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Cedars-Sinai receives $12 million from NIH to investigate deadly lung conditions

Cedars-Sinai receives $12 million from NIH to investigate deadly lung conditions

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A scientific team led by Cedars-Sinai has been awarded $12 million from the National Institutes of Health (NIH) to investigate two deadly lung conditions: idiopathic pulmonary fibrosis and chronic lung allograft dysfunction.

Idiopathic pulmonary fibrosis, which scars lung tissue and obstructs breathing, affects more than 100,000 people in the U.S. While the course of the disease often is unpredictable, patients typically die within five years of diagnosis, according to the U.S. National Library of Medicine. “Chronic lung allograft dysfunction” refers to various complications that cause lung transplants to fail, resulting in fatalities.

Both conditions are poorly understood, said Paul Noble, MD, director of the Women’s Guild Lung Institute and professor and chair of the Department of Medicine at Cedars-Sinai. “Doctors can treat some symptoms and even slow the disease process in certain cases, but lack of knowledge keeps us from developing cures,” said Noble, principal investigator for the grant. “That is why research is so critical.”

The grant builds on a dozen years of pioneering work by Noble and his collaborators that has received previous NIH funding. The work focuses on fibrosis-;an invasive overgrowth of fibrous, connective tissue that is involved in both of these lung disorders. In prior studies, the scientists pinpointed defective progenitor cells as key drivers of idiopathic pulmonary fibrosis, identified two drugs that slowed disease progression and discovered certain molecular mechanisms behind fibrosis. They also explored the role of aberrant “crosstalk” between cells in chronic lung allograft dysfunction.

The grant will fund three projects:

  • Project 1: immune checkpoint inhibitors. These proteins, secreted by cancer cells to prevent immune cells from detecting them, are found at high levels on invasive fibroblasts-;cells in the fibrous connective tissue-;of patients who have idiopathic pulmonary fibrosis or have undergone lung transplants, said Noble, who is leading this project at Cedars-Sinai. “These tissue cells are behaving like cancer cells, raising the possibility that existing anti-cancer drugs may be useful in treating these conditions,” he added.
  • Project 2: epithelial progenitor cells in idiopathic pulmonary fibrosis. These cells help maintain the lining of the lung’s airways and air sacs to allow exchange of oxygen and carbon dioxide between the air and blood during breathing. Prior studies by the team found that these cells are defective in patients with idiopathic pulmonary fibrosis, helping to explain the progressive scarring and associated loss of lung function. The new project explores the role of altered signaling by p53-;a protein that helps control the activity of progenitor cells and also prevent cancer-;in this defective process. The principal investigator for this project is Barry Stripp, PhD, professor of Medicine and Biomedical Sciences and director of lung stem cell research at Cedars-Sinai.
  • Project 3: epithelial progenitor cells in chronic lung allograft dysfunction. This project applies some of the processes in Project 2 to lung transplant failure. The hypothesis is that the status of the lung’s reserves of epithelial progenitor cells influences how well the immune system responds to various injuries to the lung, including the trauma of transplantation. The principal investigator for this project is John Belperio, MD, professor of Pulmonary and Critical Care Medicine at the David Geffen School of Medicine at UCLA.

“This prestigious National Institutes of Health grant recognizes the investigators’ significant progress in uncovering the causes of two mysterious, destructive lung conditions,” said Shlomo Melmed, MB, ChB, executive vice president and dean of the Faculty at Cedars-Sinai. “The new funding will help Cedars-Sinai, an internationally recognized leader in lung fibrosis research, continue to expand the frontiers of knowledge in pulmonary medicine.”

Source:

https://www.cedars-sinai.org/

Posted in: Medical Research News | Medical Condition News

Tags: Blood, Cancer, Cell, Critical Care, Drugs, Fibrosis, Heart, Idiopathic Pulmonary Fibrosis, Immune System, Lung Transplant, Lungs, oxygen, Protein, Pulmonary Fibrosis, Research, Stem Cell, Transplant, Trauma

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