AG Gattermann

The focus of the Gattermann/Majidi group is on

• decifering the pathophysiology of the ring sideroblastic phenotype (mitochondrial iron overload of erythroblasts) in patients with myelodysplastic syndromes (MDS)
• investigating hematopoetic stem cell differentiation, particularly under the influence of inhibition of the NEDDylation pathway with Pevonedistat
• searching for new prognostic biomarkers in MDS using multicolour immun­histo­chemistry on a tissue microarray

Detection of FECH-ABCB7 interaction in F36P cells using proximity ligation assay (PLA)

In 2020, the group started establishing a modern fluorescence microscopy unit (Mantra system by Perkin-Elmer; invert fluorescence microscope from Keyence). The facility includes advanced software modules for 3D imaging. Clear optical sectioning is achieved through an electronic projection element that eliminates scattered light in the Z direction. Precise image stitching is also possible.

• These technical features enable high-quality analyses using the established MDS/AML tissue microarray. The recently acquired Sectioning Module will also enable analysis of 3D bone marrow cultures.
• OPAL technology for multicolour immunohistochemistry has been implemented and allows for up to 7 different fluorochromes to be specifically attached to target structures on the same tissue section. Expression patterns are subsequently analysed using Inform Software.

The Gattermann/Majidi group is happy to share the above-mentioned technology with other working groups.

Current projects:

• siRNA knockdown of Ferrochelatase, ABCB7, and GLRX5  in hematopoietic stem cells for induction of a sideroblastic phenotype in erythroblasts. Implementation of 3D bone marrow cultures using Alvetex membranes.
• Influence of Pevonedistat (first-in-class Neddylation inhibitor) on normal hematopoietic stem cell subsets and immune cell composition (cell cultures, flow cytometry, proximity ligation assay).
• Effect of Tenascin-C (component of extracellular matrix) on hematopoietic stem cells.
• Prognostic significance of the expression of fibrosis markers (e.g. Gli1) in the MDS bone marrow (multicolour fluorescence immunostaining (OPAL assay), tissue microarray).

Multispectral composite image of MDS bone marrow