Biomedical Research Education & Training
Faculty Member

Hatzopoulos, Antonis K., Ph.D.
Associate Professor of Medicine
Associate Professor of Cell and Developmental Biology

Lab Url: N/A

Phone Number: (615) 936 5529

Email Address:

Hatzopoulos, Antonis's picture
Academic history
B.S., Aristotelion University of Thessaloniki, Thessaloniki, Greece
Ph.D., Northwestern University, Dept. of Biochemistry, Molecular Biology and Cell Biology, Evanston, IL
Postdoctoral, Max-Planck Institute of Biophysical Chemistry, Gottingen, Germany
Postdoctoral, M. I. T., Department of Biology, Cambridge, MA

Office Address   Mailing Address

MRB IV - P425C

Division of Cardiovascular Medicine MRB IV - P425C 37232-6300

Research Keywords
Regenerative medicine, embryonic stem cells, induced pluripotent stem cells, stem cell biology, development, heart, BMP, wnt, myocardial infarction, cell therapy, endothelial cells, cardiomyocytes, zebrafish, mouse,Cardiac function,Developmental biology,Gene regulation,Genomics,Heart,Molecular medicine,Mouse,Stem cells,Vascular Biology

Research Description
Our research focuses on cardiovascular progenitor cells as a model system to study heart and blood vessel development and as cell therapy tools in adult disease models. We have shown that in vitro expanded embryonic endothelial progenitor cells form blood vessels after transplantation in the developing embryo. In adult disease models, we found that vascular progenitor cells are originally recruited to sites of angiogenesis by endothelial P-selectin. In mouse models of multiple tumors, we demonstrated that the progenitor cells home to hypoxic metastases with high VEGF expression, but spare well-vascularized tumors and normal organs. Based on these findings, we used the cells as a??Trojan horsesa?? to deliver toxic agents directly to the tumor tissue killing malignant cells and blocking tumor growth. Exploring further the specific accumulation of progenitor cells to ischemic sites in vivo, we found that transplantation of progenitor cells under acute (heart) or chronic ischemia (hindlimb) enhances vascularization and improves tissue recovery. Our laboratory currently investigates the mechanisms of cardiac cell specification during embryonic stem cell differentiation and the biology of progenitor cells after ischemic injury in the adult heart. We found that canonical wnt signaling is activated during scar formation and is a critical pathway in the activation of endothelial cells and myofibroblasts after experimental myocardial infarction. We have recently discovered that the BMP antagonist PRDC is an integral component of the regulatory network that fine tunes both Bmp4 expression and signaling activity during heart development, providing novel insights into the molecular basis of congenital cardiac defects. We currently investigate the role of PRDC in cardiac repair after ischemic injury. Our laboratory is a member of the Cardiovascular Cell Therapy Research Network (CCTRN) and the Progenitor Cell Biology Consortium (PCBC), which have been established by NHLBI in 2007 and 2009, respectively.

Hecht, N, Schneider, UC, Czabanka, M, Vinci, M, Hatzopoulos, AK, Vajkoczy, P, Woitzik, J. Endothelial progenitor cells augment collateralization and hemodynamic rescue in a model of chronic cerebral ischemia. J Cereb Blood Flow Metab, 2014

M??ller, II, Melville, DB, Tanwar, V, Rybski, WM, Mukherjee, A, Shoemaker, MB, Wang, WD, Schoenhard, JA, Roden, DM, Darbar, D, Knapik, EW, Hatzopoulos, AK. Functional modeling in zebrafish demonstrates that the atrial-fibrillation-associated gene GREM2 regulates cardiac laterality, cardiomyocyte differentiation and atrial rhythm. Dis Model Mech, 6(2), 332-41, 2013

Aisagbonhi, O, Rai, M, Ryzhov, S, Atria, N, Feoktistov, I, Hatzopoulos, AK. Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition. Dis Model Mech, 4(4), 469-83, 2011 PMCID:3124051

