Publications by Oliver Hantschel

Tuning SAS-6 architecture with monobodies impairs distinct steps of centriole assembly

Tatiana Favez, Pierre Gönczy, Virginie Hamel, Santiago Harald Andany, Georg Fantner, Oliver Hantschel, Georgios Hatzopoulos, Niccolo Banterle

Centrioles are evolutionarily conserved multi-protein organelles essential for forming cilia and centrosomes. Centriole biogenesis begins with self-assembly of SAS-6 proteins into 9-fold symmetrical ring polymers, which then stack into a cartwheel that sca ...

Nature Research2021

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

Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms

Florence Pojer, Matteo Dal Peraro, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Allan Joaquim Lamontanara, Tim Kükenshöner, Maria Josefina Marcaida Lopez, Daniel Pereira Duarte, Grégory La Sala

Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. Btk loss-of-function mutations cause human X-linked agammaglobulinemia (XLA). In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with ...

Nature Publishing Group2020

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

Florence Pojer, Oliver Hantschel, Tim Kükenshöner, Grégory La Sala, Kelvin Ka Ching Lau

The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere ...

Nature Research2020

Monobodies as enabling tools for structural and mechanistic biology

Oliver Hantschel

Monobodies, built with the scaffold of the fibronectin type III domain, are among the most well-established synthetic binding proteins. They promote crystallization of challenging molecular systems. They have strong tendency to bind to functional sites and ...

CURRENT BIOLOGY LTD2020

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

Jörg Hülsken, Anja Irmisch, Oliver Hantschel

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

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 phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis

Oliver Hantschel

2019

Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel

We present a rapid and high-throughput yeast and flow cytometry based method for predicting kinase inhibitor resistance mutations and determining kinase peptide substrate specificity. Despite the widespread success of targeted kinase inhibitors as cancer t ...

AMER CHEMICAL SOC2019

ATP Site Ligands Determine the Assembly State of the Abelson Kinase Regulatory Core via the Activation Loop Conformation

Oliver Hantschel, Allan Joaquim Lamontanara

2018

BioSITe: A Method for Direct Detection and Quantitation of Site-Specific Biotinylation

Oliver Hantschel, Sina Maren Reckel

2018

BCR-ABL1 compound mutants display differential and dose-dependent responses to ponatinib

Oliver Hantschel

2018

Development of Mirror-Image Monobodies for Targeted Cancer Therapies

Oliver Hantschel, Tim Kükenshöner, Timothy Matthias Reichart

WILEY2018

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

Romain Hamelin, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, 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

Kinase-templated abiotic reaction

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon

Protein kinases are quintessential regulators of cellular function. Numerous pathologies are intimately linked to the dysregulated activity of a particular protein kinase. Herein we report a technology based on a proximity-induced chemical transformation t ...

2017

Unpaired extracellular cysteine mutations of CSF3R mediate gain or loss of function

Oliver Hantschel, Tim Kükenshöner

Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g. T618I), functionally defective mutations in the extracellular domain of the granulocyte colony-stimulating factor receptor (CSF3R) have been reported only in seve ...

American Association for Cancer Research2017

Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies

Florence Pojer, Oliver Hantschel, Tim Kükenshöner, Nadine Eliane Schmit

The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant c ...

Elsevier2017

Bcr-Abl: one kinase, two isoforms, two diseases

Oliver Hantschel, Sina Maren Reckel

Impact Journals Llc2017

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

Single-molecule kinetic analysis of HP1-chromatin binding reveals a dynamic network of histone modification and DNA interactions

Vassily Hatzimanikatis, Louise Catherine Bryan, Georg Fantner, Pascal Damian Odermatt, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Beat Fierz, Sinan Kilic, Carolin Christine Lechner, Andreas Linus Bachmann, Daniel Robert Weilandt

Chromatin recruitment of effector proteins involved in gene regulation depends on multivalent interaction with histone post-translational modifications (PTMs) and structural features of the chromatin fiber. Due to the complex interactions involved, it is c ...

Oxford University Press (OUP)2017