Personal History:Dr. Agnes Azimzadeh received her Ph.D. in Molecular and Cellular Biology and Immunology from the Institute of Molecular and Cellular Biology of the University Louis Pasteur in Strasbourg, France (1992). Her post-doctoral training at the Institute of Transplantation in Strasbourg included multiple collaborations with Pr. Jean-Paul Soulillou's team in Nantes (1993-99). She then joined the laboratory of Richard N Pierson as Research Assistant Professor at Vanderbilt University (1999-2002), before joining faculty as Assistant Professor in the Department of Surgery at University of Maryland Baltimore in 2002. She is a member of several professional societies. Dr Azimzadeh is a member of the Greenbaum Cancer Center Tumor Immunology and Immunotherapy group since 2009.
Research Interests:The overall goal of Dr. Azimzadehâ?Ts research is to understand and prevent the mechanisms of rejection of transplanted organs. Organ transplantation is the preferred method of treatment for many forms of end-stage organ failure. However, immunosuppressive drugs used to avoid rejection result in numerous undesirable effects (infection, malignancy, hypertension, diabetes, accelerated arteriosclerosis). Moreover, they are not effective at preventing chronic rejection resulting in late graft loss.
Using various transplant models, we evaluate selective new immunomodulatory therapies for their ability to moderate innate and adaptive immunity and to promote immune tolerance, while sparing responses to vaccines and tumors.
We are particularly interested in the role played by costimulation signals and their effects on the host immune response, including inhibition of memory T cell and humoral responses and stimulation of regulatory T cells development and function. We are using a single chain antibody fragment to selectively block the T cell receptor CD28 and antibodies or fusion proteins to block other pathways.
The development of autoimmunity after organ transplantation has been recently recognized in murine transplant models and humans. We described similar results in non-human primates and are currently characterizing these responses with the hope to intervene with these immune responses to prevent cardiac chronic rejection.
Through collaborations with several investigators and industry, we are evaluating the role of Fc receptors and other therapies in transplant biology.
Another aspect of our research involves the study of transplantation across species: Xenografts. We are interested by the role of pro-inflammatory mediators such as complement and TLR agonists and proteoglycans in activating platelets and neutrophils in the rejection of xenografts. The laboratory uses genetically-engineered mouse and pig models and is applying cellular immunological, biochemical, and molecular approaches to mouse and non-human primate transplantation models.
Lab Techniques and Equipment:• Murine and non-human primate transplant models
• Transgenic mouse models of transplantation
• Cellular immunology assays (CSFE-MLR, ELISPOT)
• Adoptive cell transfer
• Flow cytometry
• Real-time PCR
• Histology, ELISA, western-blot
Azimzadeh A & Van Regenmortel MHV. (1990). Antibody affinity measurements. J. Mol. Recognition, 3: 108-116.
Azimzadeh A & Van Regenmortel MHV. (1991). Measurement of affinity of viral monoclonal antibodies by ELISA titration of free antibody in equilibrium mixtures. J. Immunol. Methods, 141: 199-208.
Azimzadeh A, Weiss E & Van Regenmortel MHV. (1992). Measurement of affinity of viral antibodies using Fab'-peroxidase conjugate. Influence of antibody concentration on apparent affinity. Mol. Immunol., 29: 601-608.
Azimzadeh A, Pellequer JL & Van Regenmortel MHV. (1992). Operational aspects of antibody affinity constants measured by liquid-phase and solid-phase assays. J. Mol. Recognition, 5: 9-18.
Azimzadeh A, Wolf P, Dalmasso A P, Odeh M, Beller JP, Fabre M, Charreau B, Thibaudeau K, Soulillou JP & Anegon I. (1996). Assessment of hyperacute rejection in a rat-to-primate cardiac xenograft model. Transplantation, 61: 1305-1313.
Azimzadeh A, Meyer C, Ravanat C, Cazenave JP, & Wolf P. (1996). Xenograft rejection : molecular mechanisms and therapeutic prospects. Hematol. and Cell Therapy, 38: 331-343.
