Greg Vercellotti, MD, FACP

Dr. Vercellotti's research focuses on inflammation and endothelial cell biology, the role of inflammation in vaso-occlusion in sickle cell anemia, the role of infection in atherosclerosis and vascular disease, and oxidative stress and vascular disease. His clinical interests range from coagulation and bleeding disorders, platelet disorders, red cell disorders, porphyria, bone marrow transplant, leukemia, lymphoma, and myeloma to immunologic deficiencies.Dr. Vercellotti's lab demonstrated that the abundant physiological iron contained in heme, is a powerful catalyst for LDL oxidation which could activate and damage endothelial cells. Heme readily enters cell membranes and the endothelium becomes hyper- susceptible to oxidant-mediated cytolysis. They demonstrated how the vasculature defends itself against heme mediated injury by the induction of the cellular cytoprotectants, heme oxygenase-1 (HO-1) and ferritin, leading to resistance to oxidant-mediated injury. They showed in vivo relevance of this cytoprotection in a variety of models from rhabdomyolysis to sickle cell disease (SCD). His lab provided significant evidence for the important role of inflammation in vaso-occlusion in SCD. They demonstrated that decreasing inflammation or decreasing reactive oxygen species, inhibiting adhesion molecules, all decrease vaso-occlusion in murine models of sickle cell disease using a unique physiological model. Due to hemolysis, both human SCD and murine SCD model have increased HO-1. They demonstrated that HO-1, when overexpressed in sickle animals, prevents hypoxia induced vaso-occlusion. Furthermore, the products of HO-1, biliverdin and CO could also modulate vaso-occlusion.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 vaso-occlusion with targeted inhibitors of TLR4, complement and BACH1. He is also collaborating on developing gene therapies and gene editing for sickle cell disease. He is a co-investigator on clinical trials for gene therapy for sickle cell disease and pi for trials for gene editing for thalassemia.