Defresne, F, Bouzin, C, Grandjean, M, Dieu, M, Raes, M, Hatzopoulos, AK, Kupatt, C, Feron, O. Preconditioned Endothelial Progenitor Cells Reduce Formation of Melanoma Metastases through SPARC-Driven Cell-Cell Interactions and Endocytosis. Cancer Res, 71(14), 4748-4757, 2011

Gupta, MK, Walthall, JM, Venkataraman, R, Crowder, SW, Jung, DK, Yu, SS, Feaster, TK, Wang, X, Giorgio, TD, Hong, CC, Baudenbacher, FJ, Hatzopoulos, AK, Sung, HJ. Combinatorial polymer electrospun matrices promote physiologically-relevant cardiomyogenic stem cell differentiation. PLoS One, 6(12), e28935, 2011

Hammon, M, Herrmann, M, Bleiziffer, O, Pryymachuk, G, Andreoli, L, Munoz, LE, Amann, KU, Mondini, M, Gariglio, M, Air??, P, Schellerer, VS, Hatzopoulos, AK, Horch, RE, Kneser, U, St??rzl, M, Naschberger, E. Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases. J Cell Mol Med, 15(7), 1582-92, 2011 PMCID:2929864

Hao, J, Sawyer, DB, Hatzopoulos, AK, Hong, CC. Recent Progress on Chemical Biology of Pluripotent Stem Cell Self-renewal, Reprogramming and Cardiomyogenesis. Rec Pat Regen Med, 1(3), 263-274, 2011

Melville, DB, Montero-Balaguer, M, Levic, DS, Bradley, K, Smith, JR, Hatzopoulos, AK, Knapik, EW. The feelgood mutation in zebrafish dysregulates COPII-dependent secretion of select extracellular matrix proteins in skeletal morphogenesis. Dis Model Mech, 2011

Rai, M, Walthall, JM, Hu, J, Hatzopoulos, AK. Continuous antagonism by Dkk1 counter activates canonical wnt signaling and promotes cardiomyocyte differentiation of embryonic stem cells. Stem Cells Dev, 2011

Safa, RN, Peng, XY, Pentassuglia, L, Lim, CC, Lamparter, M, Silverstein, C, Walker, J, Chen, B, Geisberg, C, Hatzopoulos, AK, Sawyer, DB. Neuregulin-1I? regulation of embryonic endothelial progenitor cell survival. Am J Physiol Heart Circ Physiol, 300(4), H1311-9, 2011 PMCID:3124051

Wang, WD, Melville, DB, Montero-Balaguer, M, Hatzopoulos, AK, Knapik, EW. Tfap2a and Foxd3 regulate early steps in the development of the neural crest progenitor population. Dev Biol, 360(1), 173-85, 2011

Wu, B, Wang, Y, Lui, W, Langworthy, M, Tompkins, KL, Hatzopoulos, AK, Baldwin, HS, Zhou, B. Nfatc1 coordinates valve endocardial cell lineage development required for heart valve formation. Circ Res, 109(2), 183-92, 2011

Hinkel, R, Bock-Marquette, I, Hatzopoulos, AK, Hazopoulos, AK, Kupatt, C. Thymosin beta4: a key factor for protective effects of eEPCs in acute and chronic ischemia. Ann N Y Acad Sci, 1194, 105-11, 2010 PMCID:2921924

Pfosser, A, El-Aouni, C, Pfisterer, I, Dietz, M, Globisch, F, Stachel, G, Trenkwalder, T, Pinkenburg, O, Horstkotte, J, Hinkel, R, Sperandio, M, Hatzopoulos, AK, Boekstegers, P, Bals, R, Kupatt, C. NF kappaB activation in embryonic endothelial progenitor cells enhances neovascularization via PSGL-1 mediated recruitment: novel role for LL37. Stem Cells, 28(2), 376-85, 2010 PMCID:2810366

Ratliff, BB, Ghaly, T, Brudnicki, P, Yasuda, K, Rajdev, M, Bank, M, Mares, J, Hatzopoulos, AK, Goligorsky, MS. Endothelial progenitors encapsulated in bioartificial niches are insulated from systemic cytotoxicity and are angiogenesis competent. Am J Physiol Renal Physiol, 299(1), F178-86, 2010 PMCID:2904163