Azimzadeh A, Wolf P, Thibaudeau K, Cinqualbre J, Soulillou JP & Anegon I. (1997). Comparative study of target antigens for primate xenoreactive natural antibodies in pig and rat endothelial cells. Transplantation, 64: 1166-1174
Azimzadeh A, Meyer C, Watier H, Beller JP, Chenard-Neu MP, Kieny R, Boudjema K, Jaeck D, Cinqualbre J, & Wolf P. (1998). Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.
Transplant Immunology, 6: 13-22
Azimzadeh A, Romain N, Vermot-Desroches C, Ravanat C, Chenard MP, Widjenes J, Herve P, Jaeck D & Wolf P. (1998). Antibodies to human adhesion molecules and von Willebrand factor: In vitro cross-species reactivity in the xenotransplantation setting. Xenotransplantation, 5: 284-291.
David P, Viollon C, Alexandre E, Azimzadeh A, Nicod L, Wolf P, Jaeck D, Boudjema K & Richert L. (1998). Metabolic capacities in cultured human hepatocytes obtained by a new isolating procedure from non-wedge small liver biopsies.
Hum. Exp. Toxicol., 17: 544-553.
Meyer C, Wolf P, Romain N, Ravanat C, Roussi J, Beller JP, Imbs P, Chenard MP, Fabre M, Kieny R, Bonneau M, Drouet L, Cazenave JP, Soulillou JP & Azimzadeh A. (1999). Use of von Willebrand diseased kidney as donor in a pig-to-primate model of xenotransplantation. Transplantation, 67: 38-45.
Charreau B, Menoret S, Tesson L, Azimzadeh A, Audet M, Wolf P, Marquet R, Verbakel C, Ijzermans J, Cowan P, Pearse M, D'apice A, Soulillou JP, Anegon I. (1999). Protection against hyperacute xenograft rejection of transgenic rat hearts expressing human decay accelerating factor (hDAF) transplanted into primates. Molecular Medicine, 5: 617-630.
Van Regenmortel MH, Azimzadeh A. (2000). Determination of antibody affinity. J Immunoassay, 21: 211-234.
David P, Alexandre E, Chenard-Neu MP, Audet M, Wolf P, Jaeck D, Azimzadeh A, Richert L. (2001). Engraftment and functionality of fresly isolated and cryopreserved Sprague-Dawley rat hepatocytes after intrasplenic transplantation in analbuminemic rats. Cell transplantation, 10: 67-80.
Kaulek V, Saas P, Alexandre E, Grant H, Richert L, Jaeck D, Tiberghien P, Wolf P, Azimzadeh A (2001). Comparative phenotype and immunogenicity of freshly isolated and immortalized rat hepatocytes. Cell transplantation, 10:739-47.
Pierson RN III, Macchiarini P, Azimzadeh A (2001). Understanding hyperacute rejection of the lung: is this a special case? Graft, 4:10-13.
Pierson RN III, Crowe JE, Pfeiffer S, Atkinson J, Azimzadeh A, Miller G. (2001) CD40-ligand in primate cardiac allograft and viral immunity. Immunologic Research, 3: 253-262.
Pfeiffer S, Zorn GL III, Kelishadi S, Oriol R, Wolf P, Pierson RN III, Azimzadeh A (2001). Role of anti-Galï¡1,3Gal and anti-platelet antibodies in hyperacute rejection of pig lung by human blood. Ann Thorac Surg, 72:1681-9; discussion 1690
Kessler L, Azimzadeh A, Wiesel ML Coumaros G, Chakfe N, Soyer C, Koehl C, Cazenave JP, Wolf P, Pinget M. (2001). Effect of insulin on von Willebrand factor release in normal and diabetic subjects: in vivo and in vitro studies. Horm Metab Res., 33:674-80
Pierson RN III, Loyd JE, Goodwin A, Majors D, Dummer JS, Mohacsi P, Wheeler A, Bovin N, Miller GG, Olson S, Johnson J, Rieben R, Azimzadeh A. (2002). Successful management of an ABO mismatched lung allograft using antigen-specific immunoadsorption, complement inhibition, and immunomodulatory therapy. Transplantation, 74:79-84.
