NHLBI awards $13M to study inflammation in COPD, lung diseases

Projects to focus on impact of endothelium on immune system

Joana Vindeirinho, PhD avatar

by Joana Vindeirinho, PhD |

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The National Heart, Lung, and Blood Institute (NHLBI) has awarded $13 million for research focused on the link between the lung endothelium — a thin layer of cells, called endothelial cells, lining the inside of blood vessels in the lungs — and inflammation in lung diseases, including chronic obstructive pulmonary disorder (COPD).

The award will fund a team of scientists at the University of Illinois Chicago (UIC), and is part of the NHLBI’s Program Project Grants. These aim to foster collaborative study for a more effective use of resources and research synergy.

Various projects studying the role of the lung endothelium in regulating the immune system will receive funding — with a goal of finding research opportunities that might lead to new therapies for diseases that are affected by dysregulated immune responses.

“It is now becoming increasingly clear that the lung endothelium is a complex monolayer, an organ itself,” Dolly Mehta, PhD, UIC professor and interim head of the department of pharmacology and regenerative medicine at the UIC College of Medicine, said in a university press release.

“Studying this enigmatic immune regulatory function of lung endothelium is crucial for understanding how endothelial cells control immunity and defensive function of the lungs,” said Mehta, who also is the program director for the grant.

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Investigating the mechanisms of lung inflammation

Lung endothelial cells are specialized cells that are not only involved in the exchange of gases between blood and lungs, but also are important in defending the lungs against trauma and infections.

Studies have linked endothelial cell dysfunction and injury with COPD. Grant researchers believe that the unique characteristics of these cells might play a role in the chronic inflammatory conditions that are a hallmark of COPD and other lung diseases.

“We know that in tissues like those found in the lung, … the blood vessels present a unique and complicated immune environment, and we know that there is an interconnectedness between all the many cellular processes,” Mehta said.

The idea of this multi-project grant is to help create an infrastructure for collaboration among researchers looking at these various mechanisms.

The UIC research team is leading three separate projects exploring the role of the lung endothelium in controlling the lungs’ immune mechanisms and defenses.

Mehta will lead a project, awarded $2.2 million, to study a protein receptor called sphingosine 1 phosphate receptor 1 in lung endothelial cells that can promote lung integrity, which might have the potential to prevent inflammatory damage to lung blood vessels.

A second project given $1.8 million will study an enzyme called E3 ligase, and the genes that activate it, which can modulate the integrity of blood vessels’ lining. This project will be led by Asrar Malik, PhD, a professor of pharmacology and regenerative medicine.

One other project, also awarded $2.2 million, will investigate how mitochondria in endothelial cells can be used to prevent inflammatory processes from spiraling out of control. Mitochondria are small cell compartments that are responsible for energy production. Jalees Rehman, MD, also a professor and the head of the department of biochemistry and molecular genetics, will lead that project.

“The idea of this multi-project grant is to help create an infrastructure for collaboration among researchers looking at these various mechanisms,” Mehta said.

Besides these projects, the grant will also support three scientific core units, which provide necessary equipment and technical resources to the projects.

Konstantinos Chronis, PhD, will lead one of the cores that will focus on epigenetics, or how behavior and the environment affect how genes work, and transcriptomics, which is the study of the molecules produced after a gene is read at a given time. A second core, led by Gary Mo, PhD, will provide cellular imaging resources. The third core, led by Yoshikazu Tsukasaki, PhD, will provide intravital imaging, or microscopy done in living animals, and physiology resources.