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Cardioproteomics

Cardiovascular Disorders are one of the main causes of death in Western societies. Despite the establishment and availability of conventional heart failure therapies, (non)-invasive diagnostic tools and surgery methods, target-specific therapies and/ or diagnostic strategies are still lacking for a subset of cardiovascular disorders, including inflammatory cardiomyopathy and heart failure with preserved ejection fraction, of which the latest prevalence raises continuously.

The cardioproteomic group aims to determine protein signatures for patient, disease and therapy stratification and to find novel therapeutic targets, particularly of those cardiovascular disorders for which target-specific therapies are still not established and/or the pathogenesis is not fully understood.  The team focuses on sophisticated proteomics methodology for the exploration of the quantity and quality protein signatures, particularly in clinical samples. The proteomics methodology is closely affiliated with the CU Tissue Typing.  

Tissue assessment by imaging mass spectrometry enables personalized pathology based on the spatially determination of molecular signatures (e.g. proteins, peptides). In our group, we apply imaging mass spectrometry to investigate the development and progression, cellular-molecular inflammatory processes or mechanisms of regenerative tissue renewal in clinical tissue specimens.

Body fluid Profiling.  Robust and reproducible protein analyses techniques for the analysis of patient fluids specimens is a key requirement for the evolution of surgery methods, target-specific therapies and/ or diagnostic strategies for cardiovascular disorders. To overcome the limitations of traditional shotgun proteomics relating problems of missing data and reproducibility, we established hyper-reaction monitoring (HRM) mass spectrometry (MS). HRM-MS works via retention-time-normalized spectral libraries and enables unmatched proteome coverage with reproducible and precise protein quantification.

Research Focus

  • Stratification and classification of patient subgroups with cardiovascular disorders via protein profiling
  • Tissue assessment to classify cardiac disorders e.g. amyloidosis
  • Determination of novel specific therapy and/ or diagnostic targets

Methods

  • Analysis of protein quantity and quality by using liquid chromatography mass spectrometry
  • Tissue assessment via imaging mass spectrometry
  • Various protein preparations techniques in particular for clinical specimens

Selected Publications

  • Becker M, Maring JA, Oberwallner B, Kappler B, Klein O, Falk V, Stamm C. Processing of Human Cardiac Tissue toward Extracellular Matrix Self-Assembling Hydrogel for in Vitro and in Vivo Applications JoVE 2017
  • Kappler B, Anic P, Becker M, Bader A, Klose K, Klein O, Oberwallner B, Choi YH, Falk V, Stamm C. The cytoprotective capacity of processed human cardiac extracellular matrix. J Mater Sci Mater Med. 2016 Jul;27(7):120. doi: 10.1007/s10856-016-5730-5. Epub 2016 Jun 7.PMID: 27272902
  • Tschöpe C, Van Linthout S, Spillmann F, Klein O, Biewener S, Remppis A, Gutterman D, Linke WA, Pieske B, Hamdani N, Roser M. Cardiac contractility modulation signals improve exercise intolerance and maladaptive regulation of cardiac key proteins for systolic and diastolic function in HFpEF. Int J Cardiol. 2016 Jan 15;203:1061-6. doi: 10.1016/j.ijcard.2015.10.208. Epub 2015 Oct 27. No abstract available. PMID: 26638055
  • Kararigas G, Fliegner D, Forler S, Klein O, Schubert C, Gustafsson JA, Klose J, Regitz- Zagrosek V. Comparative Proteomic Analysis Reveals Sex and Estrogen Receptor β Effects in the Pressure Overloaded Heart. J Proteome Res. 2014;13:5829-36.
  • Klein O, Strohschein K, Nebrich G, Oetjen J, Trede D, Thiele H, Alexandrov T, Giavalisco P, Duda GN, von Roth P, Geissler S, Klose J, Winkler T. MALDI imaging mass spectrometry: Discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures. Proteomics. 2014;14:2249-60.
  • Klein O, Rohwer N, de Molina KF, Mergler S, Wessendorf P, Herrmann M, Klose J, Cramer T. Application of two-dimensional gel-based mass spectrometry to functionally dissect resistance to targeted cancer therapy. Proteomics Clin Appl. 2013;7:813-24.