Uni-Tübingen

P5: Role of hemin-dependent signaling and ferroptosis in platelets: does cGMP play a role?

Aims

To dissect the interplay of cGMP/cGKI signals with hemin-induced platelet activation driving severe clinical conditions such as hemolysis, thrombosis and thrombocytopenia.

Questions and Methods

cGMP and Platelets

Chicago Internship

Xiaoping Du Lab

In the Xiaoping Du Lab in Chicago, the doctoral researchers will be further trained in molecular biology methodology with a focus on studying nitric oxide-cGMP-dependent signaling pathway in regulating platelet function, as well as the role of cGMP and platelet ferroptosis.

Chicago Co-mentor

Xiaoping Du, MD, PhD

link to Chicago researcher lab

Doctoral Students

Marcel Kremser (graduated in November 2023)

Marcel Kremser earned his B.Sc. in Molecular Biology at the University in Bielefeld with a focus on cell biology. After earning his M.Sc. in Medical Biology in Essen, Marcel began his doctoral studies in the laboratory of Meinrad Gawaz. Here, his research focusses on the role of cGMP signaling in platelets and further deepens our understanding of cardiovascular diseases.

Valerie Dicenta

Valerie Dicenta studied Biotechnology at the University of applied Science in Esslingen. In her bachelor’s thesis she established a capillary electrophoresis mass spectrometry method for the characterization of the primary structure of therapeutic monoclonal antibodies at the Sanofi-Aventis Deutschland GmbH in Frankfurt. She completed her Master’s degree in Industrial Biotechnology at the University of Ulm and Biberach. In her thesis she focused on the inhibition of virulence associated proteases from prominent bacterial pathogens as a possible alternative to antibiotics. Valerie joined the group of Prof. Meinrad Gawaz working on the role of platelets and their signaling to understand cardiovascular diseases and to find possible ways for treatments.

Daniel Pinto Quintero (associated PhD student)

Daniel Pinto Quintero obtained his Bachelor's degree in Human biology from Phillips University in Marburg where he developed a special interest in tumor biology. During his Bachelor thesis, he investigated the aberrant expression pattern of GAPDH on salivary gland tumors.Following his interest in biomedical research, he then continued his Master studies in Human biology at the University of Marburg. For his Master thesis, Daniel was working in a radiation oncology laboratory investigating a putative detrimental role of serum amyloid A limiting the success of radiotherapy in head and neck cancer. Daniel currently focuses on the investigation of the relationship between shear stress and cGMP signaling in platelets. In the future, this might lead to improved treatment options for patients with blood clotting disorders (thrombosis).

Anne-Katrin Rohlfing (associated Postdoc)

Dr. Anne-Katrin Rohlfing studied biology at the Ernst-Moritz-Arndt-University Greifswald and received her Diplom in Biology in 2003. For her dissertation, she studied cell cycle regulation in the animal physiology group of Prof. Dr. J.-P. Hildebrand at the Zoological Institute and Museum at the Ernst-Moritz-Arndt-University Greifswald and received a Dr. rer. nat in 2007. Afterwards, she worked from 2007 as PostDoc in the laboratory of Prof. T. Lamitina at the Perelmann School of Medicine, Department of Physiology of the University of Pennsylvania researching the osmotic stress response in C. elegans. In 2009 she joined the physiology group of Prof. Dr. Walz at the University of Potsdam as PostDoc also working on osmotic stress resistance.  In 2014 Dr. Rohlfing gained DFG Eigene Stelle grant (DFG Project RO4279/3-1) and worked until 2018 as junior group leader associated with the animal physiology group of Prof. Dr. S. Seyfried at the University of Potsdam. In 2018 Dr. Rohlfing joined the research group of Prof. Dr. M. Gawaz, Internal Medicine III - Cardiology and Angiology at the University Hospital Tübingen as group leader researching platelet physiology and pathology in cardiac disease conditions.


Key Publications

Fink A, Rohlfing A-K, Dicenta V, Schaale D, Kremser M, …, Gawaz MP. 2023. The subtilisin-like protease furin regulates hemin-dependent ectodomain shedding of glycoprotein VI (GPVI). Thromb Haemost 2023, 123(7):679-691. doi: 10.1055/s-0043-1768057

Bayrak A, Mohr F, Kolb K, Szpakowska M, Shevchenko E, Dicenta V, Rohlfing AK, Kudolo M, Pantsar T, Gunther M, Kaczor AA, Poso A, Chevigne A, Pillaiyar T, Gawaz M, Laufer SA. Discovery and development of first-in-class ACKR3/CXCR7 superagonists for platelet degranulation modulation. J Med Chem 2022, 65:13365-84. doi:10.1021/acs.jmedchem.2c01198

Nestele JA, Rohlfing AK, Dicenta V, Bild A, Eissler D, Emschermann F, Kremser M, Krutzke K, Schaffer TE, Borst O, Levi M, Korin N, Gawaz MP. Characterization of GPVI- or GPVI-CD39-coated nanoparticles and their impact on in vitro thrombus formation. Int J Mol Sci 2021, 23: doi:10.3390/ijms23010011

Petersen-Uribe A, Kremser M, Rohlfing AK, Castor T, Kolb K, Dicenta V, Emschermann F, Li B, Borst O, Rath D, Muller KAL, Gawaz MP. Platelet-derived PCSK9 is associated with LDL metabolism and modulates atherothrombotic mechanisms in coronary artery disease. Int J Mol Sci 2021, 22: doi:10.3390/ijms222011179

Rohlfing AK, Kolb K, Sigle M, Ziegler M, Bild A, Munzer P, Sudmann J, Dicenta V, Harm T, Manke MC, Geue S, Kremser M, Chatterjee M, Liang C, …, Lammerhofer M, Autenrieth SE, Schaffer TE, Laufer S, Szklanna P, Maguire P, …, Rath D, Gawaz M. ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury. Nat Commun 2022, 13:1823. doi:10.1038/s41467-022-29341-1