Greg Vercellotti

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Credentials

MD, FACP

Bio

Administrator Info
Name: Linsey Roschen
Email: rosch053@umn.edu

Summary
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.

Research Summary

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.

Teaching Summary

Dr. Vercellotti's entire career has been focused on education. Multiple undergraduate, graduate, and, postdoctoral students, as well as residents and fellows, have rotated in his laboratory and have become faculty members at prestigious medical centers around the world. His love of education and mentoring is reflected by his experiences in directing internal medicine clerkships, directing the 2nd year hematology blood course, developing objectives with colleagues of the American Society for Hematology for all medical schools for 2nd year medical school blood courses, and serving for 7 years as Senior Associate Dean for Education, overseeing all aspects of medical education, ranging from admissions, curriculum, MD/PhD program, Graduate Medical Education, Continuing Medical Education, Allied Health, and programs to advance diversity in our health care profession. He has overseen the T32 grant for training in Hematology since 2010, developed new curriculum for Responsible Conduct of Research, and grant writing skills for future scientists. The training grant in hematology for 45 years has trained national and international leaders in hematology. Today the program continues to successfully prepare physicians and scientists for research careers as evidenced by the high percentage of T32 trainees that are academic or industry scientists. He has been involved in the MSTP and PSTP programs since their inception. 

Clinical Summary

Sickle Cell Disease, Thalassemia, Hemochromatosis, Iron-related disease, Porphyria, Anemia, White Blood Cell Disorders, Blood and Marrow Transplantation and Immunodeficiency