Asked if there’s a lesson for other medical researchers in his decades-long career, York Miller, MD, says it’s this: “If you see something promising, don’t be reluctant to change direction.”
That philosophy has led to decades of important work on lung cancer by the University of Colorado Cancer Center member and CU Department of Medicine professor of pulmonary sciences. And now, that work has resulted in national recognition of Miller’s career.
Miller has been presented with the annual Lifetime Achievement Award by the Thoracic Oncology Assembly of the American Thoracic Society (ATS), honoring “an established, internationally recognized individual with a record of sustained exemplary achievement.” He received the award in May at the ATS’ annual meeting in San Diego.
“Obviously, I love it,” Miller, a staff physician at the Rocky Mountain Regional Veterans Affairs Medical Center, says of the award. “It’s been presented to quite a distinguished group of people who’ve made big contributions over the years, so I’m happy to be a member of that group.”
Miller’s list of achievements is long. He holds the Thomas L. Petty Endowed Chair in Pulmonary and Critical Care in the CU Division of Pulmonary Sciences and Critical Care Medicine. He has served as a leader of the CU Cancer Center’s Lung, Head, and Neck Cancer Program, and he is a member of the cancer center’s Thoracic Oncology Research Initiative (TORI).
Miller was elected to the American Society for Clinical Investigation in 1990, and he has served as deputy editor of ATS’ American Journal of Respiratory and Critical Care Medicine.
Focus on patients at risk
Miller, who earned his MD at Duke University in 1976, says he has been interested in probing the secrets of lung cancer since he began seeing patients with the disease during his pulmonary fellowship training at CU in the early 1980s. And many of his VA patients have lung cancer.
“As pulmonary doctors, we’re often the first people to see patients with lung cancer, and we guide them through the appropriate pathways either to oncology, radiation therapy or surgery,” he says. “Pulmonary physicians also are focused on patients who are at risk of getting cancer.”
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Miller’s early research focus was on cancer cell genetics, including a 1989 investigation of the role of chromosomal deletion – the absence of a small piece of DNA in cells – and the enzyme aminoacylase-1 in small cell lung cancer. “I started out being interested in assigning genes to chromosomes, which is something no one does anymore, but at the time it was cutting edge,” he says.
Eventually, Miller’s research shifted to exploring patients’ susceptibility to the development of lung cancer and ways to reduce that susceptibility. Miller and his colleagues analyzed cohorts of high-risk patients to assess biomarkers of risk for lung cancer, as well as investigate the biology of premalignant lesions accessed during bronchoscopy.
Repairing damage
More recently, Miller – working as a leader of the CU Colorado Pulmonary Premalignancy Program – has focused on understanding natural reparative processes in the lungs, developing ways to bolster those processes and prevent the evolution of premalignancy to cancer.
Collaborating with Robert Keith, MD, also a CU Cancer Center member and a pulmonary sciences professor, and Mark Geraci, MD, now at the University of Pittsburgh, Miller’s group launched a clinical trial of the drug iloprost, used to improve blood flow, as a way to help prevent lung cancer. The iloprost trial is the only one to date to have met the endpoint of improving endobronchial premalignancy, Miller says.
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Years later – working with Moumita Ghosh, PhD, a CU Cancer Center member who’s a developmental biologist and associate professor in pulmonary sciences – “we discovered that iloprost stimulates progenitor cell function to repair damaged epithelium,” he says. “We think that’s perhaps an important way to prevent cancer. The risk of cancer goes up as you age and your ability to repair damage goes down. This drug, we think, has the potential to improve repair of the epithelium in the airways and, in that way, prevent cancer.”
Attacking lesions
Miller and Keith have followed up on research by two other CU Cancer Center members – CU pathologist Daniel Merrick, MD and Raphael Nemenoff, PhD, of the CU Division of Renal Diseases and Hypertension – focused on premalignant lesions in the central airways of former smokers and what makes those lesions either regress or progress. In the lesions that spontaneously regress, there is a strong gene-expression signature of antigen presentation and immune activation, Miller says.
“We’ve done an early trial in humans where we’ve given a checkpoint inhibitor that stimulates the immune system, and it seems to be having a strong effect to make these premalignant lesions go away,” Miller says. Results of a phase 1 clinical trial without a placebo have been encouraging enough that Miller and Keith hope to get NCI backing for a phase 2 trial.
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Miller says he is grateful for the resources and support he has received on the CU Anschutz Medical Campus and at the VA Medical Center, and he is quick to credit “all the talented people” he has worked with over the years, as well as the patients who have volunteered to have their tissue studied.
Of the various twists and turns in his research pursuits, Miller says: “There’s always a strain between becoming diffuse and unfocused, or being so focused that, when an amazing opportunity crosses your path, you don’t follow up on it. If life gives you an opportunity, you should follow up on it, even if it’s not in your plan.”
Photo at top: York Miller, MD (left) is presented with the Lifetime Achievement Award by the Thoracic Oncology Assembly of the American Thoracic Society by Christopher Slatore, MD, of the Oregon Health Sciences University, at the ATS’ annual meeting in San Diego in May 2024. Photo courtesy of York Miller.