Schoenhard, JA, Hatzopoulos, AK. Stem cell therapy: pieces of the puzzle. J Cardiovasc Transl Res, 3(1), 49-60, 2010 PMCID:2810366

Schoenhard, JA, Hatzopoulos, AK. Time is like a clock in my heart: implications for stem cell delivery after myocardial infarction. Cardiology, 117(2), 158-60, 2010 PMCID:2992645

Traverse, JH, Henry, TD, Vaughan, DE, Ellis, SG, Pepine, CJ, Willerson, JT, Zhao, DX, Simpson, LM, Penn, MS, Byrne, BJ, Perin, EC, Gee, AP, Hatzopoulos, AK, McKenna, DH, Forder, JR, Taylor, DA, Cogle, CR, Baraniuk, S, Olson, RE, Jorgenson, BC, Sayre, SL, Vojvodic, RW, Gordon, DJ, Skarlatos, SI, Moy??, LA, Simari, RD, , . LateTIME: a phase-II, randomized, double-blinded, placebo-controlled, pilot trial evaluating the safety and effect of administration of bone marrow mononuclear cells 2 to 3 weeks after acute myocardial infarction. Tex Heart Inst J, 37(4), 412-20, 2010 PMCID:2929864

Willerson, JT, Perin, EC, Ellis, SG, Pepine, CJ, Henry, TD, Zhao, DX, Lai, D, Penn, MS, Byrne, BJ, Silva, G, Gee, A, Traverse, JH, Hatzopoulos, AK, Forder, JR, Martin, D, Kronenberg, M, Taylor, DA, Cogle, CR, Baraniuk, S, Westbrook, L, Sayre, SL, Vojvodic, RW, Gordon, DJ, Skarlatos, SI, Moy??, LA, Simari, RD, , . Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design. Am Heart J, 160(2), 215-23, 2010 PMCID:2921924

Yasuda, K, Park, HC, Ratliff, B, Addabbo, F, Hatzopoulos, AK, Chander, P, Goligorsky, MS. Adriamycin nephropathy: a failure of endothelial progenitor cell-induced repair. Am J Pathol, 176(4), 1685-95, 2010 PMCID:2843460

Bleiziffer, O, Horch, RE, Hammon, M, Arkudas, A, Naschberger, E, Rath, S, Pryymachuk, G, Beier, JP, Hatzopoulos, AK, St??rzl, M, Kneser, U. T17b murine embryonal endothelial progenitor cells can be induced towards both proliferation and differentiation in a fibrin matrix. J Cell Mol Med, 13(5), 926-35, 2009

Boudoulas, KD, Hatzopoulos, AK. Cardiac repair and regeneration: the Rubik''s cube of cell therapy for heart disease. Dis Model Mech, 2(7-8), 344-58, 2009

Joggerst, SJ, Hatzopoulos, AK. Stem cell therapy for cardiac repair: benefits and barriers. Expert Rev Mol Med, 11, e20, 2009

Schulz, H, Kolde, R, Adler, P, Aksoy, I, Anastassiadis, K, Bader, M, Billon, N, Boeuf, H, Bourillot, PY, Buchholz, F, Dani, C, Doss, MX, Forrester, L, Gitton, M, Henrique, D, Hescheler, J, Himmelbauer, H, H??bner, N, Karantzali, E, Kretsovali, A, Lubitz, S, Pradier, L, Rai, M, Reimand, J, Rolletschek, A, Sachinidis, A, Savatier, P, Stewart, F, Storm, MP, Trouillas, M, Vilo, J, Welham, MJ, Winkler, J, Wobus, AM, Hatzopoulos, AK, , . The FunGenES database: a genomics resource for mouse embryonic stem cell differentiation. PLoS One, 4(9), e6804, 2009 PMCID:2731164

