Jorn Karhausen, MD
The American Heart Association’s Research Committee has awarded Duke Anesthesiology’s Jorn Karhausen, MD, the 2019 Innovative Project Award ($200,000 in funding over two years) for his study titled, “Enhanced Neutrophil SUMOylation as a key to Anti-Inflammatory Effects of Hypothermia.”
One of the few strategies shown to modulate inflammation resulting from ischemia and reperfusion is hypothermia, and therefore patients are often cooled (e.g. after cardiac arrest or during cardiac surgery). However, adverse effects on coagulation and host-defense systems, and inconsistent results in clinical trials, highlight persistent problems with this approach.
Wei Yang, PhD
With this project, Karhausen (principal investigator) and Dr. Wei Yang (co-investigator) aim to elucidate the underlying mechanisms that link low temperature to inflammation control. Their ongoing work suggests that hypothermia activates endogenous stress response programs, such as the SUMOylation network. Posttranslational modification with Small Ubiquitin-like MOdifiers (SUMO) is highly dynamic, and because transcription factors are key targets, significant changes in protein SUMOylation can achieve rapid reprograming of entire pathways. Their work will consequently focus on neutrophils as a primary effector cell of ischemia/reperfusion injury and will use a broad spectrum of techniques, including cell-permeable inhibitory peptides and conditional genetic approaches, to define the specific SUMOylation effects in this cell population. By cross referencing results with observations made in patients undergoing deep hypothermic circulatory arrest, Karhausen and Yang aim to validate their experimental findings and open translational extensions for future projects.