Please describe the research questions of your lab.
My laboratory studies why some individuals exposed to cigarette smoke, e-cigarette/vaping aerosols, cannabis smoke, and other inhaled exposures develop COPD, emphysema, and related respiratory diseases, while others do not. We are particularly interested in identifying the molecular pathways that drive COPD susceptibility, disease progression, exacerbation risk, and heterogeneity across patients. Much of our work integrates large clinical cohorts, including COPDGene and SPIROMICS, with genomics, transcriptomics, proteomics, metabolomics, imaging, and clinical phenotyping. A major focus is the discovery and validation of biomarkers that can help define COPD endotypes, predict progression, and identify therapeutic targets. We are especially interested in pathways involving RAGE and RAGE ligands, epithelial injury and repair, innate immune activation, metabolic dysfunction, iron biology, and mechanisms linking systemic inflammation to lung disease. The long-term goal is to move beyond broad clinical labels such as “COPD” toward a more mechanistic understanding of disease (endotyping) that can guide prevention, diagnosis, and treatment.
What genetics/genomics techniques do you utilize in your lab?
Our lab uses a broad range of multi-omic approaches, including genome-wide association studies, whole-genome sequencing, expression quantitative trait locus and protein quantitative trait locus analyses, transcriptomics from blood and airway epithelial samples, integrative multi-omics, pathway analysis, and network-based methods. We frequently combine genetic data with proteomic, metabolomic, imaging, and clinical data to identify biologically meaningful pathways in COPD. We also use genomic data to help interpret biomarkers, distinguish causal biology from correlation, and identify patient subgroups that may respond differently to specific interventions.
Describe a key technique/assay/instrument utilized in your lab, and what questions can it answer.
A key approach in our lab is high-throughput plasma proteomic profiling, including SomaScan-based aptamer proteomics and complementary immunoassay platforms. These technologies allow us to measure thousands of circulating proteins in large numbers of deeply phenotyped participants. This helps us ask which biological pathways are associated with emphysema, airflow obstruction, exacerbations, imaging progression, and clinical outcomes. Proteomics is especially useful because proteins are closer to disease mechanisms and therapeutic targets than many upstream molecular measurements. We combine proteomic data with genetics, transcriptomics, metabolomics, and CT imaging to identify COPD endotypes, nominate biomarkers, and prioritize pathways for mechanistic follow-up.
At what point in your life did you decide you wanted to be a scientist/physician?
I have always wanted to be a scientist. I cannot remember a time when it wasn’t top of the list, but it did compete with wanting to be a pilot and astronaut in my pre-teen years. My first peer-reviewed publication was accepted when I was 19.
In your opinion, what is one of the most important discoveries in the field of respiratory illness/disease/function?
One of the most important discoveries in respiratory disease is that COPD is not a single uniform disease, but a heterogeneous syndrome with multiple biological pathways, clinical trajectories, and imaging phenotypes. This recognition has changed how we think about COPD research. It has moved the field from simply measuring airflow obstruction toward understanding emphysema, airway disease, exacerbation risk, systemic inflammation, genetic susceptibility, and molecular endotypes. This shift is essential for developing precision-medicine approaches to prevention and treatment.
Briefly describe your favorite publication that you were involved with, in general-audience terms.
One of my favorite publications is Sun W. et al., “Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD,” PLOS Genetics, 2016; PMID: 27532455. This paper was important because it showed that blood biomarker levels are not determined only by disease activity, but also by common inherited genetic variants. In two large NIH-supported cohorts of smokers, COPDGene and SPIROMICS, we measured blood biomarkers and paired these data with genome-wide genetic information. We found many genetic variants that strongly influenced protein biomarker levels, known as protein quantitative trait loci, or pQTLs.
I like this paper because it addressed a fundamental translational problem: when we measure a biomarker in blood, are we seeing lung disease biology, inherited baseline differences, assay biology, or some combination of all three? The study helped establish that genetic context can substantially improve biomarker interpretation in COPD. This was personally satisfying because it connected genetics, blood biomarkers, and clinically meaningful COPD phenotypes such as emphysema in a way that helped move the field toward more rigorous precision-medicine approaches. More broadly, the paper helped frame pQTL analysis as an essential tool for understanding which biomarkers may reflect causal disease pathways and which may primarily reflect inherited variation in protein levels.
What is your favorite aspect of ATS?
My favorite aspect of ATS is the way it brings together clinicians, basic scientists, geneticists, computational biologists, epidemiologists, and translational researchers around shared problems in lung disease. I have particularly valued the Section on Genetics and Genomics because it provides a home for investigators who want to connect molecular discovery with clinical respiratory medicine. ATS has also been an important venue for collaborations, mentorship, leadership, and building multidisciplinary communities around COPD, omics, biomarkers, and precision medicine.
How could your research assist scientists and clinicians in other assemblies at ATS?
Our research can help other ATS assemblies by providing molecular tools and frameworks to better classify patients, interpret clinical heterogeneity, and identify pathways that may be relevant across lung diseases. Biomarkers, genetics, proteomics, transcriptomics, metabolomics, and imaging-based endotypes are not limited to COPD. Similar approaches can be applied to asthma, interstitial lung disease, pulmonary vascular disease, critical illness, environmental and occupational lung disease, and sleep-related disorders. By integrating molecular data with clinical outcomes, our lab can help clinicians and scientists identify patient subgroups, prioritize therapeutic targets, and design more mechanistically informed clinical studies.
Would you be open to collaborations with SGG and/or non-SGG scientists and clinicians? Do you have any potential lab openings currently or in the near future?
Yes. I am very interested in collaborations with SGG and non-SGG scientists and clinicians, particularly projects involving COPD, smoking and vaping-related lung disease, biomarkers, multi-omics, genetics, imaging, and translational cohort studies. I welcome collaborations that connect molecular mechanisms with clinically meaningful outcomes. I am also interested in mentoring trainees and junior investigators who want to work at the interface of respiratory medicine, genomics, computational biology, and translational science. Potential openings vary over time, but I am always happy to hear from motivated students, fellows, postdoctoral researchers, and collaborators with aligned interests. We currently have multiple trainee and faculty positions open in my department for trainees and faculty: https://www.lerner.ccf.org/genomic-medicine/careers/
Please include your email address or lab website to share with potential collaborators.
Potential collaborators can learn more through the Bowler Lab page at Cleveland Clinic Research.
Email: BowlerR@ccf.org