Hrishikesh Kulkarni, M.D.
Washington University in St. Louis
Supported by the Mary Fuller Russell Research Fund
Maintaining airway epithelial cell survival and host defense in severe pneumonia
Pneumonia is a main cause of death in the US even with antibiotics. Sic of every 100 hospital admissions are for pneumonia. Severe pneumonia causes acute respiratory distress syndrome (ARDS), which kills 33% of patients. Novel treatments for pneumonia and ARDS are urgently needed. Our group studies the complement system, which are blood proteins that respond to an infection and kill bacteria. We recently showed that many cells contain complement protein C3, including lung epithelial cells. We identified a novel role for C3 in protecting lung epithelial cells from death. Here, we will determine how C3 protects these cells from dying, and develop strategies for increasing intracellular C3 levels to reduce cell death. Subsequently, we will infect mice with Pseudomonas, which causes severe pneumonia, and determine how locally generated C3 in the lung reduces the severity of pneumonia-induced lung damage. Our long-term goal is to modulate C3 as a novel therapy to reduce pneumonia severity.
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