Person
Oliver Hantschel
This person is no longer with EPFL
Related publications (58)
Tuning SAS-6 architecture with monobodies impairs distinct steps of centriole assembly
Georg Fantner, Georgios Hatzopoulos, Tatiana Favez, Oliver Hantschel, Virginie Hamel, Niccolo Banterle, Santiago Harald Andany
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 RESEARCH2021Crizotinib 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)
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 ...
SPRINGER2021Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms
Matteo Dal Peraro, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Maria Josefina Marcaida Lopez, Oliver Hantschel, Allan Joaquim Lamontanara, Tim Kükenshöner, Grégory La Sala, Daniel Pereira Duarte
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 GROUP2020Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains
Florence Pojer, Kelvin Ka Ching Lau, Oliver Hantschel, Grégory La Sala
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 ...
2020Monobodies as enabling tools for structural and mechanistic biology
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 LTD2020γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia
Oliver Hantschel, 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 ...
2019Targeted 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 ...
2019Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity
Sandrine Madeleine Suzanne Georgeon, Oliver Hantschel, 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 SOC2019Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase
Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Charlotte Julie Caroline Gehin, Oliver Hantschel, Sina Maren Reckel, Tim Kükenshöner, Delphine Maude Tardivon, Barbara Gerig, Sara Raquel Pereira Pinho
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 Nature2017Selective 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 ...
2017