Robert P. Hebbel, M.D.

Robert P. Hebbel, M.D., holds the George Clark Professorship in the Department of Medicine. He received the MD degree from the University of Minnesota in 1973 and subsequently trained in Internal Medicine (at the University of Washington, Seattle) and hematology (at the University of Minnesota). Dr. Hebbel is a member of the Cancer Center, the Biomedical Engineering Institute, and the Lillehei Heart Institute.

Dr. Hebbel's research interests include: the vascular pathobiology of sickle disease; endothelial cell signal transduction and cell cycle in angiogenesis; developmental biology of the vascular system; and novel, endothelial-based gene therapy approaches to hemophilia and cancer.

Selected Publications

Ney PA, Christopher MM, Hebbel RP: Synergistic effects of oxidation and deformation upon erythrocyte monovalent cation leak. Blood 75:1192-1198, 1990

Sugihara T, Rawicz W, Evans EA, Hebbel RP: Lipid hydroperoxides permit deformation-dependent leak of monovalent cation from erythrocytes. Blood 77:2757-2763, 1991

Hebbel RP, Mohandas N: Reversible deformation-dependent RBC cation leak: Extreme sensitivity conferred by minimal peroxidation. Biophysical Journal 60:712-715, 1991

Sugihara T, Hebbel RP: Exaggerated cation leak from oxygenated sickle RBC during deformation: Evidence for a unique leak pathway. Blood 80:2374-2378, 1992

Sugihara K, Sugihara T, Mohandas N, Hebbel RP: Thrombospondin mediates adherence of CD36-positive sickle reticulocytes to endothelial cells. Blood 80:2634-2642, 1992

Sugihara T, Repka T, Hebbel RP: Detection, characterization, and bioavailability of membrane-associated iron in the intact sickle red cell. J Clin Invest 90:2327-2322, 1992

Sugihara T, Yawata Y, Hebbel RP: Deformation of swollen erythrocytes provides a model of sickling induced leak pathways, including a novel bromide sensitive component. Blood 83:2684-2691, 1994.

Shalev O, Repka T, Goldfarb A, Grinberg L, Abrahamov A, Olivieri NF, Rachmilewitz EA, Hebbel RP: Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle RBC both in vitro and in vivo. Blood 86:2008-2013, 1995.

Gupta K, Ramakrishnan S, Browne PV, Solovey A, Hebbel RP: A novel technique for culture of human dermal microvascular endothelial cells in either serum-free or serum-supplemented conditions: Isolation by panning and stimulation with vascular endothelial growth factor. Experimental Cell Research 230:244-251, 1997.

Browne PV, Shalev O, Kuypers FA, Brugnara C, Solovey A, Mohandas N, Schrier SL, Hebbel RP: Removal of erythrocyte membrane iron in vivo ameliorates the pathobiology of murine thalassemia. JCI 100:1459-64, 1997.

Solovey A, Lin Y, Browne P, Choong S, Wayner E, Hebbel RP: Circulating activated endothelial cells in sickle cell anemia. New Engl J Med 337:1584-1590, 1997.

Solovey A, Gui L, Key NS, Hebbel RP: Tissue factor expression by endothelial cells in sickle cell anemia. J Clin Invest 101:1899-1904, 1998.

Gupta K, Gupta P, Solovey A, Hebbel RP: Mechanism of interaction of thrombospondin with human endothelium and inhibition of sickle erythrocyte adhesion to human endothelial cells by heparin. Biochim et Biophys Acta 1453:63-73, 1999.

Solovey A, Gui L, Ramakrishnan S, Steinberg M, Hebbel RP: Sickle cell anemia as a possible state of enhanced anti-apoptotic tone: Survival effect of VEGF on circulating and unanchored endothelial cells. Blood 93:1-8, 1999.

Gupta K, Kshirsagar S, Li W, Gui L, Ramakrishnan S, Gupta P, Law PY, Hebbel RP: VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res 247:495-504, 1999.

Belcher JD, Marker PH, Geiger P, Girotti AW, Steinberg MH, Hebbel RP, Vercellotti GM: LDL susceptibility to oxidation and cytotoxicity to endothelium in sickle cell anemia. J Lab Clin Med 133:605-612, 1999.

Gupta K, Ramakrishnan S, Kshirsagar S, Gupta P, Hebbel RP: Thrombospondin prevents the anti-apoptotic effect of VEGF and inhibits VEGF-induced human microvascular endothelial cell proliferation and angiogenesis. Angiogenesis 3:147-158, 1999.

Lin Y, Weisdorf DJ, Solovey A, Hebbel RP: Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105:71-77, 2000.

