CURRENT CLINICAL INTERESTS
Translational development (manufacturing, quality control, regulatory affairs) of cellular therapies for cell-based immuno-, regenerative or gene replacement therapies, generation of clinical cellular therapeutics, stem cell mobilization
CURRENT RESEARCH INTERESTS
Interactions of normal or malignant stem cells with the bone marrow niche, stem cell mobilization, stem cell expansion
Dr. Bönig is pursuing two largely independent research programs, one applied and one basic.
His GMP laboratory is developing GMP- and EP-compatible, fully regulator-approved processes for manufacturing and testing of cell-based therapeutics, including Advanced Therapy Medicinal Products (ATMPs). The GMP-facility, after formal process and assay validation and regulatory approval, generates clinical trial specimen as well as routine clinical products for a broad range of indications pertaining to cellular immunotherapy, cellular regenerative therapy and cell-based gene (and gene replacement) therapy, for European-wide use. For the last several years, besides technology development, T-cell based therapeutics, both primary and engineered, have been a major focus. In addition to academic collaborations, the Department maintains R&D as well as CMO type partnerships with several commercial entities invested in cellular therapy.
The Hematopoietic Stem Cell Research Group is focused on the investigation of stem cell-niche interactions, specifically in the context of stem cell mobilization and disruption of leukemia stem cell-niche interactions with a view to leukemia cell eradication. Recent advances include a novel CXCR4 antagonist with a mobilization efficacy significantly in excess of currently available compounds (currently in clinical trials) and the identification of VLA4 interference as a modality for acute lymphoblastic leukemia eradication.
Dr. Bönig maintains close ties with the University of Washington, specifically through collaborations with the Papayannopoulou and Kiem laboratories, and regularly travels between Frankfurt and Seattle.
Schulz M and Bonig H (2016) Update on biosimilars of G-CSF - when no news is good news. Current Opinion in hematology 2016 Jan;23(1):61-6.
Chow K, Luxembourg B, Seifried E, Bonig H(2016) Spleen size is significantly influenced by body height and gender: Establishment of normal values for spleen size by ultrasound based on a cohort of 1200 normal healthy individuals. Radiology Oct 26: 150887 (e-pub ahead of print).
Featured in Dtsch Arztebl 2016;113(4): A-143.
Karpova D, Bonig H (2015) CXCR4/CXCL12 signaling in immature hematopoiesis - lessons from pharmacological and genetic models. Stem Cells 33:2391-9.
Kuvardina ON, Herglotz J, Kolodziej S, Kohrs N, Herkt S, Wojcik B, Oellerich T, Serve H, Bonig H, Stocking C, Rieger MA, Lausen J (2015) RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation. Blood 125:3570-9.
Zirafi O, Kim KA, Staendker L, Mohr KB, Sauter D, Heigele A, Kluge SF, Wiercinska E, Chudziak D, Richter R, Moepps B, Gierschik P, Vas V, Geiger R, Lamla M, Weil T, Burster T, Zgraja A, Daubeuf F, Frossard N, Hachet-Haas M, Heunisch F, Reichetzeder C, Galzi JL, Castells JP, Canales-Mayordomo A, Jimenez-Barbero J, Gimenez-Gallego G, Schneider M, Shorter J, Telenti A, Hocher B, Forssmann WG, Bonig H, Kirchoff F, Muench J (2015) Discovery and characterization of an endogenous CXCR4 antagonist. Cell Reports 11:737-47
Kraft D, Rall M, Volcic M, Metzler E, Groo A, Stahl A, Bauer L, Nasonova E, Salles D, Taucher-Scholz G, Bonig H, Fournier C, Wiesmuller L (2015) NF-kB-dependent DNA damage-signaling differentially regulates DNA double-strand break repair mechanisms in immature and mature human hematopoietic cells. Leukemia 29:1543-54.
Schonfeld K, Sahm C, Zhang C, Naundorf S, Brendel C, Odendahl M, Nowakowska P, Bonig H, Kohl U, Kloess S, Kohler S, Holtgreve-Grez H, Jauch A, Schmidt M, Kuhlcke K, Seifried E, Klingemann HG, Rieger MA, Tonn T, Grez M, Wels WS (2015) Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an ErbB2/HER2-Specific Antigen Receptor. Mol Ther 23:330-8.
Hsieh QT, Jiang E, Shisido S, Kim HN, Pham J, Esguerra ZA, Kwok E, Jang J, Bonig H, Biediger RJ, Vanderslice P, Kim QM (2014) Effects of the small-molecule inhibitor of VLA4, TBC3486, on pre-B-ALL cells. Leukemia 28:2101-4.
Belz K, Schoeneberger H, Wehner S, Bonig H, Klingebiel T, Fulda S (2014) Smac mimetic and glucocorticoids synergize to induce apoptosis in childhood ALL by promoting ripoptosome assembly. Blood 124:240-50.
Kolodziej S, Kuvardina ON, Herglotz J, Backert I, Bonig H, Karas M, Proschak E, Lausen J (2014) Influence of PADI4 on histone arginine methylation differentially regulates expression of the Tal1 target genes IL6ST and CTCF. Nature Communications 5:3995.
Karpova D, Dauber K, Spohn G, Chudziak D, Wiercinska E, Schulz Me, Pettit AR, Levesque JP, Romagnoli B, Patel K, Chevalier E, Dembowsky K,Bonig H (2013) The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor. Leukemia 27:2322-2331.
Bonig H and Papayannopoulou T (2013) Stem Cell Mobilization: Updated conceptual renditions Leukemia 27:24-31
Hsieh YT*, Gang EJ*, Geng H, Park E, Huantes S, Chudziak D, Dauber K, Schaefer P, Scharman C, Shimada H, Syemedi S, Klemm L, Loh M, Kang ES, Koo HH, Hofmann WK, Andrade J, Crooks GM, Willman CL, Muschen M, Papayannopoulou T, Heisterkamp N, Bonig H*, Kim YM* (2013) VLA4 blockade eradicates drug resistant pre-B acute lymphoblastic leukemia. Blood 121:1814-8 (*equal contribution)
Featured in Newswatch, Cancer Discovery January 24, 2013, DOI: 10.1158/2159-8290. CD-RW2013-019