Description of Research Expertise:
Production and characterization of pathogenic human monoclonal auto- and alloantibodies
My laboratory is interested in characterizing the human immune response to auto- and alloantigens on a molecular level in order to understand more about human immune repertoire development. Our goal is to use this information to develop specific therapeutic agents that down-regulate immune responses in the settings of autoimmune disease such as immune hemolytic anemias and thrombocytopenias, transfusion reactions, hemolytic disease of the newborn, and acute rejection of solid organ allografts.
To approach these problems experimentally, we have combined Fab/phage-display technology with a novel cell-surface panning method to isolate large arrays of clinically significant human monoclonal antibodies from individual patients. This approach has enabled us to study the genetic and immunological properties of pathogenic auto- and alloantibodies.
Chen, J., Zheng, Q., Hammers, C.M., Ellebrecht, C., Mukherjee, C., Tang, H-Y., Lin, C., Yuan, H-J., Pan, M., Langenhan, J., Komorowski, L., Siegel, D.L., Payne, A.S., Stanley, J.R.: Proteomic analysis of pemphigus autoantibodies indicates a much larger, more diverse, and dynamic repertoire than determined by B-cell genetics Cell Reports 18 : 237-247,2017.
Villa C.H., Cines D.B., Siegel D.L., Muzykantov V.R.: Erythrocytes as carriers for drug delivery in blood transfusion and beyond Transfusion Medicine Reviews 31 : 26-35,2017.
Carnemolla, R., Villa, C.H., Greineder, C.F., Zaitsev, S., Kowalska, A., Atochin, D.N., Cines, D.B., Siegel, D.L., Esmon, C.T. Muzykantov, V.R.: Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia-reperfusion injury FASEB J 31 : 761-770,2017.
Beigel, J.H., Tebas, P., Elie-Turenne, Marie-Carmelle, et al: Immune plasma for the treatment of severe influenza: an open-label, multicenter, phase 2 randomised study The Lancet Respiratory Medicine 5 : 500-511,2017.
Ostertag, E.M., Bdeir, K., Kacir, S., Thiboutot, M., Gulendran, G., Yunk, L., Hayes, V.M., Motto, D.G., Poncz, M., Zheng, X.L., Cines, D.B., Siegel, D.L.: ADAMTS13 Autoantibodies Cloned from Patients with Acquired Thrombotic Thrombocytopenic Purpura: 2. Pathogenicity in an animal model Transfusion 56 : 1775-1785,2016.
Villa C.H., Pan D.C., Johnston I., Greineder C.F., Cines D.B., Poncz M., Siegel D.L., Muzykantov V.: Coupling therapeutics to human erythrocytes demonstrates target-dependent effects on red cell physiology while preserving efficacy Blood 128 : 701,2016.
Bhoj V., Nunez-Cruz S., Feldman M.D., Mansfield K., Rader C., Siegel D.L., Milone M.C.: Immunotherapy of medullary thyroid carcinoma by GDNF family receptor alpha 4 (GFR4)-targeted adoptive T cell immunotherapy American Association for Cancer Research 2016 Annual Meeting, New Orleans, LA. : 2016.
Siegel D.L., Westhoff, C: Rh and LW Blood Groups Rossi’s Principles of Transfusion Medicine : 2016.
Zhao A., Tohidkia M.R., Siegel D.L., Coukos G., Omidi Y.: Phage antibody display libraries: a powerful antibody discovery platform for immunotherapy Critical Reviews in Biotechnology 36 : 276-289,2016.
Ostertag, E.M., Kacir, S., Thiboutot, M., Gulendran, G., Zheng, X.L., Cines, D.B., Siegel, D.L.: ADAMTS13 Autoantibodies Cloned from Patients with Acquired Thrombotic Thrombocytopenic Purpura: 1. Structural and functional characterization in vitro Transfusion 56 : 1763-1774,2016.
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