Imaging MS innovative technology combines the comprehensive mass spectrometric technique with a conventional histological evaluation. It allows analysis of biomolecules directly on a single tissue section, preserving their spatial distribution and generating a molecular intensity map displaying the spatial relative molecule abundance. These technologies can be used in the assessment of tissue based on molecular signatures, single biomolecules and allows the performance of high-throughput analyses to aid the evolution of diagnostics tools or therapy stratification . Three groups in the MSTARS consortium use this powerful tool to analyze molecular changes directly in tissue sections aiming for a classification of the biomolecular to predict therapy responses.
Oliver Klein and his team has long-standing expertise in the field of MS based Imaging, using this advanced method for the histopathological determination of molecular (proteins, peptides, metabolites, gylcans), cellular or structural changes directly in tissue sections. This method allows the characterization of spatial and temporal molecular alterations, as a consequence of a diseased state or therapy-driven regenerative processes, and supports along that line the development of molecular classifiers for therapy stratification or diagnosis/prognosis tools. The lab is equipped with a variety of mass spectrometers, e.g. MALDI TOF Imaging MS, A, ESI-QTOF MS, nano HPLC, sprayer devices and a whole slide imaging scanner.
In the MSTARS consortium the lab of Oliver Klein uses imaging MS to address molecular alterations in tumor tissue sections label-free, supporting the development of predictors for diagnosis and treatments. They analyze untreated and treated patient-derived HNSCC models and patient tissue samples for molecular alterations of the tumor tissue, shedding light on changes in the microenvironment due to therapeutic interventions. In combination with machine learning approaches, these analyses result in classifiers that define treatment success or failure. In the long run, the analyses will be extended to other disease entities, such as ovarian cancer, neuroblastoma, prostate cancer, or myocarditis.
Benjamin Florian Hempel, Oliver Klein, Zhyiang Wu, Grit Nebrich, Sylwia Handzig
The research of Marie-Laure Yaspo’s lab focuses on cancer genomics and the systems biology of cancer. They established a powerful integrative next generation sequencing (NGS) analysis pipeline exploiting genome and transcriptome information to identify pathway components and biomarkers associated with malignancy and to explore gene regulation networks operating in specific cancer entities. In addition, they use RNAseq for tumor profiling, enabling the detection of consequences of somatic events at gene expression levels. A second branch of the Yaspo lab is tumor immunology. There they focus on the identification of the stroma niche and immune cell infiltrates in various tumors and use NGS-based methods to characterize the human immune cell repertoire and immune status in health and disease.
As part of the MSTARS consortium the Yaspo lab conducts CyTOF-based imaging MS to characterize spatially target molecules in tissue sections on the single cell level. The combined analysis of molecular alterations and the single cell distribution enables a deeper insight into the disease progress and therapy response. Hence, this approach is used to address HNSCC patients with a primary or secondary resistance to targeted therapy. These analyses might uncover correlations between one or the other type of resistance and molecular alterations or changes in the cellular composition. In addition, a focus is set on the composition of the tumor infiltrating cells, which provide information on therapy resistance and can be translated to other disease entities.
Dietrich Volmer and his lab are enthusiasts of biological MS, focusing on clinical MS, metabolomics, high-resolution MS of complex natural organic matter, and instrument development. In exemplary projects they e.g. deal with the advancement of MS techniques to analyze the Vitamin D metabolome or to shed light on complex lignin structures via novel lignomics technologies. In order to conduct their analyses, the Volmer lab is equipped with a variety of mass spectrometers for e.g. structural MS analysis, MS imaging and quantitative MS.
In the context of MSTARS, the Volmer lab analyses the reaction of the tumor microenvironment upon therapeutic intervention. The research focus is the impact of the microenvironment on the distribution, activation and effectiveness of anti-tumor active substances and their main metabolites. The metabolites differ in their physicochemical characteristics from the original substances, thus, a distinct distribution inside the tumor is expected. The Volmer team applies MS Imaging, with devices that enable ultrahigh spatial and mass resolution, to analyze anticancer drug metabolites and other species such as lipids, aiming for the identification of diagnostic and prognostic imaging MS-derived biomarkers for tissue classification and predictions of therapy responses in HNSCC patients. In the long run, the established workflow will be adapted to other disease entities.