CURRENT CLINICAL INTERESTS
Translational cell therapy, specifically cellular immunotherapy. 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.
Clinical/applied: His Cell Therapy Group 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 and routine clinical cell therapy products predominantly for immunotherapy and regenerative medicine. Besides technology development, T-cell based therapeutics, both primary and engineered, have been a major focus. The Department maintains partnerships with academic and commercial entities invested in cellular therapy. He is also interested in cell donor safety and ethics.
Basic research: The Hematopoietic Stem Cell Research Group is investigating stem cell-niche interactions, specifically in the context of stem cell mobilization/stem cell maintenance and disruption of leukemia stem cell-niche interactions with a view to leukemia cell eradication. Aberrant CXCR4 signaling in the context of normal and malignant hematopoiesis remains a research focus. Recent advances include pre-clinical and clinical development of a novel, highly potent CXCR4 antagonist (POL6326) and the discovery of an endogenous CXCR4 antagonist (EPI-X4) which is cleaved, in an acidic milieu, off of albumin and according to preliminary data contributes to the integrity of the mucosal barrier.
Hsieh YT et al. (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.
Karpova D et al. (2013) The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor. Leukemia 27:2322-2331
Kolodziej S et al. (2014) Influence of PADI4 on histone arginine methylation differentially regulates expression of the Tal1 target genes IL6ST and CTCF. Nature Communications 5:3995
Belz K et al. (2014) Smac mimetic and glucocorticoids synergize to induce apoptosis in childhood ALL my promoting ripoptosome assembly. Blood 124:240-50
Schönfeld K et al. (2015) Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an ErbB2/HER2-Specific Antigen Receptor. Mol Ther 23:330-8
Kraft D et al. (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
Zirafi O et al. (2015) Discovery and characterization of an endogenous CXCR4 antagonist. Cell Reports 11:737-47
Kuvardina ON et al. (2015) RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation. Blood 125:3570-9