Biology subjects

Trautmann, M.

Publications and source records attributed to Trautmann, M..

3 recordsLinked to original sources

bioRxiv2025

Murder in cold blood? Forensic and bioarchaeological identification of the skeletal remains of Bela, Duke of Macso (c. 1245-1272)

In 1915, the remains of a male were discovered in a 13th-century monastery on Margaret Island, Budapest. Historical context suggested that the remains may belong to Duke Bela of Macso (c. 1245-1272), grandson of King Bela IV of Hungary (House of Arpad) and son of Duke Rostislav (Rurik dynasty). We applied a complex approach to identify the individual and reconstruct the circumstances of his death. Radiocarbon dating, when adjusted for freshwater reservoir effects linked to a high-protein diet, placed the burial in the mid-13th century. Skeletal features corresponded to a young adult male. Stable isotope and dental calculus analyses indicated a high-status diet rich in animal proteins and C3 cereals. Ancient DNA confirmed descent from King Bela III (Arpad dynasty) and Y-chromosomal affiliation with the Rurikid lineage. Forensic evidence revealed 26 perimortem injuries, suggesting a coordinated, premeditated assassination involving at least three assailants. The pattern of injuries indicates both planning and intense emotional involvement. Our findings provide the first genetic identification of a medieval royal, and resolve a century-old archaeological question, and illustrate the power of integrating multidisciplinary methods to confirm historical hypotheses and reconstruct violent deaths from the past with unprecedented detail. TeaserWith unprecedented details, this study shows the impact of integrating multidisciplinary methods to confirm historical hypotheses and reconstruct violent deaths from the past.

genetics↗

bioRxiv2024

Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma

The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. Since FUS::DDIT3 has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role of the cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS. Here we demonstrate that enhanced WEE1 pathway activity represents a hallmark of FUS::DDIT3-expressing cell lines as well as MLS tissue specimens and that WEE1 is required for MLS cellular survival in vitro and in vivo. Pharmacologic inhibition of WEE1 activity results in DNA damage accumulation and cell cycle progression forcing cells to undergo apoptotic cell death. In addition, our results uncover FUS::DDIT3-dependent WEE1 expression as an oncogenic survival mechanism to tolerate high proliferation and resulting replication stress in MLS. Fusion protein-driven G1/S cell cycle checkpoint deregulation via overactive Cyclin E/CDK2 complexes thereby contributes to enhanced WEE1 inhibitor sensitivity in MLS. These findings identify WEE1-mediated replication stress tolerance as molecular vulnerability in FUS::DDIT3-driven MLS tumorigenesis that could represent a novel target for therapeutic intervention.

cancer biology↗

bioRxiv2019

Focal adhesion kinase confers pro-migratory and anti apoptotic properties and is a potential therapeutic target in Ewing sarcoma

Oncogenesis of Ewing sarcoma (EwS), the second most common malignant bone tumor of childhood and adolescence, is dependent on the expression of chimeric EWSR1-ETS fusion oncogenes, most often EWSR1-FLI1 (E/F).\n\nE/F expression leads to dysregulation of focal adhesions (FAs) enhancing the migratory capacity of EwS cells. Here we show that, in EwS cell lines and tissue samples, focal adhesion kinase (FAK) is expressed and phosphorylated at Y397 in an E/F-dependent way involving Ezrin. Employing different EwS cell as in vitro models, we found that key malignant properties of E/F are mediated via substrate-independent autophosphorylation of FAK on Y397. This phosphorylation results in enhanced FA formation, Rho-dependent cell migration, and impaired caspase-3-mediated apoptosis in vitro. Conversely, treatment with the FAK inhibitor Y15 enhanced caspase-mediated apoptosis and EwS cell migration, independent from the respective EWSR1-ETS fusion type, mimicking an anoikis-like phenotype. Our findings were confirmed in vivo using an avian chorioallantoic membrane (CAM) model. Our results provide a first rationale for the therapeutic use of FAK inhibitors to impair metastatic dissemination of EwS.

cancer biology↗