A new research program at the University of Louisville will focus on developing better methods for studying lung inflammation and allow for new research into causes and potential therapies for lung diseases that affect millions of Americans. Thanks to a pledge of $1.05 million over five years from the GSG III Foundation, Inc., the UofL School of Medicine will create the Gibbs Lung Research Program at the Cardiovascular Innovation Institute (CII). The program will use established research and existing partnerships at CII to develop improved methods for studying diseased lungs and to explore new treatments for inflammatory lung disease.

“Given the number of people in Louisville and Kentucky who suffer from lung diseases, from COPD to cystic fibrosis to asthma, we are happy to support the community by creating a program that can ultimately lead to life-changing therapies for the people of Louisville and across the United States,” said George Gibbs, chair of the GSG III Foundation, which is based in Louisville.

Lung disease is the third leading cause of death in the United States, with chronic obstructive pulmonary disease (COPD) alone affecting 13.5 million people. Inflammation of the lungs is often the first sign of more serious lung disease. However, scientists have limited methods for studying inflammation in lungs to better understand how and why it occurs and to develop treatments.

“Other than lung cancer, most people do not understand the extent of the problem of lung disease,” said Laman Gray Jr., M.D., executive and medical director of the CII. “Inflammatory lung diseases are debilitating and affect millions of individuals. What is worse is the scientific world has limited capabilities for studying these diseases. This gift from the GSG III Foundation will allow us to develop expanded modeling opportunities with the goal of reducing human suffering from lung disease.”

More than 70 percent of donor lungs are unusable for transplant. Support from University of Louisville Hospital and Jewish Hospital, both part of KentuckyOne Health, will enable the program’s investigators to obtain donated human lungs that cannot be used for transplant. Researchers in the new program plan to develop techniques to sustain these donor lungs over a longer period of time, allowing them to study the causes of inflammation as well as test potential therapies.

The goals for the program are three-part:

-Establish an ex vivo human lung model allowing lungs that are unsuitable for transplant to be brought to CII for research. The donated lungs will be enclosed in a sterile plastic dome, attached to a ventilator, pump and filters. The lungs will be maintained at normal body temperature and treated with a bloodless solution containing nutrients, proteins and oxygen.

-Develop methods for long-term support of the ex vivo lungs. Current processes enable the lungs to be supported for up to 12 hours, which is long enough to transport them for transplant, but not long enough for meaningful study.

-Once these techniques are in place, researchers in the program intend to use the research models explore areas of potential benefit, including:

• Cell therapy – Explore the use of stem and regenerative cells isolated from a patient’s own fat tissue to treat lung inflammation.
• Mechanics – Develop improved methods of respiratory support by studying the biomechanics of diseased lungs and the benefits of ex-vivo lung perfusion, a method of strengthening lungs outside the body.
• Gene expression - Understand the course of dysfunction and dysregulation among the more than 40 different cell types within the lung and profile the functional changes that occur in diseased lungs and compare the gene expression to healthy lungs.

The program’s investigators will include Gray, James B. Hoying, Ph.D., division chief, cardiovascular therapeutics, Stuart K. Williams, Ph.D., division chief, bioficial organs, George Pantalos, Ph.D., professor of surgery and bioengineering, Victor van Berkel, M.D., cardiovascular and thoracic surgeon, and Shizuka Uchida, Ph.D., associate professor of medicine, all of UofL.

UofL researchers hope the Gibbs Lung Research Program ultimately will become a comprehensive lung research program, leading to valuable treatments that will slow or reverse the course of lung disease, improving quality of life for millions of people.

About the Cardiovascular Innovation Institute

Since opening in 2007, the Cardiovascular Innovation Institute has focused on the discovery, development and implementation of innovative treatments for cardiovascular disease. The CII’s main goal is to foster a world-class collaborative, integrated, multi-disciplinary enterprise encompassing basic, translational, clinical and population research in cardiovascular disease, affecting individuals throughout their entire lifespan, from prenatal life to death. The CII is a partnership effort of the University of Louisville and the Jewish Heritage Fund for Excellence.