Publications de Ute Koch | EPFL Graph Search

Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs

Innate-like splenic marginal zone (MZ) B (MZB) cells play unique roles in immunity due to their rapid responsiveness to blood-borne microbes. How MZB cells integrate cell-extrinsic and -intrinsic processes to achieve accelerated responsiveness is unclear. ...

2025

Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation

Freddy Radtke, Ute Koch

A better understanding of the mechanisms regulating CD8+ T cell differentiation is essential to develop new strategies to fight infections and cancer. Using genetic mouse models and blocking antibodies, we uncovered cellular and molecular mechanisms by whi ...

ROCKEFELLER UNIV PRESS2025

Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis

Freddy Radtke, Ute Koch, Jialin Zhang, Soufiane Boumahdi

Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined f ...

ELSEVIER2023

Stroma-Driven Notch2 Signaling Controls Naive B Cell Fate By Regulating Microenvironmental Positioning within the Spleen

Freddy Radtke, Ute Koch

Amer Soc Hematology2023

Stromal Notch ligands foster lymphopenia-driven functional plasticity and homeostatic proliferation of naive B cells

Freddy Radtke, Ute Koch

In lymphopenic environments, secondary lymphoid organs regulate the size of B and T cell compartments by supporting the homeostatic proliferation of mature lymphocytes. The molecular mechanisms underlying these responses and their functional consequences r ...

AMER SOC CLINICAL INVESTIGATION INC2022

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL

Freddy Radtke, Ute Koch, Nadine Fournier, Marianne Nkosi, Christelle Dubey, Mateusz Waldemar Antoszewski, Tara Kimberly Sugrue, Giovanni Ciriello

NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape du ...

AMER SOC HEMATOLOGY2022

A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation

Freddy Radtke, Bart Deplancke, Ute Koch, Vincent Roland Julien Gardeux, Julie Marie Russeil, Jörn Pezoldt, Judith Franziska Kribelbauer, Riccardo Dainese, Daniel Alpern, Maria Litovchenko

Non-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. These molecularly coordinated regions are named "variable chromatin modules" (VCMs), providing a conceptual framework of h ...

Nature Portfolio2022

Notch signaling promotes disease initiation and progression in murine chronic lymphocytic leukemia

Freddy Radtke, Ute Koch, Jessica Sordet, Nadine Fournier, Marianne Nkosi, Delphine Maude Tardivon, Mateusz Waldemar Antoszewski

NOTCH1 gain-of-function mutations are recurrent in B-cell chronic lymphocytic leukemia (B-CLL), where they are associated with accelerated disease progression and refractoriness to chemotherapy. The specific role of NOTCH1 in the development and progressio ...

AMER SOC HEMATOLOGY2021

Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelia lineage in fetal thymus development

Freddy Radtke, Ute Koch, Dong Liu

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. Duri ...

2020

Pharmacological disruption of the Notch transcription factor complex

Freddy Radtke, Ute Koch, Nadine Fournier, Jelena Zaric, Rajwinder Lehal, Linlin Cao, Michele Vigolo

Notch pathway signaling is implicated in several human cancers. Aberrant activation and mutations of Notch signaling components are linked to tumor initiation, maintenance, and resistance to cancer therapy. Several strategies, such as monoclonal antibodies ...

National Academy of Sciences2020