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Master thesis / Semester project: The role of DAMPs in low back pain
This project investigates how hematopoiesis is affected by damage-associated molecular patterns (DAMPs). Methods: isolation, culture, and differentiation of bone marrow stromal cells (MSC) and hematopoietic stem and progenitor cells (HSPC), qPCR, ELISA
Low back pain is the world’s most disabling condition and often coincides with painful vertebral bone marrow lesions (“Modic changes”). We have recently shown that the bone marrow of Modic changes is fibrotic and that the maturation of myeloid cells is dysregulated. Cartilage breakdown products are extracellular matrix-derived DAMPs draining from the adjacent degenerated intervertebral disc into the bone marrow. They appear to be key in the pathogenesis of Modic changes. In this project we investigate the global mechanism how DAMPs modulate hematopoietic and mesenchymal stem cell lineage choice, how this causes fibrosis and dysmyelopoiesis, and we test novel therapeutics to inhibit this key process.
Fresh human vertebral bone marrow aspirates will be used for this project. The project will be conducted at the new Balgrist Campus, a musculoskeletal research institution with research groups from UZH, ETH, and industry.
Low back pain is the world’s most disabling condition and often coincides with painful vertebral bone marrow lesions (“Modic changes”). We have recently shown that the bone marrow of Modic changes is fibrotic and that the maturation of myeloid cells is dysregulated. Cartilage breakdown products are extracellular matrix-derived DAMPs draining from the adjacent degenerated intervertebral disc into the bone marrow. They appear to be key in the pathogenesis of Modic changes. In this project we investigate the global mechanism how DAMPs modulate hematopoietic and mesenchymal stem cell lineage choice, how this causes fibrosis and dysmyelopoiesis, and we test novel therapeutics to inhibit this key process. Fresh human vertebral bone marrow aspirates will be used for this project. The project will be conducted at the new Balgrist Campus, a musculoskeletal research institution with research groups from UZH, ETH, and industry.
The goal of the project is to identify DAMPs that are key regulators of hematopoiesis and to test the efficacy of state-of-the-art molecular therapeutic approaches to modify these processes. MSC and HSPC from human bone marrow will be isolated, cultured, and stimulated with DAMPs. Their multilineage differentiation capacity will be quantified with colony-foming-units, histology, and qPCR. Pro-fibrotic activity will be quantified with qPCR, ELISA, and functional assays. The project will be supervised by Dr. Stefan Dudli (USZ) and Prof. Oliver Distler (USZ). Students interested in working with primary human tissue and with strong interests in stem cell regulation are encouraged to apply. The ideal candidate already has practical experience in cell culture and molecular biology. Tasks: 10% literature review, 40% cell culture, 40% analysis and data evaluation, 10% documentation.
The goal of the project is to identify DAMPs that are key regulators of hematopoiesis and to test the efficacy of state-of-the-art molecular therapeutic approaches to modify these processes. MSC and HSPC from human bone marrow will be isolated, cultured, and stimulated with DAMPs. Their multilineage differentiation capacity will be quantified with colony-foming-units, histology, and qPCR. Pro-fibrotic activity will be quantified with qPCR, ELISA, and functional assays. The project will be supervised by Dr. Stefan Dudli (USZ) and Prof. Oliver Distler (USZ). Students interested in working with primary human tissue and with strong interests in stem cell regulation are encouraged to apply. The ideal candidate already has practical experience in cell culture and molecular biology. Tasks: 10% literature review, 40% cell culture, 40% analysis and data evaluation, 10% documentation.
University Hospital Zurich,
Center for Experimental Rheumatology,
Balgrist Campus,
Stefan Dudli: stefan.dudli@usz.ch, +41 44 510 75 13,
Oliver Distler: oliver.distler@usz.ch
University Hospital Zurich, Center for Experimental Rheumatology, Balgrist Campus, Stefan Dudli: stefan.dudli@usz.ch, +41 44 510 75 13, Oliver Distler: oliver.distler@usz.ch