Brant Isakson of the Robert M. Berne Cardiovascular Research Center (CVRC) Awarded 3.5 Million R01 studying role of endothelium in sepsis

Brant Isakson, PhD – Professor of Molecular Physiology and Biological Physics and the Robert M. Berne Cardiovascular Research Center

Sepsis accounts for more hospital deaths per year than any other condition in the United States, and the disease is currently devoid of any targeted pharmacological intervention. Critical to understanding how inflammation affects vascular barrier function is that endothelial cells throughout the circulatory system are not homogenous. Inflammation specifically affects vascular permeability through effects on the venous endothelium. Thus, a mechanistic view of how venous endothelial barrier function is regulated is essential.  Our current understanding of vascular barrier function does not account for endothelial heterogeneity and the unique cell adhesion and signaling pathways specific to each endothelial cell type. Purinergic signaling has been identified as a key regulator of endothelial permeability; however the cellular pathway allowing for simultaneous regulation of the purine response and tight junctions has not been explored in detail. Our work will focus on the role of the purine-release channel Pannexin 1 in venous endothelium and potentially new pharmacological interventions for treating sepsis.