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Articles by Daniel Hübschmann
Author Correction: A kinetics-based model of haematopoiesis reveals extrinsic regulation of skewed lineage output from stem cells
Correction to: Nature Cell Biology https://doi.org/10.1038/s41556-026-01958-0, published online 25 May 2026. In the version of the article initially published, in the source data for Extended Data Fig.5a, a copy–paste error meant that for one recipient mouse, the peripheral blood cell values at the 20 week time point had been duplicated as the 24 week time point when the latter should have been blank.
A kinetics-based model of haematopoiesis reveals extrinsic regulation of skewed lineage output from stem cells
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Abstract Haematopoietic stem cells (HSCs) display extensive molecular and functional heterogeneity. However, a cohesive model that explains the relationship and biological relevance of these diverse HSC states remains elusive.
By Esther Rodriguez-Correa, Florian Grünschläger, Tamar Nizharadze, Natasha Anstee, Jude Al-Sabah, Vojtech Kumpost, Anastasia Sedlmeier, Congxin Li, Melanie Ball, Ian Ghezzi, Susanne Lux, Pablo Hernández-Malmierca, Dominik Vonficht, Marta Lopez-Osias, Daniel Fernández-Pérez, Anna Mathioudaki, Judith B. Zaugg, Alejo E. Rodriguez-Fraticelli, Ralf Mikut, Andreas Trumpp, Thomas Hofer, Daniel Hübschmann, Simon J. Haas, Michael D. Milsom, Foteini Fotopoulou, Jeyan Jayarajan, Julia Knoch, Megan Druce, Kleo Aurich, Marleen Büchler-Schäff, Julius Gräsel, Elvira González-Saiz
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Nature
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Glucocorticoids induce a phagocytic C1Q+ macrophage phenotype primed for IFNγ-dependent CXCL9 secretion
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Abstract Glucocorticoids are an emerging component of the tumor microenvironment and play a multifaceted role in modulating immune responses. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by systemic cortisol excess in ~ 60% of cases. Responses to immune checkpoint inhibitors (ICI) in patients with ACC are variable, and currently, no reliable biomarkers exist to predict therapeutic outcomes.
By Alexandra Triebig, Tanja Maier, Paul Schwarzlmueller, Sena Atici, Vasileios Chortis, Kleiton S. Borges, David Breault, Claudio Ribeiro, Adrian Gottschlich, Laura-Sophie Landwehr, Nicole Bechmann, Mirko Peitzsch, Nagarajan Paramasivam, Sebastian Theurich, Stefan Fröhling, Hanno Glimm, Daniel Hübschmann, Martin Fassnacht, Martin Reincke, Isabel Weigand, Matthias Kroiss, Martin E. Kirmaier, Jose Pedro Friedmann-Angeli
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Nature
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Multi-layered molecular profiling informs the diagnosis and targeted therapy of desmoplastic small round cell tumor
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Abstract Desmoplastic small round cell tumor (DSRCT) is an ultra-rare sarcoma with limited treatment options. Here, we show that comprehensive molecular profiling informs diagnosis and individualized therapy in this disease. We report the results of whole-genome/exome, transcriptome, and DNA methylome analyses performed in 30 refractory DSRCT patients, complemented by (phospho)proteomic profiling in nine, within a nationwide precision oncology program.
By Marcus Renner, Nagarajan Paramasivam, Christoph E. Heilig, Annika Schneider, Jennifer Hüllein, Barbara Hutter, Cihan Erkut, Andreas Mock, Eva I. Krieghoff-Henning, Amirhossein Sakhteman, Matthew The, Tony Prinz, Panna Lajer, Katja Beck, Bettina Beuthien-Baumann, Leonidas Apostolidis, Sebastian Bauer, Melanie Boerries, Christian H. Brandts, Damian T. Rieke, Thomas Kindler, Frederick Klauschen, Klaus Schulze-Osthoff, Richard F. Schlenk, Guy Berchem, Michael Allgäuer, Gunhild Mechtersheimer, Albrecht Stenzinger, Daniel B. Lipka, Matthias Schlesner, Bernhard Kuster, Arne Jahn, Evelin Schröck, Christoph Heining, Peter Horak, Simon Kreutzfeldt, Daniel Hübschmann, Wolfgang Hartmann, Hanno Glimm, Stefan Fröhling, Małgorzata Oleś, Caroline Modugno, Catherine Herremans, Cecilia B. Jensen, Annika Baude-Müller, Maria-Veronica Teleanu
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Nature
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Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma
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Abstract Lymph node (LN) function requires the organization of cells into higher-order spatial units. However, the principles governing LN architecture in health and disease remain poorly understood. Here, we used single-cell and spatial mapping to investigate the mechanisms directing immune cell organization in human LNs and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL).
