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Concept

Chromosome de Philadelphie

Publications associées (29)

Spatially multiplexed single-molecule translocations through a nanopore at controlled speeds

Aleksandra Radenovic, Georg Fantner, Sanjin Marion, Vytautas Navikas, Samuel Mendes Leitão, Barney Frederick Drake, Simon Finn Mayer, Helena Miljkovic, Gordanna Pistoletti Blanchet

In current nanopore-based label-free single-molecule sensing technologies, stochastic processes influence the selection of translocating molecule, translocation rate and translocation velocity. As a result, single-molecule translocations are challenging to ...

2023

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Natalya Katanayeva, Daniele Tavernari, Ruxandra-Andreea Lambuta, Juan Diaz Miyar

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

NATURE PORTFOLIO2023

Whole genome doubling promotes tumorigenesis through loss of chromatin segregation and compartment repositioning

Ruxandra-Andreea Lambuta

Whole genome doubling (WGD) events are drivers of genetic innovation across vertebrate evolution. While generally detrimental to mammalian organisms, WGDs are crucial in the development of various plants and fungi, as well as for the terminal differentiati ...

EPFL2023

Preomic profile of BxPC-3 cells after treatment with BRC4

Andrea Cavalli

BRCA2 and RAD51 are two proteins that play a central role in homologous recombination (HR) and DNA double strand break (DSB) repair. BRCA2 assists RAD51 fibrillation and defibrillation through binding with its eight BRC repeats, with BRC4 being one of the ...

ELSEVIER2023

TFIIH moonlighting at telomeres

Joachim Lingner, Galina Glousker

Although telomeres are essential for chromosome stability, they represent fragile structures in our genome. Telomere shortening occurs during aging in cells lacking telomerase due to the end replication problem. In addition, recent work uncovered that the ...

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT2022

Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1(T315I) and BCR-ABL1(T315I-E255K)

Oliver Hantschel

Resistance remains the major clinical challenge for the therapy of Philadelphia chromosome-positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common "gatekeeper" mutation T315I ...

SPRINGER2021

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Elisa Oricchio, Daniele Tavernari, Natalya Katanayeva, Stephanie Jocelyne Sungalee, Ruxandra-Andreea Lambuta

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is a ...

2021

Passive and active ion permeation through lipid bilayers investigated by second harmonic water imaging

Maksim Eremchev

Lipid membranes are complex and dynamic systems which are known to mediate signaling processes between cells and their environment. To do this multiple ion channels and pumps are involved in controlling the in- and out-flux of various ions (K+, Na+, Mg2+, ...

EPFL2021

Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau

Hilal Lashuel, Anass Chiki, Galina Limorenko, Nadine Aït Bouziad

The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau's norma ...

2020

Wafer-level fabrication of individual solid-state nanopores for sensing single DNAs

Miao Zhang

For biomolecule sensing purposes a solid-state nanopore platform based on silicon has certain advantages as compared to nanopores on other substrates such as graphene, silicon nitride, silicon oxide etc Capitalizing on the developed CMOS technology, nanopo ...

2020

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

Oliver Hantschel, Jörg Hülsken, Anja Irmisch

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

Novel therapeutic strategies targeting the B-cell receptor signaling and antigen presentation pathways in non-Hodgkin lymphoma

Elena Battistello

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

Cytosolic delivery and characterization of monobodies interfering with SH2 domain-phosphotyrosine interactions

Nadine Eliane Schmit

Targeted cancer therapy is a very promising concept; however, small molecule inhibitors only exist for a limited number of oncoproteins and resistance development limits their clinical use. Different engineered non-antibody scaffolds are being explored to ...

EPFL2018

Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

Romain Hamelin, Sandrine Madeleine Suzanne Georgeon, Oliver Hantschel, Sina Maren Reckel

The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphobl ...

Nature Publishing Group2017

Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

Oliver Hantschel, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel, Charlotte Julie Caroline Gehin, Tim Kükenshöner, Delphine Maude Tardivon, Barbara Gerig

The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study ...

Springer Nature2017

Allosteric kinase inhibitors

Oliver Hantschel

Background. Inhibition of the kinase activity of the BCR-ABL1 oncoprotein by an allosteric mechanism of action facilitates alternative treatment options for chronic myeloid leukemia (CML) patients who cannot be adequately treated with conventional catalyti ...

Springer Nature2017

Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases

Oliver Hantschel

Leukemias expressing constitutively activated mutants of ABL1 tyrosine kinase (BCR-ABL1, TEL-ABL1, NUP214-ABL1) usually contain at least 1 normal ABL1 allele. Because oncogenic and normal ABL1 kinases may exert opposite effects on cell behavior, we examine ...

American Society of Hematology2016

Allosteric regulation and targeting of Abl SH2-kinase interface and other cytoplasmic tyrosine kinases

Allan Joaquim Lamontanara

Due to their central role in normal cellular physiology, the activity of protein kinases is tightly regulated and their aberrant activation can lead to cancer. Chronic myelogenous leukemia (CML) is a blood cancer characterized by unregulated growth of myel ...

EPFL2016

Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface

Oliver Hantschel, Allan Joaquim Lamontanara, Barbara Gerig

Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase do ...

American Society for Biochemistry and Molecular Biology2016

Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis

Bruno Lemaitre, Toshiyuki Harumoto

Some symbiotic bacteria are capable of interfering with host reproduction in selfish ways. How such bacteria can manipulate host's sex-related mechanisms is of fundamental interest encompassing cell, developmental and evolutionary biology. Here, we uncover ...

Nature Publishing Group2016