Traverse, JH, Henry, TD, Vaughn, DE, Ellis, SG, Pepine, CJ, Willerson, JT, Zhao, DX, Piller, LB, Penn, MS, Byrne, BJ, Perin, EC, Gee, AP, Hatzopoulos, AK, McKenna, DH, Forder, JR, Taylor, DA, Cogle, CR, Olson, RE, Jorgenson, BC, Sayre, SL, Vojvodic, RW, Gordon, DJ, Skarlatos, SI, Moye'', LA, Simari, RD, , . Rationale and design for TIME: A phase II, randomized, double-blind, placebo-controlled pilot trial evaluating the safety and effect of timing of administration of bone marrow mononuclear cells after acute myocardial infarction. Am Heart J, 158(3), 356-63, 2009

Beck, H, Semisch, M, Culmsee, C, Plesnila, N, Hatzopoulos, AK. Egr-1 regulates expression of the glial scar component phosphacan in astrocytes after experimental stroke. Am J Pathol, 173(1), 77-92, 2008 PMCID:2438287

Bidzhekov, K, Hautmann, M, Semisch, M, Weber, C, Engelmann, B, Hatzopoulos, AK. Rafs constitute a nodal point in the regulation of embryonic endothelial progenitor cell growth and differentiation. J Cell Mol Med, 11(6), 1395-407, 2008

Hao, J, Daleo, MA, Murphy, CK, Yu, PB, Ho, JN, Hu, J, Peterson, RT, Hatzopoulos, AK, Hong, CC. Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS ONE, 3(8), e2904, 2008 PMCID:2483414

Hinkel, R, El-Aouni, C, Olson, T, Horstkotte, J, Mayer, S, M??ller, S, Willhauck, M, Spitzweg, C, Gildehaus, FJ, M??nzing, W, Hannappel, E, Bock-Marquette, I, DiMaio, JM, Hatzopoulos, AK, Boekstegers, P, Kupatt, C. Thymosin beta4 is an essential paracrine factor of embryonic endothelial progenitor cell-mediated cardioprotection. Circulation, 117(17), 2232-40, 2008 PMCID:2672916

Karantzal, E, Schulz, H, Hummel, O, Hubner, N, Hatzopoulos, A, Kretsovali, A. Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis. Genome Biol, 9(4), R65, 2008 PMCID:2643936

Mages, J, Freim??ller, K, Lang, R, Hatzopoulos, AK, Guggemoos, S, Koszinowski, UH, Adler, H. Proteins of the Secretory Pathway Govern Virus Productivity During Lytic Gammaherpesvirus Infection. J Cell Mol Med, 2008 PMCID:2673020

Ryzhov, S, Solenkova, NV, Goldstein, AE, Lamparter, M, Fleenor, T, Young, PP, Greelish, JP, Byrne, JG, Vaughan, DE, Biaggioni, I, Hatzopoulos, AK, Feoktistov, I. Adenosine receptor-mediated adhesion of endothelial progenitors to cardiac microvascular endothelial cells. Circ Res, 102(3), 356-63, 2008

Tsukamoto, H, Irie, A, Senju, S, Hatzopoulos, AK, Wojnowski, L, Nishimura, Y. B-Raf-mediated signaling pathway regulates T cell development. Eur J Immunol, 38(2), 518-27, 2008 PMCID:2706025

Langer, HF, May, AE, Vestweber, D, De Boer, HC, Hatzopoulos, AK, Gawaz, M. Platelet-induced differentiation of endothelial progenitor cells. Semin Thromb Hemost, 33(2), 136-43, 2007

Young, PP, Vaughan, DE, Hatzopoulos, AK. Biologic Properties of Endothelial Progenitor Cells and Their Potential for Cell Therapy. Prog Cardiovasc Dis, 49(6), 421-429, 2007 PMCID:1978244

Diez, H, Fischer, A, Winkler, A, Hu, CJ, Hatzopoulos, AK, Breier, G, Gessler, M. Hypoxia-mediated activation of Dll4-Notch-Hey2 signaling in endothelial progenitor cells and adoption of arterial cell fate. Exp Cell Res, 2006

Gialitakis, M, Kretsovali, A, Spilianakis, C, Kravariti, L, Mages, J, Hoffmann, R, Hatzopoulos, AK, Papamatheakis, J. Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A. Nucleic Acids Res, 34(3), 765-72, 2006 PMCID:1360741

