A multidisciplinary team at the University of Pittsburgh will be leading a national effort to explore the relationship between the bacteria that live in the lungs, gene activation patterns, and disease progression. The project, funded by a three-year, $8.3 million grant from the National Institutes of Health, intends to learn more about the causes and progression of two potentially deadly yet under-studied lung diseases, alpha-1 antitrypsin (A1AT) deficiency and sarcoidosis. Researchers hope that such study will help to identify new treatments for them.
“This study is an important step toward implementing personalized medicine approaches in chronic lung disease,” said co-principal investigator Stephen R. Wisniewski, Ph.D.
, professor, Department of Epidemiology, and associate dean for research, Graduate School of Public Health, University of Pittsburgh.
The Genomic Research in A1AT and Sarcoidosis study (GRADS) Genomics and Informatics Center will obtain patient samples from seven clinical centers across the nation and use a combination of sophisticated genome and microbiome profiling techniques with advanced computational methods to identify biomarkers that indicate the current status of the lung diseases and predict their progression and response to the therapy, explained lead-principal investigator Naftali Kaminski, M.D., professor, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine, and director, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease.
“Integrating genome, microbiome and clinical information has never been done in sarcoidosis or A1AT,” he said. “The insights from this study may dramatically change the understanding and management of both diseases.”
Co-principal investigator Michael Becich, M.D., Ph.D., professor and chair, Department of Biomedical Informatics, Pitt School of Medicine, noted that the study team included experts in genomics, pulmonary medicine, epidemiology, medical bioinformatics, computer science, quantitative imaging, computational biology, sequencing, and microbiome and virome research.
“This coordinated, multidisciplinary effort will ensure that data are not only obtained, but also analyzed and shared with the scientific community,” he said.
In one of two projects, the researchers will use samples collected by GRADS centers to examine the hypothesis that changes in the microbial environment of the lung influence the severity of A1AT deficiency, an inherited disorder in which the body does not make sufficient amounts of the A1AT protein leading to early lung and liver disease. The researchers also hope to find biomarkers of disease status in the sputum.
The second project will explore whether shifts in immune regulation and in the microbiome population can indicate and predict the severity of sarcoidosis, a disorder of uncontrolled inflammation that can affect any organ, but typically starts in the lungs, skin and lymph nodes and is characterized by a highly variable and unpredictable course.