Ongoing Projects

Impact of a newly identified MET receptor tyrosine kinase phosphorylation site on MET-mediated physiologic and oncogenic signaling

MET, the tyrosine kinase receptor for hepatocyte growth factor, activates a wide range of different cellular signaling pathways, including those involved in proliferation, motility, migration, and invasion. Apart from promoting biological features that are associated with tumor growth and progression, accumulating data suggest that MET signaling may protect tumor cells from DNA damage, conceivably by signaling through the DNA damage response. We have identified a previously unreported phosphorylation site on MET, which is present in the context of a phosphorylation motif recognized by DNA damage master kinases. The goal of this Swiss National Science Foundation-funded project is to dissect the nature, function, and regulation of the novel MET phosphorylation site in the context of its physiological as well as oncogenic signaling by employing distinct in vitro and in vivo models.

SPRR2A in invasiveness and therapeutic resistance in head and neck squamous cell carcinoma

Radiotherapy resistance of head and neck squamous cell carcinoma (HNSCC) is one of the main factors contributing to treatment failure but the underlying molecular mechanisms are largely unknown. Genomic profiling of patient-matched HNSCC cell lines derived from primary and secondary diseases indicated the small proline-rich protein 2A (SPRR2A) as the most differentially regulated gene in both metastatic and recurrent cells as compared to their matched primary counterparts. In this study, we aim to elucidate the role of SPRR2A in pathogenesis and radiotherapy resistance of HNSCC.

Immune signatures to predict chemoradiation-induced toxicities in head and neck cancer patients

Head and neck squamous cell carcinoma (HNSCC) patients are predominantly treated by organ-sparing approaches consisting of chemoradiation. While such approaches have improved the rates of locoregional disease control, this has been associated with substantial early and late toxicities that have a detrimental effect on the quality of life. We are employing a unique cross-field discovery approach to correlate toxicity after chemoradiation with targeted immune blood-based biomarkers from high-dimensional single-cell data. This project is an Innosuisse-funded collaboration with Scailyte AG, a Swiss company developing artificial intelligence technologies for biomedical research, pharmaceutical discovery, and diagnostics.

Identification of synthetic interactions in CHK2-deficient cancers

Checkpoint kinase 2 (CHK2) is a DNA damage response-related protein that is essential for cell cycle regulation. CHK2 abnormal activity can contribute to the development of various cancer types and CHK2 gene mutations are associated with breast cancer resistance to anthracycline-based chemotherapy. In this project, we are exploiting the concept of synthetic lethality to identify selective treatments for CHK2-deficient tumors by performing kinase-targeting pharmacological and kinome-wide CRISPR/Cas9 knock-out screens.