. “England was really kind of my home place, … it's kind of one of those things where you look back and I'm probably most comfortable there than anywhere.”
Her parents, as educators, inspired awareness of local communities and they travelled extensively with their family in Europe before settling back in the DC area. She went on to be very successful at a small all girls high school, becoming class and school president. She ultimately attended Harvard for her undergraduate studies. It was there, by coincidence, that she encountered students rowing, and it fondly reminded her of England. She signed up for women’s crew, was flyweight, and then coxed and was captain. In her freshman year, they won the US championships in Philadelphia. They went to Moscow, Canada, the Netherlands, Holland, England, all rowing. Her crew experience defined her college life and was “just a hell of a lot of fun and discipline.”
Dr. Miller double majored in biology and art and initially was accepted to art school but elected to pursue a PhD program at Georgetown University in immunology that eventually evolved into a master’s degree. This ended up overlapping with medical school at the University of Maryland: a full-time student at two places for one year. In the meantime, she worked at the NIH in the Cancer Center and published on pancreatic cancer. Her mentor at the NIH introduced her to the operating room and at that time realized she was a surgical personality.
As an athlete, she was drawn to sports surgery and orthopaedics. James Gamble helped to inspire her interest in pediatric orthopaedics as a mentor who allowed her a first surgical experience. “That kind of thing, as we all know, just sets you up for… enthusiasm.”
Dr. Miller went on to Boston University for residency in orthopaedic surgery in 1987. “I was the first and only woman at BU at that time, which was a unique challenge particularly given my size.”
She then moved to Iowa, primarily for the mentorship of Dr. Stu Weinstein. “He was the reason I chose that fellowship for training… I wanted a fellowship to 'get into someone's head' - and it was him. Just to see how he handled things, how he thought.” She worked on long-term follow up with hip dysplasia and cartilage damage.
She refers to Dr. Ignacio Ponseti as “Papa.” “Papa’s work with clubfeet was not really known then, but he came with the fellowship as emeritus professor. So, Stu was the icing on the cake, and Papa was the cherry on top!”
She ended up staying a second year at Iowa further pursuing bench research finding inspiration to investigate scoliosis inspired by Ignacio Ponseti: “…not a lot of people know, but Ponseti's true love of life at that time was to discover the reason for scoliosis. He had two biochemists at Iowa that he had done quite a bit of work with to discover scoliosis etiology. As my second year started, he stuck a couple of papers in my mailbox on the new discovery of FBN1 as the gene responsible for Marfan’s disease. Dr. Ponseti thought that something in the connective tissues might be related to idiopathic scoliosis. And so that's really where this experimental quest started.”
“I found a lab at Iowa to work in under Dr. Michael Solursh, a developmental embryologist, and started harvesting different tissues from surgeries from 23 scoliosis individuals at various points along the curvature. I was running more than 120 different cell line cultures in the lab.” With these cultures, Dr. Miller was doing some relatively sophisticated experiments looking at FBN1 through immunoprecipitation intracellularly and with expulsion from the cell into the extracellular matrix. She received a lot of enthusiasm for her line of inquiry. During her first job at Baylor in the Shrine unit in Houston, “Dr. Cowell, editor of JBJS, called me, and said that my manuscript submission is exactly what we need. We need to be aware of more basic science in orthopedics.”
In Houston, William Horton was a pediatric geneticist interested in skeletal dysplasia who was based at the Houston Shrine. Bill Horton had the second floor of this two-story building as his lab, mostly related to skeletal dysplasia. Dr. Miller befriended him and forged a connection with his research and orthopaedic surgery. “When I wrote my first OREF grant, he said: ‘If you get this grant, you can have a bench.” Fortunately, I did get the grant, and so I got a lab bench!
“There was no sequencing back then. You had to look at what was known as tandem repeat polymorphisms or STRPs. You had to pour gels that were two feet by three feet to determine molecular density. All of this has changed. My career really has truly followed the advances of molecular sequencing and genetics.”