Azimzadeh A, Zorn GL III, Blair KSA, Zhang JP, Pfeiffer S, Harrison RA, Cozzi E, White DJG, Pierson RN III. (2002). Hyperacute lung rejection in the pig-to-human model. 2) Synergistic effect of soluble and membrane complement inhibition to attenuate porcine pulmonary hyperacute rejection. Xenotransplantation, 10: 120-131.
Schroeder C, Pfeiffer S, Wu G, Zorn G II, Ding L, Allen C, Harrison R, White D, Azimzadeh A, Pierson RN III. (2003). Effect of C1 esterase inhibition on survival of h-DAF pig lungs perfused with human blood.
J. Heart Lung Transplant., 22:1365-75.
Pfeiffer S, Zorn G III, Zhang JP, Giorgio T, Robson S, Azimzadeh A, Pierson RN III. (2003). Hyperacute lung rejection in the pig-to-human model. 3) Platelet receptor inhibitors synergistically modulate complement activation and lung injury. Transplantation, 75: 953-9.
Crowe J, Sannella E, Pfeiffer S, Zorn Z III, Azimzadeh A, Newman R, Miller G, Pierson RN III. (2003). CD154 regulates primate immunity to influenza. Am. J. Transplant., 3:680-8.
Schroder C, Azimzadeh AM, Wu G, Price JO, Atkinson JB, Pierson RN III. (2003) Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys. Transplant Immunology, 12: 19-28.
Schroder C, Wu GS, Price E, Johnson JE, Pierson RN 3rd, Azimzadeh A. (2003). Hyperacute rejection of mouse lung by human blood: characterization of the model and the role of complement. Transplantation, 76:755-60.
Motsinger A, Azimzadeh A, Stanic AK, Johnson RP, Van Kaer L, Joyce S, Unutmaz D. (2003). Identification and simian immunodeficiency virus infection of CD1d-restricted macaque natural killer T cells. J Virol., 77:8153-8.
Poston RS, Gu J, Prastein D, Gage F, Hoffman JW, Kwon M, Azimzadeh A, Pierson RN 3rd, Griffith BP. (2004). Optimizing donor heart outcome after prolonged storage with endothelial function analysis and continuous perfusion. Ann Thorac Surg., 78:1362-70.
Pfeiffer S, Zorn G III, Blair K, Farley S, Wu G, Schuurmann HK, Azimzadeh A, Pierson RN III. (2005). Hyperacute lung rejection in the pig-to-human model. 4) Evidence for complement- and antibody independent mechanisms. Transplantation, 79:662-71.
Nguyen B, Zwets E, Schroeder C, Pierson RNIII, Azimzadeh A. (2005) Beyond antibody-mediated rejection: hyperacute xenotranplant lung rejection as a paradigm for dysregulated inflammation. Current Drug Targets: Cardiovascular and Haematological Disorders, 5 : 255-69.
Azimzadeh A, Pfeiffer S, Wu G, Schroeder C, Zorn G III, Kehry M, Miller G, Rose M, Pierson RNIII. (2005) Humoral immunity to vimentin is associated with cardiac allograft injury in nonhuman primates, and is partially regulated by CD154. Am. J. Transplantation, 5 : 2349-2359.
Azimzadeh A, Pfeiffer S, Wu G, Schroeder C, Zorn G III, Kelishadi S, Ozkaynak E, Kehry M, Atkinson J, Miller G, Pierson RNIII (2006). Alloimmunity in primate heart recipients with CD154 blockade: evidence for alternative costimulation mechanisms. Transplantation, 81 : 255-264.
Schroder C, Pfeiffer S, Wu G, Azimzadeh A, Aber A, Pierson RN 3rd,O'Sullivan MG (2006). Simian parvovirus infection in cynomolgus monkey heart transplant recipients causes death related to severe anemia. Transplantation, 27;81:1165-70.
