Dr. Duo Zhang, Associate Professor in the Clinical and Administrative Pharmacy Department at the College of Pharmacy’s extended campus in Augusta, is the principal investigator of a new $2.8 million National Institutes of Health grant, awarded in August.  Dr. Somanath Shenoy, Professor and CAP Assistant Department Head for Research and Graduate Education, and Dr. Xiaoyun Wang, Limited-term Assistant Research Scientist in CAP, are serving as co-investigators on the project. The award is a remarkable career achievement—it is Dr. Zhang’s first NIH R01 grant.

Titled “Long Noncoding RNA Regulation in Complement-Mediated Endothelial Barrier Disruption: From Mechanism to Therapy,” the grant will allow Dr. Zhang and his team to investigate a newly identified RNA pathway that promotes injury to the lungs during severe bacterial pneumonia.  Subsequently, the team will develop a therapy that has the potential to lead to innovative treatments that will reduce lung injury, improve recovery, and save lives.

“I am truly honored and excited to receive this NIH R01 award,” said Dr. Zhang. “This achievement would not have been possible without the collaborative research environment at the College of Pharmacy and CAP Department. I especially express my sincere gratitude to Dr. Shenoy for his mentorship, encouragement, and steadfast support throughout the proposal development and submission process. His leadership and commitment to fostering research excellence has made a difference.”

The following are the summaries of the project that Dr. Zhang included in his grant proposal.

Public Health Relevance Statement

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe and often fatal lung conditions that affect critically ill patients, yet there are currently no effective drug therapies that directly improve survival. This project will investigate a newly identified long noncoding RNA pathway that promotes injury to the lung blood vessel barrier during severe bacterial pneumonia. By uncovering how this pathway regulates complement-mediated endothelial cell damage and by developing a targeted extracellular vesicle-based therapy to restore protective CD59 function, this research has the potential to lead to innovative treatments that reduce lung injury, improve recovery, and save lives in patients with ALI/ARDS.

Lay/Public Summary 

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious lung diseases that can develop after severe infections such as pneumonia. These conditions cause leakage of fluid into the lungs, making it difficult for patients to breathe and often requiring intensive care. Despite decades of research, there are still no effective medications that specifically treat the underlying causes of ARDS.

Our research focuses on understanding why cells that line the lung blood vessels become damaged during severe bacterial infections. We have identified a previously unknown molecule, called Lncenc1, that becomes highly active in the lungs after infection. Our preliminary studies show that removing Lncenc1 protects mice from severe lung injury and reduces fluid buildup in the lungs.

We discovered that Lncenc1 controls the expression of CD59, a natural protective protein that prevents excessive activation of the complement system, an important part of the body’s immune defense. When CD59 levels are reduced, harmful immune complexes called membrane attack complexes (MACs) can damage endothelial cells, weaken the lung barrier, and worsen lung injury.

This project will determine how Lncenc1 regulates CD59 and complement-mediated endothelial cell death during bacterial pneumonia. We will also develop a novel targeted therapy using engineered extracellular vesicles, which are naturally occurring nanoparticles capable of delivering therapeutic proteins directly to lung endothelial cells. By delivering CD59 to injured lungs, we aim to restore barrier function, reduce lung damage, and improve survival.

The knowledge gained from this study may identify new therapeutic targets and provide the foundation for innovative treatments for ALI and ARDS, ultimately improving outcomes for patients suffering from severe lung infections and respiratory failure.