Within the clinic environment, it was apparent that there were many families with scoliosis. The thought was if there was something in the genome related to all the people in the family that have scoliosis versus not, maybe that would be a clue to where the ‘gene’ might be. That is how Dr. Miller’s family linkage studies began. A lot of her academic focus over time has been in familial idiopathic scoliosis disease.
She was recruited to Johns Hopkins by Dr. Paul Sponseller, who was extremely interested in basic science. “My family was there: My mother and dad, three brothers, and multiple nieces and nephews. It was nice to go back to Maryland. I love the East Coast… and life was good at Hopkins. I was the first operative woman surgeon there within orthopaedics. I had a lab and was very fortunate to be able to collaborate with the Genome Branch of NIH for statistical analyses, which was a key factor in moving the research forward.” Simultaneously, Dr. Miller was nurturing her growing family—two daughters and one son. She now has three grandchildren.
Dr. Mark Erickson then recruited her to Colorado to aid in the neuromuscular area and to enhance research efforts, as there was not much research being done in orthopaedics at the time in Colorado. However, the Department of Pediatrics was one of the top five in the country with significant NIH funding giving great credibility to the institution. Dr. Miller helped to build what's known as the MRC, or the Musculoskeletal Research Center. With a catchment area of about seven states, the clinical volume that passed through their practice is staggering—it just needed to be captured for clinically based research. Over time the MRC has become extremely productive, putting pediatric orthopaedics from Colorado on the academic map.
Over time, Dr. Miller was able to recruit Dr. Karen Payne from Pittsburgh to join the department to enhance stem cell research. A clinical case related to a physeal bar resection and a small grant from the hospital and the School of Mines in Boulder enabled them to propose a stem cell project related to the growth plate. This collaboration has blossomed into three NIH grants, multiple podium presentations at ORS and other international meetings. This work continues, and Dr. Miller says, “is a true example of how the intersection of clinical work and science can forge scientific avenues for translational work that can impact patient care.”
University of Colorado’s relatively new chair, Dr. Evalina Burger made a huge commitment to research approximately 5 years ago. They attracted a group of researchers from Rochester to run the research section. Dr. Miller felt like “we needed something like this to push us forward. And they have brought in significant federal funding, including a recent ARPA grant looking at developing a treatment for osteoarthritis.”
Dr. Miller believes her biggest accomplishment is to be a clinician scientist, for most of her years as a full-time clinician. She particularly loves limb deformity, clubfoot, and hip dysplasia. Within her clinical work she thinks:
“The biggest thing is to be able to connect the clinical world with the research questions that we should be asking. And if you don't marry the two? We lose sight of what we're doing or can do to benefit our patients. There's always going to be something to operate on. Why are we actually doing what we're doing? I think that what I'm most proud of is the aspect of keeping that scientific question behind what you are doing as physicians.”
She notes that the integration of science and clinical practice do not come to fruition without engaging the scientists. “Karen Payne didn't really know what a physis was, and now she has NIH grants. We have a lot of unsolved questions, and we need to keep engaging and talking to the scientists, to enable us to move forward in meaningful ways for patient care.
It's not that we're going to eliminate surgery. There's always going to be an element of the humanness of the patients that we see. There's always going to be an element of decision-making. That is the art of medicine that's always going to be there. But if we come at that with an understanding of the science behind what we're seeing, then we are doing the best for our patients.”
Dr. Miller’s advice is to find your passion, find your niche: “what gets you up in the morning. In this country, peds ortho is evolving into a very sub specialized group. In academics, again, find your niche. If not in academics, you still need to find a way to sustain your education to stay up with what is best for your patients in your clinical practice.”
Since her family has grown older, she has found more time to explore her love for mission work that began when she first started at the Shrine in Texas and perhaps was inspired by her worldly upbringing. She dedicates volunteer time now to provide care for children in South America through Advance.
Biography written by Dr. Sarah Nossov on behalf of the History & Hall of Fame Committee
