Stem Cell Lab 2 (MK1-L11)
Background
Located within specific anatomical zones of the skeleton, the bone marrow (BM) is a specialized microenvironment or “niche” that lodges cells of hematopoietic and mesenchymal origins in various hierarchical committed states. The main role of the BM niche is the tight control of cell-fate decisions of the hematopoietic stem cells (HSCs) and their progeny to sustain the daily supply in functional blood and immune cells throughout life. These environmental cues are produced by a variety of stromal cells that constitute the BM niche which mainly include neurons, endothelial cells and mesenchymal stromal cells (MSCs). The latter are considered a versatile stem cell population due to their capacity to differentiate into bone (osteoblasts), cartilage (chondrocytes) and fat cells (adipocytes), thus playing a central role in HSCs maintenance, BM niche composition and life-long turnover and bone growth.
In health, the bone marrow niche maintains a harmonious interplay between different cellular entities, including HSCs, MSCs, endothelial cells, immune cells, and osteoblasts, as well as an intricate network of signaling molecules. This spatial organization is not static but dynamically influenced by temporal factors, such as circadian rhythms, aging, and responses to physiological stresses. The collective effect of this spatial-temporal crosstalk determines the fate decisions of HSCs, balancing their self-renewal, quiescence, and differentiation to sustain a functional hematopoietic system.
The balanced BM homeostasis can be disrupted, giving rise to a spectrum of hematologic pathologies. Dysregulation of the spatial-temporal crosstalk has been implicated in BM failure syndromes, hematopoietic malignancies, and other disorders affecting blood cell production but also different treatment strategies such as chemotherapy and stem cell transplantation.
Research
The group of Manja Wobus has long-term translational research experience in the field of Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). The major research focus of our group is on the characterization of the interaction of HSCs and leukemic clones within the bone marrow microenvironment and the consecutive bidirectional sequelae. Along these lines, highly innovative 2D and 3D co-culture models have been developed to delineate the impact of the stromal environment on the leukemogenesis and disease persistence, interrogating the role of MSC-derived extracellular matrix (ECM) and vesicles (EVs) as well as cell-cell interactions in patients with MDS and AML.
PhD projects
- Metabolic reprogramming of the hematopoetic microenvironment in acute myeloid leukemia (Anastasia Sidorenkova)
- 3D bone marrow niche mimics for drug screening and the development of new therapeutic strategies for AML (Hannah Botterer)
Further projects
- The role of extracellular matrix ECM for malignant transformation
- Monocyte-MSC crosstalk in the myelodysplastic BM microenvironemt
- Impact of stromal-leukemic cell interactions for therapy response
Members
- Prof. Dr. rer. nat. Manja Wobus, group leader
- Anna-Lena Baumann, M.Sc., research associate
- Dipl. Biochem. Kristin Möbus, technician, academic coordination
- Katrin Müller, technician
- Robert Kuhnert, technician
- Anastasia Sidorenkova, PhD student
- Hannah Botterer, PhD student