Immune Pharmacology -
Prof. Dr. Heinfried H. Radeke

Expertise

Role of sphingosin-1-phosphate receptors and sphingolipid enzymes for the function of lymphocytes and dendritic cells.
Isolation, differentiation and characterization of diverse types of dendritic cells from different murine and human tissues
Extended expertise for current und upcoming immunosuppressants, such as glucocorticoids, SEGRAs, vitamin D, ciclosporin, FK506, chemokine antagonists or FTY720
“in vivo” mouse models of chronic inflammation, like the inflammatory bowel disease, with oncogenic potential and the tendency to develop colon cancer; additionally “in vitro” models of chronic inflammation and autoimmune diseases with respective primary cell isolates and cellular migration systems
Static and dynamic test systems including the development of respective computer assisted analysis systems to measure adhesion, chemotaxis and transmigration of immune cells in vitro and in vivo
Screening and evaluation of novel gene, protein and cellular delivery systems, e.g. lentiviral expression vectors optimized for immune cells that deliver cDNA expression, dominant negative mutants, shRNAs or TFOs („triple helix forming oligo nucleotides“), and in combination with immunoliposomes allow endothelial cell detection and targeting.
Detailed assessment and monitoring of immunological parameters in human patients, especially in Nephritis, Kidney Transplantation, Rheumatoid Arthritis, Inflammatory Bowel Disease, Autoimmune Endocrinopathy and during the phase of immune reconstitution following BM- or stem cell transplantation; with special expertise towards biologics and other biological pharmaceutics.
Profound experimental and background knowledge about generation and signaling of reactive oxygen species (ROS)

Resources and Abilities

96 well „high throughput“ single cell analysis microscope-video-computer system (Zeiss/ Hamamatsu/ Improvision) for automated chemotaxis assay analysis and fluorochrome-based signal transduction studies
Endothelial flow chamber – video microscopic systems including an optimized, computerized video analysis software “Imagoquant™”
Lentiviral transduction systems especially for transduction and expression of cDNAs, TFOs and shRNAs in dendritic cells
Eukaryotic and Prokaryotic cloning and protein expression system
High-volume Sartorius Cross-Flow Protein Purification System (DFG loan)
Automated ELISA Spot Assay Video Analysis System: single and dual color ELISPOT including the possibility to develop new assays to measure frequencies of protein or cytokine secreting cells
BiaCor X100 system for binding and protein interaction studies

Staff

Dr. Carolin Daniel (Colitis models, Vitamin D, FTY720, z.Z. in Boston)
Cornelia Richter (Dendritic cell isolation and differentiation, ELISPOT)
Matthias Schröder (Cell fractionation, sphingolipid metabolism)
Oliver Giegold (Endothelial flow chamber, computer analyses)

Publications

Giegold O, Ludwig RJ, Hardt K, Will J, Schön MP, Oostingh GJ, Pfeilschifter JM, Boehncke WH, Radeke HH: Computer-aided analysis of cell-interactions under dynamic flow conditions. Experimental Dermatology 2008, in press.
Daniel C, Sartory NA, Zahn N, Radeke HH*, Stein J*: Immune modulatory treatment of TNBS colitis with calcitriol is associated with a change of a Th1/Th17 to a Th2 and regulatory T cell profile. [*contributed equally]. J Pharmacol Exp Ther 2008, 324:23-33.
Daniel C, Sartory N, Zahn N, Schmidt R, Geisslinger G, Radeke HH*, Stein J*: FTY720 directly affects T helper type 2 effector functions via the IL-1 receptor-related protein T1/ST2 to ameliorate oxazolone-colitis in mice. [*contributed equally]. Mol Immunol 2007, 44:3305-3316.
Behrens F, Himsel A, Rehart S, Stanczyk J, Beutel B, Zimmermann SY, Köhl U, Moeller B, Gay S, Kaltwasser JP, Pfeilschifter JM, Radeke HH: Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthritis. Ann Rheum Dis 2007, 66:1151-1156.
Daniel C, Sartory N, Zahn N, Geisslinger G, Radeke HH*, Stein J*: FTY720 ameliorates Th1-mediated colitis in mice by directly affecting the functional activity of CD4+CD25+ regulatory T cells. [*contributed equally]. J Immunol 2007, 178:2458-2468.
Waibler Z, Kalinke U, Will J, Herrero San Juan M, Pfeilschifter JM, Radeke HH: TLR-ligand stimulated interleukin-23 subunit expression and assembly is regulated differentially in murine plasmacytoid and myeloid dendritic cells. Mol Immunol 2007, 44:1483-1489.
Rubant S, Schwarz M, Werner E, Luttmann R, Ludwig RJ, Boehncke WH, Pfeilschifter JM, Radeke HH: Eukaryotic expression of the broad-spectrum chemokine receptor antagonist vMIP-II and its effects on T-cell function in vitro and in vivo. Exp Dermatol 2006, 15:634-642.
Hauser IA, Spiegler S, Kiss E, Gauer S, Sichler O, Scheuermann EH, Ackermann H, Pfeilschifter JM, Geiger H, Gröne H-J, Radeke HH: Prediction of acute renal allograft rejection by urinary monokine induced by IFN-? (MIG). J Am Soc Nephrol 2005, 16:1849-1858.
Radeke HH, von Wenckstern H, Stoidtner K, Schraut C, Kleuser B: Overlapping signaling pathways of sphingosine 1-phosphate and transforming growth factor-β in murine Langerhans cells. J Immunol 2005, 174:2778-2786.
Kautz K, Schwarz M, Radeke HH: Interference with MCP-1 gene expression by vector generated triple helix-forming RNA oligonucleotides. Cell Mol Life Sci 2005, 62:362-376.
Radeke HH, Janssen-Graalfs I, Sowa EN, Chouchakova N, Skokowa J, Löscher F, Schmidt RE, Heeringa P, Gessner JE: Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis. J Biol Chem 2002, 277:27535-27544.
Radeke HH, Tschernig T, Karulin A, Schumm G, Emancipator SN, Resch K, Tary-Lehmann M: CD4+ T cells recognizing specific antigen deposited in glomeruli cause glomerulonephritis-like kidney injury. Clin Immunol 2002, 104:161-173.