Ndejembi MP, Teijaro JR, Patke DS, Bingaman AW, Chandok MR, Azimzadeh A, Nadler SG, Farber DL (2006). Control of memory CD4 T cell recall by the CD28/B7 costimulatory pathway. J Immunol. 177 :7698-706.
Wu G, Pfeiffer S, Schroder C, Zhang T, Nguyen BN, Kelishadi S, Atkinson JB, Schuurman HJ, White DJ, Azimzadeh A, Pierson RN 3rd (2007). Coagulation cascade activation triggers early failure of pig hearts expressing human complement regulatory genes. Xenotransplantation, 14 :34-47.
Barrows BR, Azimzadeh A, McCulle SL, Vives-Rodriguez G, Stark WN Jr,Ambulos N, Yin J, Chen H, Balke CW, Moravec CS, Pierson RN 3rd, Gottlieb SS, Bond M, Johnson FL. (2007) Robust gene expression with amplified RNA from biopsy-sized human heart tissue. J Mol Cell Cardiol., 42:260-4.
Nguyen BN, Azimzadeh AM, Zhang T, Wu G, Shuurman HJ, Sachs DH, Ayares D, Allan JS, Pierson RN. (2007) Life-supporting function of genetically modified swine lungs in baboons. J. Thorac. Cardiovasc. Surg., 133:1354-63.
Schroder C, Pierson RN III, Nguyen BN, Kawka DW, Peterson LB, Wu G, Zhang T, Springer MS, Siciliano SJ, Iliff S, Ayala JM, Lu M, Mudgett JS, Lyons K, Mills SG, Miller GG, Singer II, Azimzadeh AA, DeMartino JA. (2007) CCR5 blockade modulates inflammation and alloimmunity in primates. J. Immunol. 179:2289-99.
Chess DJ, Lei B, Hoit BD, Azimzadeh AM, Stanley WC. (2007) Deleterious effects of sugar and protective effects of starch on cardiac remodeling, contractile dysfunction, and mortality in response to pressure overload.
Am J Physiol Heart Circ Physiol. 293:1853-60.
Silverman RP, Banks ND, Detolla LJ, Shipley ST, Panda A, Sanchez RA, Azimzadeh AM, Pierson RN 3rd, Wang D, Rodriguez ED, Holton LH 3rd, Bartlett ST. (2008) A heterotopic primate model for facial composite tissue transplantation. Ann Plast Surg. 60:209-16.
Tang AL, Teijaro JR, Njau MN, Chandran SS, Azimzadeh A, Nadler SG, Rothstein DM, Farber DL. (2008) CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis. J Immunol. 181:1806-13. PubMed PMID: 18641318; PubMed Central PMCID: PMC2683757.
Ezzelarab M, Garcia B, Azimzadeh A, Sun H, Lin CC, Hara H, Kelishadi S, Zhang T, Lin YJ, Tai HC, Wagner R, Thacker J, Murase N, McCurry K, Barth RN, Ayares D, Pierson RN 3rd, Cooper DK. (2009) The innate immune response and activation of coagulation in alpha1,3-galactosyltransferase gene-knockout xenograft recipients. Transplantation. 87:805-12. PubMed PMID: 19300181.
Kelishadi S.*, Azimzadeh A.*, Zhang T.*, Stoddard T., Welty E., Avon C., Higuchi M., Laaris A., Cheng X, McMahon C., Pierson R. III (2010) Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys. J. Clin. Investigation, 120: 1275-84. PMID: 20335656.
Poirier N.*, Azimzadeh A.*, Zhang T.*, Dilek N., Mary C., Nguyen B., Tillou X., Wu G., Reneaudin K., Hervouet J., Martinet B., Coulon F, Allain-Launay E., Karam G., Soulillou J-P, Pierson R.N. III#, Blancho G#, Vanhove B# (2010) Inducing CTLA-4-dependent immune regulation by selective CD28 blockade promotes regulatory T cells in organ transplantation. Science Transl. Med. 2:17ra10. PMID: 20371478.
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