David Schwartz, MD, distinguished professor of medicine and immunology in the University of Colorado Department of Medicine’s Division of Pulmonary Sciences and Critical Care Medicine, has spent his career advancing the cause of medical research on multiple fronts. When he isn’t helping to steer translational research, or boosting the careers of the next generation of physician scientists, or leading medical enterprises, he’s engaging in cutting-edge research of his own.
In the latter realm, Schwartz talks passionately of the prospect of “a disruptive therapeutic approach” to pulmonary fibrosis, an aggressive disease that attacks the lungs, mostly of people age 50 or older. There’s no cure short of a lung transplant.
It’s a disease that Schwartz has studied relentlessly for more than 30 years. And there’s ever-growing urgency in the work, he says, because “this disease is increasing in prevalence as our population ages.”
There still are many “unmet needs” surrounding pulmonary fibrosis, Schwartz says, including identifying biomarkers useful in early diagnosis and prognosis, as well as ways to predict “whose disease is going to progress more rapidly.”
Beyond that, he says, “We still don’t fully understand the underlying mechanisms that are relevant in the development and progression of the disease, and we need much more effective drugs that can treat the disease in its earliest phases and interrupt its progression.”
But Schwartz says he’s excited by what the next few years will bring.
“Within the next several years, we could have a drug that’s completely different from any other drug that’s now being used to treat pulmonary fibrosis,” Schwartz says. “Whether it will work or not is unclear, but I think it’s likely to work because it will get at the fundamental cause or initiating factors of the disease. And even if it doesn’t work, developing it will teach us an enormous amount.”
David Schwartz, MD (left), discusses pulmonary fibrosis for a 2019 CU podcast.
‘At the forefront of his field’
Schwartz’s career is marked by many achievements and milestones, including serving as chair of the CU Department of Medicine from 2011 to 2021. Formerly, he was director of the National Institute of Environmental Health Sciences at the National Institutes of Health and founding director of the Center for Genes, Environment and Health at National Jewish Health.
This year, Schwartz became associate dean for translational sciences in the CU School of Medicine, and he was named an inaugural recipient of the CU Anschutz Chancellor’s Distinguished Research Lectureship Award. Schwartz presented his award lecture, “From Discovery to Insight: Uncovering the Role of MUC5B in Lung Fibrosis,” on February 4.
“For decades, David has been at the forefront of his field,” Chancellor Don Elliman said in introducing Schwartz. “Over the course of an exceptional career, David has made countless contributions to our understanding of the development and progression of pulmonary fibrosis. His lab has numerous firsts in advancing knowledge of the disease’s origin and possible treatments, which he’s working on now. And among them is their discovery of key genetic variants that are critical to the development of the disease itself.”
VIDEO: David Schwartz, MD, presents the Chancellor’s Distinguished Research Lectureship on pulmonary fibrosis on February 24, 2025.
‘No one knows the cause’
Pulmonary fibrosis “comes on in a nonspecific way, meaning that it’s oftentimes misdiagnosed as something else, unfortunately,” Schwartz says. By the time it’s accurately diagnosed, patients often already have extensive lung fibrosis, or scarring, making it difficult to breathe and nearly impossible to treat.
The fibrosis “progresses rapidly, even on medication,” Schwartz says. “So while we have a couple of medications that slow down the rate of progression, these medications don’t affect overall mortality, and these drugs are not well tolerated. In fact, about 50% of people who develop the disease die within a five-year period even under the best of care.”
By the time most people get diagnosed, he says, “there’s already so much scar tissue that the patient is severely impaired and the fibrosis is progressive. That’s why we need a way to diagnose the disease at a much earlier stage and treat it before irreversible fibrosis is established.”
At his lecture, Schwartz talked of a 52-year-old patient he saw 30 years ago. “He was extremely short of breath. His chest X-ray was worsening despite multiple courses of antibiotics.”
The patient, a sister, and four of his brothers eventually died of pulmonary fibrosis. “What struck me was how a family could be wiped out by this disease, and the strength of the genetic signal,” Schwartz says.
At the time, he says, “no one thought that the sporadic disease was genetic. In fact, the disease was called idiopathic pulmonary fibrosis – idiopathic, meaning no one knows the cause.”
So Schwartz decided he needed to “wipe the slate clean and figure out a novel approach to this disease. Our focus was to figure out whether genetics play a role, and then to define the key gene or genes driving the development and progression of both the familial and sporadic presentation of lung fibrosis.”
→ A fatal lung disease has met its match at CU Anschutz
Left: David Schwartz, MD, discusses pulmonary fibrosis in a 2019 photo. Center: Schwartz receives the Chancellor’s Distinguished Research Lectureship Award from Lori Sussel, PhD, associate vice chancellor for basic science research, on February 27, 2025. Right: Schwartz gives his lungs a workout on a ride over Vail Pass.
