
Our primary research interest lies in understanding how functional changes in niche cells upon aging or intermittent stress contribute to HSC maintenance, leukemogenesis, and functional degeneration in vivo. To achieve this, we employ a diverse array of in vitro and in vivo genetic and molecular models, with a current emphasis on factors secreted by stromal niche cells, such as the canonical Wnt-signaling inhibitors SFRP1 and WNT5A. Specifically, we investigate how stromal cells communicate with HSCs and LICs, which specific signals are exchanged, and how the intracellular processes affected by these signals, both in stroma to stem cell, as vice versa from stem cell to stroma. Our recent findings indicate that stromal cells regulate proteostasis and assembly of filamentous actin in HSCs and LICs—a process critical for key cellular functions, including migration, vesicle formation (endocytosis, exocytosis, autophagy), and cell division. Importantly, stress-induced functional degeneration of BM-MSCs is associated with osteopenia and osteoporosis, the symptoms of which can be reduced by therapeutically restoring cytoskeletal integrity and autophagy.
In addition, actin dynamics, particularly the formation of filamentous actin–based structures such as lamellipodia, filopodia, and invadopodia, is also a hallmark of aggressive and metastasizing tumor cells. As part of our research, we focus on osteosarcoma as a model of malignant BM-MSCs to study proteostasis and F-actin assembly as potential therapeutic targets in osteosarcoma metastasis using genetic and molecular approaches in both mouse models and human patient samples.
A key objective of our studies is to determine the significance of niche-regulated signaling pathways and explore their potential as therapeutic targets. Our findings may contribute to strategies for improving HSC engraftment and developing novel treatments for malignant diseases.
- Landspersky T, Stein M, Sacma M, Geuder J, Braitsch K, Jennifer Rivière, Hettler F, Romero Marquez S, Vilne B, Hameister E, Richter D, Schönhals E, Tuckermann J, Verbeek M, Herhaus P, Hecker JS, Bassermann F, Götze KS, Enard W, Geiger H, Oostendorp RAJ, Schreck C (2024). Targeting CDC42 reduces skeletal degeneration after hematopoietic stem cell transplantation. Blood advances . Oct 22;8(20):5400-5414. doi: 10.1182/bloodadvances.2024012879.
- Hettler F, Schreck C, Romero Marquez S, Engleitner T, Vilne B, Landspersky T, Weidner H, Hausinger R, Mishra R, Oellinger R, Rauner M, Naumann R, Peschel C, Bassermann F, Rad R, Istvanffy R, Oostendorp RAJ (2023). Osteoprogenitor SFRP1 prevents exhaustion of hematopoietic stem cells via PP2A-PR72/130-mediated regulation of p300. Haematologica, 108(2): 490-501. doi: 10.3324/haematol.2022.280760
- Landspersky T, Saçma M, Rivière J, Hecker JS, Hettler F, Hameister E, Brandstetter K, Istvánffy R, Romero Marquez S, Ludwig R, Götz M, Buck M, Wolf M, Schiemann M, Ruland J, Strunk D, Shimamura A, Myers K, Yamaguchi TP, Kieslinger M, Leonhardt H, Bassermann F, Götze KS, Geiger H, Schreck C, Oostendorp RAJ (2022). Autophagy in mesenchymal progenitors protects mice against bone marrow failure after severe intermittent stress. Blood, 139(5): 690-703. doi: 10.1182/blood.2021011775
- Scharler C, Poupardin R, Ebner-Peking P, Wolf M, Schreck C, Brachtl G, Cronemberger Andrade A, Krisch L, Daheron L, Schallmoser K, Jürchott K, Küchler J, Stachelscheid H, Volk HD, Oostendorp RAJ, Strunk D (2022). Extra-hematopoietic immunomodulatory role of the guanine-exchange factor DOCK2. Commun Biol., 15;5(1):1246. https://doi.org/10.1038/s42003-022-04078-1
- Weickert MT, Hecker JS, Buck MC, Schreck C, Rivière J, Schiemann M, Schallmoser K, Bassermann F, Strunk D, Oostendorp RAJ, Götze KS (2021). Bone marrow stromal cells from MDS and AML patients show increased adipogenic potential with reduced Delta-like-1 expression. Sci Rep. 11(1): 5944. doi: 10.1038/s41598-021-85122-8.
- Romero Marquez S, Hettler F, Hausinger R, Schreck C, Landspersky T, Henkel L, Angerpointner C, Demir IE, Schiemann M, Bassermann F, Götze KS, Istvánffy R, Oostendorp RAJ (2021). Secreted factors from mouse embryonic fibroblasts maintain repopulating function of single cultured hematopoietic stem cells. Haematologica. 106(10):2633-2640. DOI: 10.3324/haematol.2020.249102
- Fröbel J, Landspersky T, Percin G, Schreck C, Rahmig S, Ori A, Nowak D, Essers M, Waskow C, Oostendorp RAJ. (2021). The Hematopoietic Bone Marrow Niche Ecosystem Front Cell Dev Biol. 2021 Jul 22;9:705410. https://doi.org/10.3389/fcell.2021.705410
- Schreck C, Istvánffy R, Ziegenhain C, Sippenauer T, Ruf F, Henkel L, Gärtner F, Vieth B, Florian MC,Mende N, Taubenberger A, Prendergast Á, Wagner A, Pagel C, Grziwok S, Götze KS, Guck J, Dean DC, Massberg S, Essers M, Waskow C, Geiger H, Schiemann M, Peschel C, Enard W, Oostendorp RA (2017). Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells. J Exp Med, 214(1):165-181. https://doi.org/10.1084/jem.20151414
- Ruf F, Schreck C, Wagner A, Grziwok S, Pagel C, Romero S, Kieslinger M, Shimono A, Peschel C, Götze KS, Istvanffy R, Oostendorp RAJ (2016). Loss of Sfrp2 in the niche amplifies stress-induced cellular responses, and impairs the in vivo regeneration of the hematopoietic stem cell pool. Stem Cells. 34(9):2381-92. https://doi.org/10.1002/stem.2416
- Schreck C, Bock F, Grziwok S, Oostendorp RA, Istvánffy R (2014). Regulation of hematopoiesis by activators and inhibitors of Wnt signaling from the niche. Ann N Y Acad Sci, 1310:32-43. https://doi.org/10.1111/nyas.12384
Visit full publication list, ORCID or GEPRIS Profile.
We are looking for Master students (Biology and Molecular Biotechnology) for internships and Master Thesis Research. Please send and Email with your application.
TUM Master of Science in Biology or Molecular Biotechnology
Lecturers: Apl. Prof. Dr. Robert Oostendorp and Dr. Christina Schreck
- Lecture and Seminar series:
- Blood-forming stem cells as a model for somatic stem cells (TUM Module Nr.: ME2759)
- Research Internships:
- Hematopoietic stem cells (TUM WZW Module Nr.: WZme2677, also for LMU students)
- Scientific Project Planning (WPP)
- Supervision of Master Theses
DFG- Deutsche Forschungsgemeinschaft (GEPRIS):
https://gepris.dfg.de/gepris/person/1799068
Previous grants from:
- Bavarian Department of Environment, Health, and Consumerinterest (Acronym: STEMMAT);
- European Community (Acronym: GenoStem)
- José Carreras Leukämie-Stiftung
- Wilhelm Sander Stiftung
- TUM School of Computation, Information and Technology (GSISH)
- TUM School of Medicine and Health (Clinical Research Committee)