MICaB Graduate Program
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Gregory M. Vercellotti, M.D
Department of Medicine
University of Illinois, Chicago, 1976, M.D.
Vascular Biology, Inflammation, Atherosclerosis, Sickle Cell Anemia
For 30+ years at the University of Minnesota I have been involved in research, teaching and patient care. I have focused on understanding the interactions of inflammation, oxidative stress and vascular biology which underpin a variety of disease states from atherosclerosis to sickle cell disease (SCD). Our 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. We 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. We showed in vivo relevance of this cytoprotection in a variety of models from rhabdomyolysis to sickle cell disease (SCD). Our lab provided significant evidence for the important role of inflammation in vaso-occlusion in SCD. We 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. We 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.
Selected Recent Publications:
- Belcher JD, Young M, Chen C, Nguyen J, Burhop K, Tran P, Vercellotti GM. 2013. MP4CO, a pegylated hemoglobin saturated with carbon monoxide is a modulator of HO-1, inflammation and vaso-occlusion in transgenic sickle mice. Blood. Aug 1. [Epub ahead of print]
- Schaer DJ, Buelher PW, Alayash AI, Belcher JD and Vercellotti, GM.2013. Hemolysis and Free Hemoglobin Revisited: Exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood 121(8):1276-1284.
- Vercellotti GM, Moldow CF, Jacob HS. 2012. Complement, oxidants, and endothelial injury: how a bedside observation opened a door to vascular biology. Journal of Clinical Investigation, J Clin Invest. Sep 4;122(9):3044-5.
- Beckman JD, Chen C, Nguyen J , Thayanithy V, Subramanian S, Steer CJ, and Vercellotti GM. 2011. Regulation of heme oxygenase-1 protein expression by miR-377 in combination with mir-217. J Biol Chem. Feb 4;286(5):3194-202.
- Sjeklocha LM, Park CW, Wong P Y-P, Roney MK, Belcher JD, Kaufman DS, Vercellotti GM, Hebbel RP, Steer CJ. 2011. Erythroid-specific expression of b-globin from Sleeping Beauty-transduced hematopoietic progenitors. PLoS One 6:e29110.
- Belcher JD, Vineyard JV, Bruzzone CM, Chen C, Beckman JD, Nguyen J, Steer C, and Vercellotti GM. 2010. Heme Oxygenase-1 Gene Therapy in a Murine Model of Sickle Cell Disease. J Molecular Medicine. Jul;88(7):665-75.
- Beckman JD, Belcher JD, Vineyard JV, Chen C,Nguyen J, Nwaneri MO, O’Sullivan MG, Gulbahce E, Hebbel RP, Vercellotti GM. 2009. Inhaled Carbon Monoxide Reduces Leukocytosis in a Murine Model of Sickle Cell Disease. Am J Physiol Heart Circ Physiol. Oct;297(4):H1243-53.