Project Overview
There is growing interest in understanding the shared mechanisms of differing ILD subtypes and whether this may provide insights into prognosis and effective treatment. Dr. Wolters’ lab has demonstrated many similarities between idiopathic pulmonary fibrosis (IPF) and a subset of non-IPF ILD that has a disease pattern called usual interstitial pneumonia (UIP), which includes 25-30% of scleroderma ILD patients (SSc-UIP).
The Wolters group showed that non-IPF UIP patients are characterized by telomere dysfunction and increased cellular senescence, two processes that may contribute to lung disease. Telomeres are the “caps” on the ends of chromosomes that protect the stability of chromosomes and telomere dysfunction has been associated with aging and disease. Cellular senescence is a process by which cells age and stop dividing, but don’t die; instead, senescent cells release molecules that trigger inflammation and tissue remodeling.
The Wolters group specifically showed that in non-IPF UIP pattern disease, including SSc-UIP, telomere shortening was happening in type II alveolar cells, surfactant-secreting lung cells, which are also thought to malfunction in IPF. They also showed that cellular senescence was increased in non-IPF UIP, including SSc-UIP. Dr. Wolters’ group is currently using single-nuclei-RNA-seq to identify additional shared pathways and cell types between SSc-ILD and IPF.
