Hematopoiesis is a highly regulated and complex process within the bone marrow that ensures adequate blood cell production throughout life. The process of blood and immune cell production is tightly regulated by cells of the bone marrow microenvironment. Intimate cross-talk between hematopoietic cells and mesenchymal stromal cells, osteoblasts, adipocytes, and endothelial cells orchestrates the proper responses to stress, infection, and blood loss. Disruption of these processes as well as the occurrence of somatic mutations in hematopoietic stem cells (termed clonal hematopoiesis, CH) during aging contribute to the development of clonal stem cell disorders such as myelodysplastic neoplasms (MDS) and acute myeloid leukemias (AML). We aim to understand the fundamental biological processes underlying normal and malignant hematopoiesis in the aging bone marrow and translate this knowledge to improve patient outcomes through novel rational therapies.

Our lab focuses on understanding clonal stem cell disorders, particularly the progression from clonal hematopoiesis and clonal cytopenias (CCUS) to MDS and AML. We study the interactions between hematopoietic stem cells (HSCs), immune cells, and niche cells within the bone marrow. Using primary human bone marrow samples from our well-annotated tissue repository, we employ advanced techniques like single-cell multiomics, CRISPR/Cas9 genetic engineering, stem cell assays, and multiparameter flow cytometry. Our goal is to understand the mechanisms by which CH progresses to overt myeloid malignacy and to uncover critical dependencies within the bone marrow microenvironment in both premalignant and malignant states that can be targeted for disease intervention or prevention. 

Our projects are funded by the Horizon 2020 Marie Curie Interactive Training Network (INTERCEPT-MDS), the German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung, DKTK), the Bavarian Center for Cancer Research (BZKF), and an unrestricted grant from BMS. We have close collaborations with researchers at the Department of Artificial Intelligence at the Helmholtz Institute for computational modeling of stem cell hierarchies in CH and MDS, with biobam in Valencia for bioinformatics analyses of scRNA sequencing, with the José Carreras Research Institute in Barcelona and with researchers within the European MDS network and German CH working group. 

• Winter S, Götze KS, Hecker JS, Metzeler KH, Guezguez B, Woods K, Medyouf H, Schäffer A, Schmitz M, Wehner R, Glauche I, Roeder I, Rauner M, Hofbauer LC, Platzbecker U. Clonal hematopoiesis and its impact on the aging osteo-hematopoietic niche. Leukemia. 2024 May;38(5):936-946. doi: 10.1038/s41375-024-02226-6. Epub 2024 Mar 21. PMID: 38514772; PMCID: PMC11073997.
• Götze KS. Flipping the switch in the stem cell niche. Blood. 2023 Aug 3;142(5):404-406. doi: 10.1182/blood.2023021286. PMID: 37535369.
• Buck MC*, Bast L*, Hecker JS, Rivière J, Rothenberg-Thurley M, Vogel L, Wang D, Andrä I, Theis FJ, Bassermann F, Metzeler KH, Oostendorp RAJ, Marr C, Götze KS. Progressive disruption of hematopoietic architecture from clonal hematopoiesis to MDS. iScience. 2023 Jul 10;26(8):107328. doi: 10.1016/j.isci.2023.107328. PMID: 37520699; PMCID: PMC10382887.
• Rivière J, Hock J, Buck MC, Hecker JS, Götze KS, van der Garde M. Choosing the source of healthy controls for studies on myeloid malignancies: all bone marrow cells are created equal, but some are more equal than others. Stem Cell Res Ther. 2023 Mar 8;14(1):36. doi: 10.1186/s13287-023-03257-z. PMID: 36882822; PMCID: PMC9993599.
• Hartmann L*, Hecker JS*, Rothenberg-Thurley M, Rivière J, …, Götze KS*, Metzeler KH*. Compartment-specific mutational landscape of clonal hematopoiesis. Leukemia. 2022 Sep 21. doi: 10.1038/s41375-022-01700-3. Epub ahead of print. PMID: 36131041.
• Braitsch K*, Schmalbrock LK*, …, Götze KS*, Rieger K*. Genotype and Intensive Pretreatment Influence Outcome of Acute Myeloid Leukemia Patients Treated With Venetoclax in Combination With Hypomethylating Agents or Low-dose Cytarabine: "Real World" Data From Germany. Hemasphere. 2022 Aug 9;6(9):e759. doi: 10.1097/HS9.0000000000000759. PMID: 35966764
• Hecker JS*, Hartmann L*, Rivière J, Buck MC, van der Garde M, …, Metzeler KH*, Götze KS*. CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease. Blood. 2021 Nov 4;138(18):1727-1732. doi: 10.1182/blood.2020010163. PMID: 34139005.
• Götze KS, Lengerke C. Bedeutung der klonalen Hämatopoese für hämatologische Neoplasien [Importance of clonal hematopoiesis for hematologic neoplasms]. Inn Med (Heidelb). 2022 Nov;63(11):1107-1114. German. doi: 10.1007/s00108-022-01401-0. Epub 2022 Sep 20. PMID: 36125513.
• Bast L*, Buck MC*, Hecker JS, Oostendorp RAJ, Götze KS*, Marr C*. Computational modeling of stem and progenitor cell kinetics identifies plausible hematopoietic lineage hierarchies. iScience. 2021 Jan 29;24(2):102120. doi: 10.1016/j.isci.2021.102120. PMID: 33665548
• Diesch J, Le Pannérer MM, Winkler R, Casquero R, Muhar M, van der Garde M, …, Götze KS, Buschbeck M. Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis. Nat Commun. 2021 Oct 18;12(1):6060. doi: 10.1038/s41467-021-26258-z. PMID: 34663789

We invite PhD candidates interested in translational cancer research, particularly in areas such as hematopoiesis, leukemia, and stem cell research, to join our team. Ideal candidates should have experience in stem cell assays, flow cytometry, RNA sequencing, bioinformatics, genomics, or computational biology.

For inquiries or to express interest in joining our group, please contact Prof. Dr. Götze.

• ERC Horizon 2020 Marie Curie Interactive Training Network (https://intercept-mds.eu)
• Deutsches Konsortium für Translationale Krebsforschung (DKTK), Joint funding CHOICE
• Wilko Weichert Grant 2024
• Bayerisches Zentrum für Krebsforschung (BZKF), Translationsgruppe AML
• DFG, SFB 1243 (completed)
• DJCLS grant (completed)