Weill Cornell Medicine in New York City has received a $2.1 million government grant to study a mechanism underlying lung and kidney scarring.
The National Heart, Lung and Blood Institute grant will allow Drs. Mary E. Choi, her husband, Augustine M.K. Choi, and other researchers at the medical school to investigate the RIPK3 gene’s role in fibrosis. The heart, lung and blood institute is part of the National Institutes of Health.
Weill Cornell is one of three institutions to win a grant in response to the institutes of health’s call for “Collaborative Projects to Accelerate Research in Organ Fibrosis.”
“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,” Mary Choi, a Weill Cornell kidney expert, said in a Cornell news release.
“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,” added Choi, whose husband, a lung expert, is dean of Weill Cornell Medicine.
The researchers will build on studies in mice showing that the gene is involved in fibrosis formation and progression, and in regulating a form of programmed cell death called necroptosis.
Scientists who conducted those studies engineered mice to have no RIPK3 gene. Lack of the gene protected the animals against kidney fibrosis, but not against lung fibrosis. This suggested organ-specific differences in RIPK3’s mechanism of action.
Weill Cornell researchers will use RIPK3 inhibitors to regulate the gene’s kidney and lung pathways in mice and in human tissue grown in a lab. They will also use a low dose of carbon monoxide to try to inhibit fibrosis. Previous research that they conducted showed that the gas can help regulate cell death and may slow the progression of fibrosis.
“There are two avenues for potential human therapy [from the research] — the specific inhibitor for this protein or the use of carbon monoxide gas to target this pathway,” Augustine Choi said. “Ultimately we want to make a difference in patients by discovering innovative treatments.”
The kidneys and lungs, although separate organs, may actually share a communication platform, the team said.
“Although they are physically distant in the body, there is evidence of communication between the kidney and the lungs, with the two organs displaying a connection in various diseases,” Mary Choi said.