Lung Repair by Tetraspanin Interacting Protein IGSF3
Abstract
Objectives and Rationale: A large number of military, their family, and Veterans are smokers or ex-smokers. Some develop relentless destruction of their lungs called emphysema, or other conditions such as asthma, lung cancer, chronic bronchitis, even after they stop smoking. Understanding how some lungs resist the same amount of smoking, whereas other lungs fail is important to determine the risk and treatments of smoking-related lung disease. Moreover, smoking predisposes to other acute diseases, such as pneumonias or acute lung failure from a two-hit injury, and many people are unable to stop smoking. Enforcing their lungs may prevent such terrible outcomes. The lung is extremely versatile in repairing lung injury, with people recovering almost normal lung function after severe pneumonias or COVID-19 that initially placed them on a ventilator. We will study the failure of repair of lung injury induced by inhalation of toxicants such as smoking as a major risk and cause for developing chronic lung diseases such as emphysema. We discovered a new protein that can help zip cells together so they can more readily withstand stress and breaches induced by smoking. This protein, called IGSF3 (immunoglobulin superfamily), is strategically positioned to not only form a good barrier, but also to help move cells to fix the breaches in the barrier if they had formed. Using research models that allow us to make sure that the results will be quickly applicable to humans and are not only confined laboratory models, we are uniquely positioned at National Jewish Health, a top respiratory hospital in the world, to address this new idea. Our research group has the experience and the tools at hand to succeed in their research. In fact, our research idea came from the Principal Investigator examining in clinic a young woman who had stopped smoking and she still had galloping emphysema that made her doctors refer her to lung transplantation. By chance, we found that she had a genetic mutation that made her unable to produce the IGSF3 protein. However, nobody had published anything about this protein at that time. But the striking finding and the fact that this protein belonged to a family of molecules that served a role to secure barriers gave us the rationale and impetus to develop this proposal. Relevance to FY21 PRMRP Topic Areas: This project addresses identified gaps and research priorities for the PRMRP. We will develop preventive strategies to optimize respiratory health of our military personnel including studies, and long term will inform on mechanism of lung resilience and repair following exposure to other respiratory inhalants such as those occurring following burn pit exposure and adverse health events related to military deployment to Iraq and Afghanistan and exposure to airborne hazards to ascertain toxicity of natural dust and burn pit combustion product, and will impact knowledge on the cause, treatment, and prevention of constrictive bronchiolitis, asthma, and other chronic lung diseases. Applicability and Impact of Research: The application aligns with the vision of to improve the health, care, and well-being of all military Service Members, Veterans, and beneficiaries, with direct relevance to military respiratory health. Using our unique human samples coupled with state-of-the-art technologies, our proposal will advance the knowledge of the mechanisms of maintenance of lung repair of injury. To our knowledge, for the first time, our studies will define the role of IGSF3 as a resilience factor in chronic obstructive pulmonary diseases (COPD). This study will have potential therapeutic and prognosis applicability to many lung diseases, including emphysema/COPD and therefore will generate approaches to improve the respiratory health of military personnel and their family members.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210255
Entities
People
- Irina Petrache
Organizations
- National Jewish Health
- United States Army