Staehle Lab
The Staehle Lab studies the molecular mechanisms underlying myeloid malignancies, including acute myeloid leukemia and myeloproliferative neoplasm. As part of the Section of Molecular Hematology, we focus on identifying disease-driving signaling pathways and aim to translate our mechanistic insights into novel therapeutic strategies. We use a wide-range of molecular and cellular techniques including RNA-seq, ATAC-seq, ChIP-seq, multi-color flow cytometry, and spatial imaging. Having built strong collaborations within the TARGET MPN research unit, we also conduct projects employing single-cell and Mass Spectometry techniques. Together, these techniques enable integrative studies in both patient-derived samples and mouse models.
Project 1 - Epigenetic profiling of myeloid malignancies
One focus of our lab is to characterize epigenetic regulation in acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN). In particular, we investigate the therapeutic potential of histone demethylases. While preclinical studies of the histone demethylase LSD1 have paved the way for clinical applications, its functional mechanisms remain incompletely understood, which is a key focus of our research (Cell Death & Disease 2025). In addition, we explore the function and therapeutic potential of JMJD-domain containing histone demethylases (PlosOne 2020, Leukemia 2023).
Project 2 - Post-Translational Regulators in myeloid malignancies
The transcription factor NFE2 plays a key role in the pathophysiology of myeloproliferative neoplasms (MPN) and in the progression to acute myeloid leukemia (AML). Approximately 4–9% of MPN patients carry NFE2 mutations that enhance transcriptional activation of the remaining wild-type allele. However, the mechanisms underlying this increased NFE2 activity are not fully understood. In this project, we investigate how the E3 ubiquitin ligase ITCH, which interacts with NFE2, posttranslationally regulates both wild-type and mutant NFE2 (IJMS 2025).
Project 3 - Regulation of oncogenic signaling pathways in myeloid malignancies
The adapter protein LNK negatively regulates oncogenic signaling pathways such as JAK2, c-KIT, and FLT3. Mutations that impair LNK function lead to pathway activation and increased proliferation in myeloid malignancies. However, the mechanisms underlying these mutations are not yet fully understood. This project aims to characterize LNK and its mutants to uncover their functional impact and therapeutic potential.
TEAM
Principal Investigator
Dr. med. Felix Staehle
Telefon +49 (0) 761 270-71800
Telefax +49 (0) 761 270-96-71910
hans.felix.staehle@uniklinik-freiburg.de
Zentrum Translationale Zellforschung (ZTZ)
Breisacher Str. 115
D- 79106 Freiburg
cand. med. Anja Müller
Telefon +49 (0) 761 270-71811
anja.mueller@uniklinik-freiburg.de
Ph.D cand. Jana Schulze
Telefon +49 (0) 761 270-71811
jana.schulze@uniklinik-freiburg.de
cand. med. Franziska Zell
Telefon +49 (0) 761 270-71811
franziska.zell@uniklinik-freiburg.de
cand. med. Mirjam Höneß
Telefon +49 (0) 761 270-71811
mirjam.hoeness@uniklinik-freiburg.de
Publications
Hoeness ME, Zell F, Basu T, Gellrich K, Gründer A, Schulze J, Müller A, Eble P, Koellerer C, Staehle AM, Bojtine Kovacs S, Pahl HL, Staehle HF. NFE2 Truncation Mutants Protect Wild-Type NFE2 from ITCH-Dependent Degradation. Int J Mol Sci. 2025 Dec 16;26(24):12112. doi: 10.3390/ijms262412112. PMID: 41465537; PMCID: PMC12733253.
Staehle HF, Koellerer C, Staehle AM, Schulze J, Eble P, Müller A, Zell F, Müller JM, Perner F, Attia A, Mallm JP, Pozdnyakova O, Rippe K, Brors B, Feuerbach L, Imbusch CD, Metzger E, Schüle R, Pahl HL, Jutzi JS. Lysine-specific demethylase 1 regulates hematopoietic stem cell expansion and myeloid cell differentiation. Cell Death Dis. 2025 Aug 15;16(1):619. doi: 10.1038/s41419-025-07951-z. PMID: 40813574; PMCID: PMC12354751.
Schmidt D, Endres C, Hoefflin R, Andrieux G, Zwick M, Karantzelis N, Staehle HF, Vinnakota JM, Duquesne S, Mozaffari Jovein M, Pfeifer D, Becker H, Blazar BR, Zähringer A, Duyster J, Brummer T, Boerries M, Baumeister J, Shoumariyeh K, Li J, Green AR, Heidel FH, Tirosh I, Pahl HL, Leimkühler N, Köhler N, de Toledo MAS, Koschmieder S, Zeiser R. Oncogenic Calreticulin Induces Immune Escape by Stimulating TGFβ Expression and Regulatory T-cell Expansion in the Bone Marrow Microenvironment. Cancer Res. 2024 Sep 16;84(18):2985-3003. doi: 10.1158/0008-5472.CAN-23-3553. PMID: 38885318; PMCID: PMC11405138.