Langer, H, May, AE, Daub, K, Heinzmann, U, Lang, P, Schumm, M, Vestweber, D, Massberg, S, Sch??nberger, T, Pfisterer, I, Hatzopoulos, AK, Gawaz, M. Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro. Circ Res, 98(2), e2-10, 2006

Montero-Balaguer, M, Lang, MR, Sachdev, SW, Knappmeyer, C, Stewart, RA, De La Guardia, A, Hatzopoulos, AK, Knapik, EW. The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish. Dev Dyn, 235(12), 3199-212, 2006

M??ller, II, Knapik, EW, Hatzopoulos, AK. Expression of the protein related to Dan and Cerberus gene--prdc--During eye, pharyngeal arch, somite, and swim bladder development in zebrafish. Dev Dyn, 235(10), 2881-8, 2006

Jakupoglu, C, Przemeck, GK, Schneider, M, Moreno, SG, Mayr, N, Hatzopoulos, AK, de Angelis, MH, Wurst, W, Bornkamm, GW, Brielmeier, M, Conrad, M. Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development. Mol Cell Biol, 25(5), 1980-8, 2005 PMCID:549365

Kupatt, C, Hinkel, R, Lamparter, M, von Br??hl, ML, Pohl, T, Horstkotte, J, Beck, H, M??ller, S, Delker, S, Gildehaus, FJ, B??ning, H, Hatzopoulos, AK, Boekstegers, P. Retroinfusion of embryonic endothelial progenitor cells attenuates ischemia-reperfusion injury in pigs: role of phosphatidylinositol 3-kinase/AKT kinase. Circulation, 112(9 Suppl), I117-22, 2005

Kupatt, C, Horstkotte, J, Vlastos, GA, Pfosser, A, Lebherz, C, Semisch, M, Thalgott, M, B??ttner, K, Browarzyk, C, Mages, J, Hoffmann, R, Deten, A, Lamparter, M, M??ller, F, Beck, H, B??ning, H, Boekstegers, P, Hatzopoulos, AK. Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia. FASEB J, 19(11), 1576-8, 2005

Conrad, M, Jakupoglu, C, Moreno, SG, Lippl, S, Banjac, A, Schneider, M, Beck, H, Hatzopoulos, AK, Just, U, Sinowatz, F, Schmahl, W, Chien, KR, Wurst, W, Bornkamm, GW, Brielmeier, M. Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol Cell Biol, 24(21), 9414-23, 2004 PMCID:522221

Wei, J, Blum, S, Unger, M, Jarmy, G, Lamparter, M, Geishauser, A, Vlastos, GA, Chan, G, Fischer, KD, Rattat, D, Debatin, KM, Hatzopoulos, AK, Beltinger, C. Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic lung metastases after intravenous delivery. Cancer Cell, 5(5), 477-88, 2004

Beck, H, Voswinckel, R, Wagner, S, Ziegelhoeffer, T, Heil, M, Helisch, A, Schaper, W, Acker, T, Hatzopoulos, AK, Plate, KH. Participation of bone marrow-derived cells in long-term repair processes after experimental stroke. J Cereb Blood Flow Metab, 23(6), 709-17, 2003

Vajkoczy, P, Blum, S, Lamparter, M, Mailhammer, R, Erber, R, Engelhardt, B, Vestweber, D, Hatzopoulos, AK. Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis. J Exp Med, 197(12), 1755-65, 2003 PMCID:2193947

Evans, V, Hatzopoulos, A, Aird, WC, Rayburn, HB, Rosenberg, RD, Kuivenhoven, JA. Targeting the Hprt locus in mice reveals differential regulation of Tie2 gene expression in the endothelium. Physiol Genomics, 2(2), 67-75, 2000

Hatzopoulos, AK, Folkman, J, Vasile, E, Eiselen, GK, Rosenberg, RD. Isolation and characterization of endothelial progenitor cells from mouse embryos. Development, 125(8), 1457-68, 1998

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