After years of working with patients living with lung disease as a pulmonologist, Catherine Rufatto Sears, MD, of Indiana University understands the devastating impact of lung cancer and chronic obstructive pulmonary disease (COPD). As a physician scientist, she focuses her research on uncovering new clues about how these diseases interact, why they often occur together and how we may one day prevent them.
We currently know that COPD, and specifically emphysema, is not just a lung disease found alongside lung cancer; it increases a person’s risk of developing lung cancer. Additionally, when these two diseases overlap, treatment becomes more difficult. But despite this strong connection, scientists still don’t fully understand why they occur together. Dr. Sears’ research aims to change that.
The Role of DNA Repair in Lung Disease
Dr. Sears’ interest in lung cancer grew as a pulmonary and critical care fellow, where she first studied in understanding the role of DNA repair in lung cancer treatment response. However, driven by her practice as a pulmonologist in which she diagnosed patients with both COPD and lung cancer, she became intrigued by the number and complications of those with both lung cancer and COPD. These two major lung health problems are traditionally researched separately, but Dr. Sears wanted to explore how DNA repair deficiencies may contribute to the development of lung cancer, and how COPD/emphysema may be involved. “Many diseases that get a lot of attention, but lung cancer and COPD often aren’t included in that group. This is disappointing because they are both incredibly common but understudied,” she said. In fact, COPD is the fourth leading cause of death worldwide and lung cancer is the number one cancer killer, making these diseases truly devastating to much of the population.
DNA repair is our body’s natural way of fixing damage that happens inside our cells every day. When it isn’t working the way it should, mutations can build up increasing the risk of diseases like cancer. One particular repair protein, called XPC (xeroderma pigmentosum group C), is crucial in protecting our cells from damage. While true XPC deficiencies in humans are rare, even small weaknesses in the DNA repair system can raise someone’s risk for lung cancer.
During her early research, Dr. Sears made a key discovery. She found that when subjects with reduced DNA repair were exposed to cigarette smoke, they not only were more likely to develop lung cancer, but they were more likely to develop emphysema as well. This connection between DNA repair and both major lung diseases sparked the research she is leading today.
Smoke Exposure Patterns and Disease Development
Exposure to cigarette smoke is also a major factor in the development of both emphysema and lung cancer, so alongside DNA repair research, Dr. Sears and her team are studying the effect of cigarette smoke and other inhaled pollutants. “We wondered if the way and rate of exposure may change the likelihood of developing these diseases,” Dr. Sears explained. They were curious whether repeated continuous or intermittent exposure patterns may affect DNA repair differently. By using long-term exposure models, they hope to understand whether the timing and level of exposure changes the risk for lung cancer and COPD.
The data that Dr. Sears’ team has analyzed so far suggests that DNA repair is very important in this process. Though both exposure patterns can lead to cancer and emphysema based on the recorded changes in the lungs, the immune system seems to respond differently depending on the exposure pattern. “We are able to see that there are changes that happen in the short term that don’t go back to normal even when you take away the cigarette smoke,” she explained. They are currently digging deeper to discover what genes are being expressed in different cell types.
Previous research has strongly supported that changes in the epithelial cells, which are cells that line the airways and can become cancerous or damaged, are not the only important factor. Changes in immune cells, which control inflammation, are just as important for the development of these diseases. “We suspect, based on what we are seeing, that this interaction between the immune environment and the local epithelial cells in the lung are very linked,” she said.
Applying Findings to Help Patients
One of Dr. Sears’ biggest goals is to build better research models that more accurately mirror what happens in human lungs. Right now, most studies look at lung cancer or COPD alone. That approach leaves out the overlap that doctors see every day. If models don’t reflect real life, treatments that look promising in early research may fail once they translate to real patients. This kind of research could lead to major breakthroughs in how we diagnose, prevent and treat lung disease.
As science continues to move toward personalized medicine, this research may also help create new treatments tailored to the unique biology of each patient. “Exposures to pollution, radon, asbestos, radiation, other chemicals; all these things increase your risk of lung cancer,” Dr. Sears explained. “Though we are currently focusing on cigarette smoke, understanding why someone gets COPD or lung cancer or both, can later be applied to other areas of exposure that can be linked to these diseases.”
Learn more about Dr. Sears’ research and other research being done through the American Lung Association at Lung.org/research.
Blog last updated: January 7, 2026
