Gregory Vercellotti Lab

For over 40 years at the University of Minnesota, Dr. Vercellotti has focused on studies of inflammation, oxidative stress, vascular biology, atherosclerosis, and sickle cell disease (SCD). His laboratory pioneered investigations of how the vasculature can adapt to oxidative stress and hemoglobin/heme by inducing cellular cytoprotectants including heme oxygenase-1, carbon monoxide, and ferritin. Using transgenic sickle mice, innovative models to study vaso-occlusion, and novel gene therapy techniques, his laboratory defined the pathologic role of hemolysis in vaso-occulsion and established the paramount importance of dealing with hemolysis by detoxifying heme with heme oxygenase and the anti-inflammatory properties of carbon monoxide. His lab has developed a robust and reproducible dorsal skin-fold chamber method that measures vaso-occlusion in sickle mice and allows the in vivo testing of drugs affecting vaso-occlusion. He and colleagues have previously used gene therapy with Sleeping Beauty transposons to overexpress heme oxygenase-1, the heme binding protein hemopexin, and the iron-binding protein heavy chain ferritin in the livers of SCD mice, as well as erythroid-specific expression of non-sickling adult beta-globin in primary CD34+ cells. Recent work has shown that heme released from sickle RBCs interacts with the innate immune toll-like receptor 4 (TLR4) on endothelium and blood cells to activate pro-inflammatory signaling in SCD. Current work is focused on discovering novel therapeutic approaches to modulate TLR4 signaling with targeted inhibitors.

Collaboration Vecellotti and Belcher labs since 1990's