. Telomere diseases encompass a spectrum of rare and fatal syndromes caused by mutations in genes regulating telomere biology. These include the severe childhood blood disorder dyskeratosis congenita (DC) and later-onset lung diseases such as pulmonary fibrosis (PF). Despite progress in gene and pathway discovery in the past two decades, there has been no translation of this knowledge into therapies, and there are no curative treatments. Central to the pathogenesis of telomere diseases is disruption of telomerase, the ribonucleoprotein complex that replenishes telomeres in human cells. The long-term goal of this project is to therapeutically restore the long non-coding RNA component of telomerase, TERC, which is dysregulated in DC, PF and other telomere diseases. The
Telomerase is critical for human health and longevity, as revealed by genetic mutations that disrupt its function across a wide spectrum of degenerative disorders including aplastic anemia and pulmonary fibrosis. The overall objective of this proposal is to identify chemicals that restore levels of TERC, the essential non-coding RNA template of telomerase, to develop much-needed treatments for life-threatening lung and blood diseases.