The human body is estimated to remove more than 200 billion dead cells every day.
Phagocytes ingest multiple targets in succession and defective clearance of apoptotic cell results in accumulation of apoptotic cell debris, causing severe tissue injuries and has been linked with various inflammatory diseases and autoimmunity.
Research Focuses
The Role of Efferocytosis in Acute Kidney Injury
Acute kidney injury (AKI) is associated with high mortality, morbidity, and the risk of chronic kidney disease. Despite its prevalence, effective treatments remain elusive due to a lack of understanding of AKI's pathophysiology and limited data from animal models. This project investigates the potential of boosting apoptotic cell clearance as a new therapeutic direction for AKI. Utilizing our novel "Super-engulfer" mouse model, which demonstrates a significant increase in apoptotic cell uptake, we aim to determine if enhanced efferocytosis can mitigate AKI. Our "Super-engulfer" mouse model shows up to a fivefold increase in apoptotic cell clearance compared to normal mice. Additionally, we are conducting drug screenings to identify efferocytosis boosters for potential use in AKI treatment. We have identified several promising drug candidates that enhance efferocytosis. Our lab's research has shown that enhancing efferocytosis significantly reduces inflammation and promotes tissue regeneration in AKI models.
Enhancing efferocytosis in AKI could lead to novel therapeutic strategies that improve patient outcomes and reduce the long-term impact of kidney injury. This research aligns with the School of Medicine’s mission to advance healthcare through innovative research and provide evidence-based treatments. By identifying and developing new treatments for AKI, we contribute to the broader goal of improving patient care and reducing the burden of kidney diseases, ultimately enhancing the quality of life for affected individuals. This research not only promises to fill critical gaps in AKI treatment but also serves as a model for developing efferocytosis-based therapies for other inflammatory and degenerative diseases, thereby broadening the scope of clinical applications and improving overall healthcare outcomes.
The Effect of Modifying Efferocytosis in Health and Disease
Utilizing the ‘super-engulfer’ transgenic mice and other mouse models that we developed, we seek to address whether boosting apoptotic cell clearance has beneficial effects on human health. The expression of the hyperactive PS receptor showed a dramatic increase in phagocytic ability in vivo. Defective clearance of apoptotic cells can result in the accumulation of apoptotic cell debris, causing severe tissue injuries and inflammation leading to various diseases such as autoimmune disease. It is therefore vital to find novel ways (boosting dead cell clearance) to ameliorate various diseases.