Kaul DK, Hebbel RP: Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice, but not normal mice. J Clin Invest 106:411-420, 2000.

Osarogiagbon UR, Choong S, Belcher J, Vercellotti G, Paller MS, Hebbel RP: Reperfusion injury pathophysiology in sickle transgenic mice. Blood 96:314-320, 2000.

Solovey AA, Solovey AN, Harkness J, Hebbel RP: Modulation of endothelial cell activation in sickle cell disease: A pilot study. Blood 97:1937-1941, 2001.

Solovey AN, Gui L., Chang L, Enenstein J, Browne PV, Hebbel RP: Cloning, identification and functional assessment of endothelial P1H12. J Lab Clin Med 138:322-331, 2001.

Lin Y, Chang L, Solovey A, Healey JF, Lollar P, Hebbel RP: Use of blood outgrowth endothelial cells for gene therapy of hemophilia A. Blood 99:457-462, 2002.

Gupta K, Gupta P, Wild R, Ramakrishnan S, Hebbel RP: Binding and displacement of vascular endothelial growth factor (VEGF) by thrombospondin: effect on human microvascular endothelial cell proliferation and angiogenesis. Angiogenesis 3:147-58, 1999.

Belcher JD, Bryant CJ, Nguyen J, Bowlin PR, Kielbik MC, Bischof JC, Hebbel RP, Vercellotti GM: Transgenic sickle mice have vascular inflammation. Blood 101:3953-9, 2003.

Kaul DJ, Liu XD, Choong S, Belcher JD, Vercellotti GM, Hebbel RP. Anti-inflammatory therapy ameliorates leukocyte adhesion and microvascular flow abnormalities in transgenic sickle mice.  Am J Physiol Heart Circ Physiol 2004; 287:H293-301.

Solovey A, Kollander R, Shet A, Milbauer LC, Choong S, Panoskaltsis-Mortari A, Blazar BR, Kelm RJ Jr, Hebbel RP.  Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin.  Blood 2004; 104:840-846.

Hebbel RP.  Special issue of microcirculation: Examination of the vascular pathobiology of sickle cell anemia.  Microcirculation 2004; 11:99-100.

Hebbel RP, Osarogiagbon R, Kaul D.  The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy.  Microcirculation 2004; 11:129-151.

Xia YF, Ye BQ, Li YD, Wang JG, He XJ, Lin X, Yao X, Ma D, Slungaard A, Hebbel RP, Key NS, Geng JG.  Andographolide attenuates inflammation by inhibition of NK-kappa B activation through covalent modification of reduced cysteine 62 of p50.  J Immunol 2004; 173:4207-4217.

Kalambur VS, Mahaseth H, Bischof JC, Kielbik MC, Welch TE, Vilback A, Swanlund DJ, Hebbel RP, Belcher JD, Vercellotti GM.  Microvascular blood flow and stasis in transgenic sickle mice: Utility of a dorsal skin fold chamber for intravital microscopy.  Am J Hematol 2004; 77:117-125.

Jy W, Horstman LL, Jimenez JJ, Ahn YS, Biro E, Nieuwland R, Sturk A, Dignat-George F, Sabatier F, Camoin-Jau L, Sampol J, Hugel B, Zobairi F, Freyssinet JM, Nomura S, Shet AS, Key NS, Hebbel RP.  Measuring circulating cell-derived microparticles.  J Thromb Haemost 2004; 2:1842-1843.

Shet AS, Key NS, Hebbel RP.  Measuring circulating cell-derived microparticles.  J Thromb Haemost 2004; 2:1848-1850.

Wood KC, Hebbel RP, Granger DN.  Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice.  FASEB J. 2005; 19:989-91.

Stachelek SJ, Alferiev I, Connolly JM, Sacks M, Hebbel RP, Bianco R, Levy RJ. Cholesterol-modified polyurethane valve cusps demonstrate blood outgrowth endothelial cell adhesion post-seeding in vitro and in vivo.  Ann Thorac Surg. 2006; 81:47-55.

De Meyer SF, Vanhoorelbeke K, Chuah MK, Pareyn I, Gillijns V, Hebbel RP, Collen D, Deckmyn H, Vandendriessche T.  Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor.  Blood. 2006; 107:4728-36.

Belcher JD, Mahaseth H, Welch TE, Otterbein LE, Hebbel RP, Vercellotti GM.  Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice.  J Clin Invest. 2006; 116:808-16.

Wood KC, Hebbel RP, Lefer DJ, Granger DN.  Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction.  Free Radic Biol Med. 2006; 40:1443-53.

Hebbel RP. Adhesion of sickle red cells to endothelium: myths and future directions. Transfus Clin Biol. 2008;15:14-18.