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NIH Awards Yale Researcher $3M to Study Genomics of Idiopathic Pulmonary Fibrosis

NEW YORK (GenomeWeb) – The National Institutes of Health has awarded a Yale University researcher a four-year, $3 million grant to investigate the molecular networks that underlie the histological features of idiopathic pulmonary fibrosis (IPF), with the goal of better understanding the disease and eventually developing therapeutic interventions.

IPF is a progressive disease characterized by scarring of lung tissue, which hinders the lung's ability to transport oxygen. It has no known cause and the only available treatment is lung transplantation.

According to Yale's Naftali Kaminski, the disease has a number of well-established histopathological features including alveolar cell hyperplasia, an abundance of myofibroblast foci, and aberrant remodeling.

Additionally, he and other investigators have identified distinct patterns of mRNA and microRNA expression, as well as global changes in DNA methylation, in IPF lungs. Such efforts, however, have not specifically compared the characteristics of lung tissue at different stages of the disease.

"Until we start getting into the lung microenvironments and see … whether we can distinguish changes within the IPF lung … we won't be able to understand it's pathogenesis and what we actually need to block to reverse the disease," he told GenomeWeb.

With the support of the NIH grant, he and collaborators now aim to investigate the genomic and transcriptomic profiles of various histologically defined regions of IPF lungs obtained from patients who have undergone lung transplants.

This will include the generation of mRNA, miRNA, and epigenomic profiles of differentially affected regions of diseased lungs using microCT-guided microdissection, next-generation sequencing, and laser capture microdissection-reduced representation bisulfite sequencing, according to the grant's abstract.

The research team also aims to determine how specific cells influence genomic and epigenomic changes in IPF by examining distinct cell populations obtained from individuals with and without IPF at baseline and in response to fibrosis-like perturbations.

Kaminski noted that data generated through this project will be incorporated into a searchable, web-based resource called IPFmap, which he previously established with University of Pittsburgh scientist Panagiotis Benos.

Kaminski's grant began on August 14 and runs until the end of May 2019.

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