Detail

Keywords

Alzheimer Disease; Blood Platelets; Embolism and Thrombosis; Hemostasis; Proteomics

Research interests

The main research aim of my working team is the proteomic exploration of the age-related vascular diseases such as thrombotic disorders and dementia. Vascular disease are rife in the industrialized nations, but little is known on the disease-related protein pattern at early stages and in the further course of the particular disease. We mainly use platelets for the diagnosis and functional exploration of vascular diseases. Moreover we take platelets also as a peripheral model for neurons to explore systemic changes in neurological diseases. Since platelets are an easily accessible tissue, they are very suitable for the development of diagnostic blood tests in routine diagnosis. The characterization of biomarkers, which identify the cause of various vascular diseases more directly, is an important component for a more targeted diagnosis and treatment in personalized medicine.

Research group members:

Felicia Hsu

Maria Zellner

Techniques, methods & infrastructure

Our central qualitative and quantitative proteomics tool for functional biomarker characterisation is fluorescence two dimensional gel electrophoresis (2D-DIGE). This electrophoresis technique is the cornerstone of the development of proteomics, but is used less and less nowadays because it cannot be automated. Our choice of this “top-down” proteomics technology is based on the aim of functional characterization of proteins along with their regulatory post-translational modifications. In summary, all of these protein variants are referred to as proteoforms. While the proteomics technology of "bottom-up" shotgun mass spectrometry, which is mainly used today, cannot detect this multitude of proteoforms simultaneously in a biological sample. In contrast, with 2D-DIGE proteomics technology, we can perform high-precision quantitative proteomics at the functional protein level in order to obtain data more helpful for reliable knowledge gain in "systems biology".

Technical application portfolio:

• clinical proteomics studies
• proteomics studies from in vitro and animal models
• two-dimensional gel electrophoresis, inclusively fluorescence 2D-DIGE
• mass spectrometry based protein identifications by LC-MS/MS
• exploration of posttranslational modifications, e.g. phosphoproteomics, glycoproteomics...
• 1D and 2D Western blot
• pathway analysis with various bioinformatics tools
• functional platelet studies (e.g. with flow cytometry, aggregometry,...)
• coagulation test, e.g. prothrombin time, partial thromboplastin time, enzymatic FXIIIA activity,..

Selected publications

1. Ercan, H. et al., 2021. Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability. Cancers, 13(9), p.2260. Available at: http://dx.doi.org/10.3390/cancers13092260.
2. Hell, L. et al., 2020. Altered platelet proteome in lupus anticoagulant (LA)-positive patients—protein disulfide isomerase and NETosis as new players in LA-related thrombosis. Experimental & Molecular Medicine, 52(1), pp.66–78. Available at: http://dx.doi.org/10.1038/s12276-019-0358-4.
3. Schmidt, G.J. et al., 2019. Comparative proteomics reveals unexpected quantitative phosphorylation differences linked to platelet activation state. Scientific Reports, 9(1). Available at: http://dx.doi.org/10.1038/s41598-019-55391-5.
4. Reumiller, C.M. et al., 2018. Gender-related increase of tropomyosin-1 abundance in platelets of Alzheimer’s disease and mild cognitive impairment patients. Journal of Proteomics, 178, pp.73–81. Available at: http://dx.doi.org/10.1016/j.jprot.2017.12.018.
5. Veitinger, M. et al., 2014. A platelet protein biochip rapidly detects an Alzheimer’s disease-specific phenotype. Acta Neuropathologica, 128(5), pp.665–677. Available at: http://dx.doi.org/10.1007/s00401-014-1341-8.