A5062422556- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Protein Degradation and Inhibitors
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- Single-cell and spatial transcriptomics
- Reproductive System and Pregnancy
- Cell Adhesion Molecules Research
- Hemoglobinopathies and Related Disorders
- Neutropenia and Cancer Infections
- Epigenetics and DNA Methylation
- Virus-based gene therapy research
- Extracellular vesicles in disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
Heidelberg University
2019-2025
German Red Cross
2011-2025
DKFZ-ZMBH Alliance
2019-2025
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2022-2025
German Cancer Research Center
2019-2025
Washington University in St. Louis
2015-2024
TRUMPF (Germany)
2023
Deutschen Konsortium für Translationale Krebsforschung
2022
Goethe University Frankfurt
2011-2019
DRK-Blutspendedienst Baden-Württemberg - Hessen
2013
Mechanisms behind how the immune system signals to brain in response systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically hematopoietic lineage a reporter background display recombination and marker gene expression Purkinje neurons. Here we show that reportergene neurons is caused by intercellular transfer of functional messenger RNA from cells into absence cell fusion. In vitro purified secreted extracellular vesicles (EVs) blood contain...
The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data identify predictors 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, differentiation was not predictive our patient cohort. We identified leukemic...
Abstract Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance circulation, robust CTC expansion protocols are urgently needed effectively study disease progression and therapy responses. Here we present establishment long-term CTC-derived organoids from female metastatic Multiomics analysis along preclinical modeling xenografts identified neuregulin 1 (NRG1)–ERBB2 receptor tyrosine kinase 3 ( ERBB3 /HER3)...
Donor blood saves lives, yet the potential impact of recurrent large-volume phlebotomy on donor health and hematopoietic stem cells (HSCs) remains largely unexplored. In our study, we conducted a comprehensive screening 217 older male volunteer donors with history extensive donation (>100 life-time donations) to investigate phenomenon clonal hematopoiesis (CH). No significant difference in overall incidence CH was found frequent (FD) compared sporadic (<10 donations, 212...
This 21-color flow cytometry-based OMIP 1 enables simultaneous quantification of monocytes, basophils, granulocytes, dendritic cells, natural killer B and all well-defined T helper cell subsets in the human peripheral blood (Table 1). panel captures major phenotypes described NIH Human Immunology Project 2, 3 with additional markers for deep analysis 4. We specifically designed this from patients involved our clinical trials novel agents treatment graft versus host disease (GVHD) after...
Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic cell transplantation. Pharmacologically enforced egress from BM, or mobilization, been achieved by directly indirectly targeting CXCL12/CXCR4 axis. Shortcomings standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone in combination with only approved CXCR4 antagonist, Plerixafor, continue to fuel quest new agents. Using Protein...
Abstract Background Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel quest for alternatives. We herein report results a Phase I dose escalation trial comparing mobilization with peptidic CXCR4 antagonist POL6326 (balixafortide) vs. G-CSF. Methods Healthy male volunteer donors documented average response to received, following ≥6 weeks wash-out, 1–2 h infusion 500–2500 µg/kg balixafortide. Safety, tolerability, pharmacokinetics...
Mobilized peripheral blood has become the primary source of hematopoietic stem and progenitor cells (HSPCs) for cell transplantation, with a 5-day course granulocyte colony-stimulating factor (G-CSF) as most common regimen used HSPC mobilization. The CXCR4 inhibitor plerixafor is more rapid mobilizer, yet not potent enough when single agent, thus emphasizing need faster acting agents predictable mobilization responses fewer side effects. We sought to improve transplantation by developing new...
Background aimsImmunomagnetic enrichment of CD34+ hematopoietic "stem" cells (HSCs) using paramagnetic nanobead coupled CD34 antibody and immunomagnetic extraction with the CliniMACS plus system is standard approach to generating T-cell-depleted stem cell grafts. Their clinical beneficence in selected indications established. Even though grafts are typically given context a severely immunosuppressive conditioning anti-thymocyte globulin or similar, degree T-cell depletion appears affect...
Abstract Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on mitigation GvHD by AzaC, instead focusing generation suppressive Tregs (CD4+CD25+FOXP3+) through vivo conversion alloreactive donor effectors (Teffs; CD4+CD25−FOXP3−) direct antiproliferative effects...
Enforced egress of hematopoietic stem cells (HSCs) out the bone marrow (BM) into peripheral circulation, termed mobilization, has come a long way since its discovery over four decades ago. Mobilization research continues to be driven by need optimize regimen currently available in clinic with regard pharmacokinetic and pharmacodynamic profile, costs, donor convenience. In this review, we describe most recent findings field how anticipate them affect development mobilization strategies...
Mesenchymal stromal cells are key components of hematopoietic niches in the bone marrow. Here we abrogated transforming growth factor β (TGF-β) signaling mesenchymal stem/progenitor (MSPCs) by deleting Tgfbr2 using a doxycycline-repressible Sp7 (osterix)-Cre transgene. We show that loss TGF-β during fetal development results marked expansion CXCL12-abundant reticular (CAR) and adipocytes marrow, while osteoblasts significantly reduced. These alterations associated with significant defects...
<p>Bcl-2 family gene expression in LSCs predicts vitro response to HMA/VEN</p>
<p>Subpopulation specific Bcl-2 family levels and time on HMA/Venetoclax</p>
<p>Transcriptomic and functional characterization of LSC-like cells</p>
<p>Cell line sensitivity and additional patient data</p>
<p>Subpopulation specific Bcl-2 family levels and response to HMA/Venetoclax</p>
<p>Comparison of MAC-Score and BH-3 profiling based response prediction</p>