The program project, "Cytoskeletal Regulation of Lung Endothelial Pathobiology," is supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under award number P01HL126609.
Cutting-edge research investigating the genetic basis for devastating disorders in the critically ill — acute respiratory distress syndrome and ventilator-induced lung injury — will receive a major boost thanks to an $11.4 million, five-year program project grant.
The prestigious program project award from the National Heart, Lung and Blood Institute of the National Institutes of Health has been awarded to researchers at the University of Arizona Health Sciences and is led by Dr. Joe G.N. "Skip" Garcia, the UA's senior vice president for health sciences, the Dr. Merlin K. DuVal Professor of Medicine and an elected member of the National Academy of Medicine.
"I am so very pleased that Dr. Skip Garcia and his team have been awarded this grant from the NIH," said UA President Ann Weaver Hart.
"The UA and Arizona are fortunate to have a research leader of Dr. Garcia's caliber driving an effort to better understand devastating lung conditions in the critically ill," Hart said. "Coming shortly after the announcement of the largest NIH grant ever awarded in the state of Arizona, this award is another reminder of the strength of the UA Health Sciences and the impact our faculty researchers, clinicians and teachers are creating in our state and around the world."
The announcement comes after news on July 6 that UA Health Sciences and Banner Health were awarded a five-year, $43.3 million grant from the NIH to participate in the Precision Medicine Initiative Cohort Program, further expanding the impact of research and innovation at the UA.
The National Heart, Lung and Blood Institute grant will address concerns associated with acute respiratory distress syndrome, or ARDS, a rapidly progressive disease that occurs in critically ill patients affecting more than 200,000 patients in the United States with mortality ranging from 30 to 50 percent.
Patients with significant trauma, gastric acid aspiration and severe pneumonia or sepsis (a blood infection) are commonly at risk for acute respiratory distress syndrome. However, it is not clear why some patients at risk develop acute respiratory distress syndrome and ventilator-induced lung injury whereas others do not.
Key to the elevated mortality in acute respiratory distress syndrome is the profound inflammation-associated leakiness of the lung's blood vessels that results in flooding of the lungs and respiratory failure. This mandates the need for life-saving mechanical ventilation to support the patient.
Unfortunately, the mechanical stress produced by the ventilator also is a stimulus for inflammation (ventilator-induced lung injury, or VILI), and is a significant contributor to poor outcomes in acute respiratory distress syndrome.
"Throughout my career, as a pulmonologist in the intensive care unit, I observed firsthand the unacceptable mortality rates that occur in the critically ill with ARDS, particularly in patients of color. I realized the necessity to develop greater insights into the mechanisms for development of ARDS and VILI and to identify novel therapeutics for this huge unmet medical need. Our program project team is designed to do just that," said Garcia, who has been conducting research in this area for more than three decades.
"We have sequenced a number of key genes involved in risk for ARDS and VILI and have a better understanding of genetic variants in African-Americans and Latinos who are at increased risk for developing ARDS and succumbing to the disease," he said. "This study will advance a more personalized medicine approach to ARDS and VILI, giving physicians the ability to incorporate the genetic basis behind susceptibility into their medical decision-making as well as potentially offering new ARDS therapeutics that are based on our research."
Mechanical ventilation supports patients with acute respiratory distress syndrome but can cause ventilator-induced lung injury, a contributor to poor outcomes in acute respiratory distress syndrome.
"ARDS is life threatening and occurs in our most vulnerable patients in the intensive care unit, yet there remains no specific treatment for this condition. This grant will allow the Garcia lab, the leading scientific authority worldwide in the field of ARDS, to predict who will get ARDS and to bring novel therapies to patients with this devastating syndrome," said Dr. Ken Knox, chief of the UA Division of Pulmonary, Adult Allergy, Critical Care and Sleep Medicine, and professor of medicine in the UA Department of Medicine.
Program Project Grants, or PPGs, are among the most highly competitive, scientifically peer-reviewed funding mechanisms awarded by the National Institutes of Health, funding collaborative research programs in differing areas of expertise to achieve results not attainable by investigators working independently.
Joining Garcia on the UAHS PPG is Anne E. Cress, deputy dean for research affairs and professor of cellular and molecular medicine and radiation oncology at the UA College of Medicine – Tucson.
"It is an exciting opportunity to work with the assembled research team on the UAHS PPG led by Dr. Garcia," Cress said. "PPGs are critical for spawning innovative basic research that impacts patient care, and very few exist across the UA. We are fortunate to have his leadership and vision to choose the PPG mechanism to build our research portfolio in the health sciences."