Wollborn J, Zhang Z, Gaa J, Gentner M, Hausmann C, Saenger F, Weise K, Justice S, Funk JL, Staehle HF, Thomas M, Bruno RR, Saravi B, Friess JO, Marx M, Buerkle H, Trummer G, Muehlschlegel JD, Reker D, Goebel U, Ulbrich F. Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery. Ann Intensive Care. 2023 Aug 8;13(1):70. doi: 10.1186/s13613-023-01165-2. PMID: 37552379; PMCID: PMC10409979.
Staehle AM, Peeken JC, Vladimirov G, Hoeness ME, Bojtine Kovacs S, Karantzelis N, Gruender A, Koellerer C, Jutzi JS, Pahl HL, Staehle HF. The histone demethylase JMJD2C constitutes a novel NFE2 target gene that is required for the survival of JAK2V617F mutated cells. Leukemia. 2023 Apr;37(4):919-923. doi: 10.1038/s41375-023-01826-y. Epub 2023 Jan 28. PMID: 36709354; PMCID: PMC10079541.
Staehle HF, Pahl HL, Jutzi JS. The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies. Biomolecules. 2021 Dec 20;11(12):1911. doi: 10.3390/biom11121911. PMID: 34944554; PMCID: PMC8699298.
Wollborn J, Hassenzahl LO, Reker D, Staehle HF, Omlor AM, Baar W, Kaufmann KB, Ulbrich F, Wunder C, Utzolino S, Buerkle H, Kalbhenn J, Heinrich S, Goebel U. Diagnosing capillary leak in critically ill patients: development of an innovative scoring instrument for non-invasive detection. Ann Intensive Care. 2021 Dec 15;11(1):175. doi: 10.1186/s13613-021-00965-8. PMID: 34910264; PMCID: PMC8674404.
Staehle HF, Heinemann J, Gruender A, Omlor AM, Pahl HL, Jutzi JS. Jmjd1c is dispensable for healthy adult hematopoiesis and Jak2V617F-driven myeloproliferative disease initiation in mice. PLoS One. 2020 Feb 4;15(2):e0228362. doi: 10.1371/journal.pone.0228362. PMID: 32017785; PMCID: PMC6999878.
Kaufmann KB, Heinrich S, Staehle HF, Bogatyreva L, Buerkle H, Goebel U. Perioperative cytokine profile during lung surgery predicts patients at risk for postoperative complications-A prospective, clinical study. PLoS One. 2018 Jul 3;13(7):e0199807. doi: 10.1371/journal.pone.0199807. PMID: 29969473; PMCID: PMC6029786.
Jutzi JS, Kleppe M, Dias J, Staehle HF, Shank K, Teruya-Feldstein J, Gambheer SMM, Dierks C, Rienhoff HY Jr, Levine RL, Pahl HL. LSD1 Inhibition Prolongs Survival in Mouse Models of MPN by Selectively Targeting the Disease Clone. Hemasphere. 2018 Jun 8;2(3):e54. doi: 10.1097/HS9.0000000000000054. PMID: 31723778; PMCID: PMC6745991.
Peeken JC, Jutzi JS, Wehrle J, Koellerer C, Staehle HF, Becker H, Schoenwandt E, Seeger TS, Schanne DH, Gothwal M, Ott CJ, Gründer A, Pahl HL. Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms. Blood. 2018 May 3;131(18):2065-2073. doi: 10.1182/blood-2017-10-810622. Epub 2018 Mar 8. PMID: 29519804; PMCID: PMC5934799.
Awards
2025-Present Fellowship in the DGIM-funded Clinician Scientists Program
2022-Present EKFS project funding: “Combined knockdown of histone demethylases in MPN”
2021-2025 Fellowship in the EKFS-funded EXCEL Clinician Scientists Program
2020-2021 Fellowship in the SUCCESS Clinician Scientists Program
2015-2016 Fellowship in the EKFS-funded MOTI-VATE Doctoral Program
Cooperations
Internal cooperations
Prof. Dr. Heike L. Pahl (Klinik für Innere Medizin I)
Prof. Dr. Robert Zeiser (Klinik für Innere Medizin I)
Prof. Dr. Heiko Becker (Klinik für Innere Medizin I)
Prof. Dr. Michael Lübbert (Klinik für Innere Medizin I)
Dr. Khalid Shoumariyeh (Klinik für Innere Medizin I)
Prof. Dr. Marc Timmers (Deparment Urologie)
External cooperations
Dr. Dr. Jonas Jutzi (Brigham and Women's Hospital, Boston, USA)
Dr. Jakob Wollborn (Brigham and Women's Hospital, Boston, USA)
Prof. Dr. Ulrich Göbel (St. Franziskus Hospital, Münster, Germany)
Prof. Dr. Christoph Plass (DKFZ, Heidelberg, Germany)
Target MPN Research Unit
Dr. Ashok Kumar Jayavelu (Hopp Children’s Cancer Center, Heidelberg, Germany)
Dr. Florian Perner (Medical School Hannover (MHH), Hannover, Germany)
Univ.-Prof. Dr. med. Steffen Koschmieder (University Hospital RWTH Aachen, Germany)
Dr. Szymanski de Toledo (University Hospital RWTH Aachen, Germany)