By Felix Czernilofsky, Anna Mathioudaki, Lea Jopp-Saile, Raphael Lutz, Dominik Vonficht, Xi Wang, Tobias Roider, Marc-Andrea Baertsch, Michael Grau, Donnacha Fitzgerald, Jan Kosla, Nora Liebers, Peter-Martin Bruch, Diana Ordoñez-Rueda, Alexander Brobeil, Gunhild Mechtersheimer, Caroline Pabst, Carsten Müller-Tidow, Andreas Trumpp, Frank Neumann, Mathias Heikenwalder, Vladimir Benes, Wolfgang Huber, Jörg H. W. Distler, Georg Lenz, Hans Binder, Reiner Siebert, Garry P. Nolan, Moritz Gerstung, Judith B. Zaugg, Daniel Hübschmann, Simon J. Haas, Sascha Dietrich, Christina Schniederjohann, Harald Voehringer, Claus Rodemer, Henry Löffler-Wirth, Johannes Mammen, Marc Seifert
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Nature
Verified
Multimodal plasma and urinary cell-free DNA profiling improves risk stratification in newly diagnosed prostate cancer - npj Precision Oncology
Abstract Prostate cancer (PCa) is a heterogeneous disease, impeding early detection and risk stratification.
The Knowledge Connector decision support system for multiomics-based precision oncology - Nature Communications
Abstract Precision cancer medicine aims to improve patient outcomes by providing individually tailored recommendations for clinical management based on the evaluation of biological disease profiles in multidisciplinary molecular tumor boards (MTBs). The quality of MTB decisions depends on the comprehensive, reliable, and reproducible interpretation of increasingly complex molecular data.
Ultra-high-scale cytometry-based cellular interaction mapping - Nature Methods
Abstract Cellular interactions are of fundamental importance, orchestrating organismal development, tissue homeostasis and immunity. Recently, powerful methods that use single-cell genomic technologies to dissect physically interacting cells have been developed. However, these approaches are characterized by low cellular throughput, long processing times and high costs and are typically restricted to predefined cell types.
A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer - Nature Communications
Abstract Salivary gland cancers are rare, diverse malignancies characterized by poor response to immunotherapy. The tumor immune environment in these cancers remains poorly understood. To address this, we perform an integrative analysis of the tumor immune microenvironment in a large cohort of advanced salivary gland cancer samples. Most tumors exhibit low immune activity with limited immune cell infiltration.
Subgrouping germinal center-derived B-cell lymphomas based on machine learning-deduced DNA methylation modules - Leukemia
To the Editor: Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the most common lymphomas, both exhibiting features of germinal center-derived B-cells (gcBCs). DLBCL can arise de novo or through transformation of a low-grade lymphoma like FL. FL and DLBCL are heterogeneous with regard to clinical outcome as well as morphologic, immunophenotypic, genetic, transcriptomic and other biological aspects [1].
Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology - npj Precision Oncology
Abstract Precision oncology offers new cancer treatment options, yet sequencing methods vary in type and scope. In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020.
Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy - Nature Communications
Abstract The long-term consequences of cancer and its therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we present an in-depth characterization of the bone marrow immune ecosystem of multiple myeloma long-term survivors, from initial diagnosis up to 17 years following a single therapy line and cancer-free survival.
Innovation in cancer pharmacotherapy through integrative consideration of germline and tumor genomes
Abstract Precision cancer medicine is widely established, and numerous molecularly targeted drugs for various tumor entities are approved or in development. Personalized pharmacotherapy in oncology has so far been based primarily on tumor characteristics, e.g., somatic mutations. However, the response to drug treatment also depends on pharmacological processes summarized under the term ADME (absorption, distribution, metabolism, and excretion).
Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions - Nature Communications
Abstract Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors.
NCT/DKFZ MASTER handbook of interpreting whole-genome, transcriptome, and methylome data for precision oncology - npj Precision Oncology
Abstract Analysis of selected cancer genes has become an important tool in precision oncology but cannot fully capture the molecular features and, most importantly, vulnerabilities of individual tumors. Observational and interventional studies have shown that decision-making based on comprehensive molecular characterization adds significant clinical value.
Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial - Nature Cancer
Abstract Ex vivo drug response profiling is a powerful tool to study genotype–drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial, NCT03488641). The primary endpoint to provide drug response profiling reports within 7 d was met in 91% of all study participants (N = 80).
Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity - Nature Communications
Abstract The benefit of molecularly-informed therapies in cancer of unknown primary (CUP) is unclear. Here, we use comprehensive molecular characterization by whole genome/exome, transcriptome and methylome analysis in 70 CUP patients to reveal substantial mutational heterogeneity with TP53, MUC16, KRAS, LRP1B and CSMD3 being the most frequently mutated known cancer-related genes. The most common fusion partner is FGFR2, the most common focal homozygous deletion affects CDKN2A.
The genomic and transcriptional landscape of primary central nervous system lymphoma - Nature Communications
Abstract Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS.
Improve consensus partitioning via a hierarchical procedure
Abstract Consensus partitioning is an unsupervised method widely used in high throughput data analysis for revealing subgroups and assigns stability for the classification. However, standard consensus partitioning procedures are weak to identify large numbers of stable subgroups. There are two main issues. 1. Subgroups with small differences are difficult to separate if they are simultaneously detected with subgroups with large differences. And 2.
Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas
Abstract B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR.
Integrative genomic and transcriptomic analysis of leiomyosarcoma
Abstract External IDs PubMed 29321523
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