$8.3 Million NIH Grant to Study Sarcoidosis, Alpha-1 Antitrypsin Deficiency Awarded
A multidisciplinary team at the University of Pittsburgh, which includes McGowan Institute for Regenerative Medicine affiliated faculty member Stephen R. Wisniewski, PhD, professor, Department of Epidemiology, and associate dean for research, Graduate School of Public Health, University of Pittsburgh, will be leading a national effort to explore the relationships between the bacteria that live in the lungs, gene activation patterns, and disease progression. The project aims to learn more about the causes and progression of two potentially deadly yet under-studied lung diseases, alpha-1 antitrypsin (A1AT) deficiency and sarcoidosis, as well as possibly to identify new treatments for them.
Funded by a 3-year, $8.3 million grant from the National Institutes of Health, 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, MD, PhD, 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.
“This study is an important step toward implementing personalized medicine approaches in chronic lung disease,” added co-principal investigator Dr. Wisniewski.
The GRADS program is sponsored by the NIH’s National Heart, Lung, and Blood Institute (NHLBI).
“This award highlights the commitment of the NHLBI to use cutting-edge molecular and genomics applications for the discovery of disease biomarkers to identify new diagnostic tools and targets for new therapies,” said James Kiley, PhD, director of the NHLBI Division of Lung Diseases. “It also underscores the NHLBI’s commitment to advance understanding of all lung diseases.”
In one of two projects, the researchers will use samples collected by GRADS centers to examine the hypothesis that changes in the microbial environment, or microbiome, 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.
Kevin Gibson, MD, professor, University of Pittsburgh Division of Pulmonary, Allergy and Critical Care Medicine, and clinical director of the Simmons Center, is the principal investigator of the local GRADS clinical center.
Other collaborating and clinical GRADS centers include Vanderbilt University; University of South Carolina; University of California, San Francisco; University of Illinois at Chicago; Yale University; the J. Craig Venter Institute; University of Pennsylvania; National Jewish Health; and Johns Hopkins University.
The GRADS genomics and informatics center is funded by NIH grant #1U01HL112707-01. Additional GRADS funding is provided by NIH grant # 1U01HL112711-01.
Illustration: University of Pittsburgh.