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MicroRNA 21 is a novel oncogene in Notch1-driven acute lymphoblastic T cell leukemia

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Method Development towards Orthogonal Electrophile Delivery

Lingxi Wang

Redox signaling events mediated by reactive electrophilic species (RES) are key players in several cellular processes. However, the studies on RES have been challenging due to their high reactivity towards numerous nucleophilic groups present in the cells ...

EPFL2021

Nearly all the cells of an organism share the same DNA sequence or genome, and yet they show different phenotypes and carry out different functions. This diversity is made possible by a verity of molecular modifications acting on the DNA sequence that coll ...

EPFL2020

Notch Signaling - a Booster of Chronic Lymphocytic Leukemia During Initiation and Disease Progression

Delphine Maude Tardivon

Chronic lymphocytic leukemia (CLL) is a B cell malignancy and represents the most common leukemia in adults within the Western world. This disease mainly affects the elderly, with a median age of diagnosis over 70. The disease course is highly variable amo ...

EPFL2020

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 ...

NATL ACAD SCIENCES2020

B-cell non-Hodgkin lymphomas (B-NHLs) are a heterogeneous group of tumors deriving from the malignant transformation of B cells. The two most common B-NHL subtypes are follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), which account togeth ...

EPFL2019

Modeling hematopoietic stem cell dynamics in bioengineered niches

Sonja Giger

Bone marrow transplantation is a well-established medical procedure for the treatment of various hematologic diseases. However, the relatively low number of hematopoietic stem cells (HSCs) that can be harvested, especially from umbilical cord blood, limits ...

EPFL2019

Bioengineering human bone marrow models to elucidate the triggers of the stem cell niche

Queralt Vallmajó Martín

The bone marrow (BM) microenvironment, or niche, significantly affects behaviors of its resident stem cell populations. Disruptions in the BM niche contribute to a number of severe clinical pathologies. Discovery of novel therapeutic strategies for BM-rela ...

EPFL2019

Quantitative relationships between SMAD dynamics and target gene activation kinetics in single live cells

Felix Naef, David Michael Suter, Torgil Elias Friman, Onur Tidin

The transduction of extracellular signals through signaling pathways that culminate in a transcriptional response is central to many biological processes. However, quantitative relationships between activities of signaling pathway components and transcript ...

2019

Targeted protein degradation through cytosolic delivery of monobody binders using bacterial toxins

Oliver Hantschel, Nadine Eliane Schmit, Katyayanee Neopane

Monobodies are small engineered binding proteins that, upon expression in cells, can inhibit signaling of cytosolic oncoproteins with outstanding selectivity. Efficacy may be further increased by inducing degradation of monobody targets through fusion to t ...

2019

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ ...

2019