‘A shocking finding’
Schwartz and collaborators launched their hunt for a fibrosis gene in the late 1990s. They started by identifying families with two or more cases of the disease, and focused on identifying the gene or genes associated with the familial disease and then planned to study the genetics of the more common sporadic presentation of idiopathic pulmonary fibrosis.
About 15 years of work led to the discovery that a variation in the MUC5B gene, which helps to produce and secrete mucus in the lungs, “is the dominant risk factor for the development of pulmonary fibrosis,” he says. The variation – labeled rs35705950 – “is associated with about 50% of the people who go in to develop pulmonary fibrosis. That was a shocking finding.”
Schwartz’s team also found that the rs35705950 variation was associated with a 20- to 30-fold increase in production of MUC5B in the lungs, killing cells and stimulating scarring.
In a breakthrough 2011 paper, Schwartz and his colleagues – including several from CU Anschutz and National Jewish Health – declared idiopathic pulmonary fibrosis as largely a genetic disease, “with one gene variant that causes the lion’s share of the problem.” Hundreds of investigators around the world soon replicated the results. “It was very gratifying to see this,” he says.
Schwartz went on to investigate how MUC5B with the rs35705950 variation could be used as a biomarker for early diagnosis and predicting risk for various types of pulmonary fibrosis. They also pinpointed the location in the lung most impacted by the gene.
“Now we had a molecular target and a specific location in the lung expressing that target,” he says. “And that’s when we decided to spin off a company in 2017.”
The company is Eleven P15 – named for the chromosomal location of MUC5B. It’s devoted to discovering novel genetically-targeted therapies to prevent and treat pulmonary fibrosis. Its scientific team includes several of Schwartz’s CU Anschutz and National Jewish Health colleagues.
“It’s based in my garage,” Schwartz says with a smile. “I figured Steve Jobs did pretty well in his garage, so I decided to do the same.”
A PowerPoint slide from an Eleven P15 presentation features David Schwartz, MD's garage, where the company is based.
Environmental exposures
Schwartz’s current work has three main goals, he says: “One, and most importantly, we are developing genetically based treatments for pulmonary fibrosis that stops the disease from progressing. Two, we are developing biomarkers to identify people before they develop extensive scarring in their lungs so we can treat them at a much earlier stage of their disease. And three, we need to understand the pathogenesis of the disease in a much more sophisticated way so treatments can be targeted in a way that produces more benefits and fewer side effects.”
The National Institutes of Health has backed Schwartz’s work on pulmonary fibrosis with a series of major grants.
While hunting for treatments, Schwartz is studying pulmonary fibrosis on other fronts.
“Fibrosis in the lung follows the airway, which means that something that you’re breathing in causes people to develop a response dictated by whether you’re genetically susceptible or not,” he says. “So we have a variety of studies where we’re looking carefully at environmental exposures to try to figure out whether it’s cigarette smoke, air pollution, heavy metals or other particulate matter, microplastics, or other inhalants that could help stimulate a fibrotic reaction.”
Schwartz speaks of many “incredible people” who have been his research partners for decades, many of whom are CU faculty members or at National Jewish Health, including his lab partner, Ivana Yang, PhD.
‘It was so emotional for me’
Since stepping down as CU Department of Medicine chair four years ago, Schwartz has been able to devote more time to research, but he works about 50% of his time in his role as director of the CU School of Medicine’s Program to Advance Physician Scientists and Translational Research.
“It’s a unique program,” he says. “Physician scientists are important in the research enterprise because they bridge the translational gap between basic science and medicine. We have about 100 people who we’re working with in that program, from post-baccalaureate students to senior professors, all interested in developing different types of translational research programs, attacking unmet needs in basic science and clinical medicine.”
Schwartz talks of a time when he and his CU Department of Medicine colleague Mark Steele, MD, were on the faculty at Duke University together in the early 2000s.
“We were talking to a group of maybe 100 patients and their families about pulmonary fibrosis. Most of the patients were on oxygen, and all you could hear through the entire discussion was their oxygen activating and deactivating. It was so emotional for me to hear those sounds and to know that these people were likely going to die from their disease in the next several years. I sat down and told them how helpless I felt, and how all of us needed to do more. All of us shed a tear.”
He adds: “That stimulated me to accelerate my research in lung fibrosis, because of all the people who were dying from the disease, all of the people at risk of this devastating disease, and the families that were affected by their relatives who are so impaired.”
Photo at top: David Schwartz, MD, presents the Chancellor’s Distinguished Research Lectureship on pulmonary fibrosis on February 24, 2025.
