Weill Cornell Medicine researchers have received a grant from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health to conduct an in-depth study of the mechanisms that cause fibrosis to form in the lung and kidney.
The competitive grant was one of only three awarded nationally this year by the NIH and will provide more than $2.1 million in funding over four years.
Researchers will study the pathogenic process that causes fibrosis,. The investigators will focus on a gene called RIPK3 and the role it plays in the development of lung and kidney fibrosis. They will also seek to uncover new biomarkers for disease severity and new molecular targets for diagnosing and treating patients whose lungs or kidneys are affected by the condition.
“Almost any chronic disease that progresses to an end stage, such as lung or kidney disease, leads to fibrosis that is ultimately responsible for organ failure,” said Dr. Mary Choi, a professor of medicine and nephrologist at Weill Cornell Medicine. “Still, there are very limited treatment options specifically targeting this. So we want to address that by investigating what leads to progressive fibrosis in chronic disease.”
In previous preliminary studies, the investigators discovered that the RIPK3 gene, which plays a key role in regulating a programmed cell death pathway called necroptosis, is significant in fibrosis formation and progression. The gene codes for a common type of signaling molecule in cells called protein kinase. Using genetically engineered mice, the team has demonstrated that rodents lacking RIPK3 were protected against kidney fibrosis, yet susceptible to pulmonary fibrosis. The organ and tissue-specific differences may therefore be due to the different signaling pathways through which RIPK3 acts.
Armed with the NIH grant, the investigators now seek to characterize the function of RIPK3 and the molecules that it targets to exert its varied effects on kidney and lung fibrosis.