Alpha-1 antitrypsin deficiency (A1 AT), an autosomal recessive genetic disease that is associated with a variable risk of COPD, and Sarcoidosis, a systemic disease characterized by the formation of granulomatous lesions especially In the lungs, liver, skin, and lymph nodes that leads to a dramatically heterogeneous set of clinical manifestations, differ in etiology and clinicl presentation but share a variable and unpredictable course. To improve disease classification, facilitate biomarker discovery and accelerate advent of novel therapy an integrative approach that combines the results of clinical studies with molecular phenotyping results is required. The Sarcoidosis and A1 AT Genomics and Informatics Center (SAGIC) will facilitate this process by addressing the following objectives for the NHLBI Genomic Research In A1 AT and Sarcoidosis (GRADS) program: 1) Coordination of Clinical Centers activities that include patient recruitment and phenotyping and biospecimen collection. 2) Performance of transcriptome and microbiome analyses of the samples obtained by the Clinical Centers, 3) Data analysis and integration, 4) Dataset preparation for deposit in the NHLBI BloLINCC repository. The objectives will be addressed through two research projects. Project 1: A1 AT microbiome - will address the hypothesis that shifts in the lung microbiome determine the extent of lung involvement In A1 AT and that they are reflected in mRNA and microRNA changes in surrogate tissues, and Project 2: Novel molecular phenotypes in Sarcoidosis - will address the hypothesis that systemic Inflammation as reflected in gene expression changes in PBMC Is indicative of disease extent, microbiome shifts and granuloma molecular networks.

Public Health Relevance

Alpha 1 antitrypsin (A1AT) and sarcoidosis are lung diseases characterized by unpredictable course and potential significant morbidity. This research proposes transforming the understanding of these diseases by serving as a hub for NHLBI Genomic Research in A1 AT and Sarcoidosis (GRADS) program by performing two study wide research protocols: A1 AT Metagenome and New Sarcoidosis Molecular Phenotypes.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHL1-CSR-S (F5))
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Punturieri, Antonello
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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