Uni-Tübingen

P5: NO-cGMP mediated effects on platelet lipid metabolism and their role in governing thromboinflammation in stroke

Aims

To characterize the association between cGMP levels in platelets and the platelet lipidome driving thromboinflammation during stroke in murine stroke models and cerebral stroke patients. Further, we would like to validate the potential therapeutic impact of NO donors and cGMP analogs in regulating the platelet lipidome and, thereby, thrombotic disposition and thromboischaemic events.

Questions and Methods

cGMP and Platelet Lipid Metabolism

Boston Internship

Atochin Lab

In the Atochin lab in Boston, the doctoral researchers will be taught the

  1. middle cerebral artery occlusion (MCAO) stroke model,
  2. state of the art technologies to measure cerebral blood flow (CBF), and
  3. functional analysis of platelets in the murine stroke models.

Supported by the long standing expertise of the Atochin lab, CBF will be evaluated under basal conditions and following stroke in mice with perturbed cGMP signaling in platelets as well as in eNOS-/- bone marrow chimeras fed different diets.

Boston Co-mentor

Assist. Prof. Dmitriy Atochin, MD PhD

Link to boston researcher lab

Doctoral Students

Marcel Kremser

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.

Liubov Unger (associated PhD student)

Liubov Unger studied Pharmacy at the University of Kiel, Germany. Liubov comes from Moscow, Russia, and was awarded with a DAAD Prize for outstanding achievements in 2018 as a foreign student. She earned her approbation as a pharmacist in 2020. After her scientific internship at the Medical University of Warsaw in 2017, Liubov decided to pursue a scientific career. She has a strong interest for clinical research. Her goal is to investigate molecular mechanisms and signaling in cells. This fascination prompted her to join the laboratory of Prof. Robert Feil, where Liubov will focus on the role of cGMP in platelets also under supervision of Prof. Meinrad Gawaz.

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).


Key Publications

Vogel S, Bodenstein R, Chen Q, Feil S, Feil R, Rheinlaender J, Schäffer TE, Bohn E, Frick JS, Borst O, Munzer P, Walker B, Markel J, Csanyi G, Pagano PJ, Loughran P, Jessup ME, Watkins SC, Bullock GC, Sperry JL, Zuckerbraun BS, Billiar TR, Lotze MT, Gawaz M, Neal MD. Platelet-derived HMGB1 is a critical mediator of thrombosis. J Clin Invest. 2015;125:4638-54

Chatterjee M, Rath D, Schlotterbeck J, Rheinlaender J, Walker-Allgaier B, Alnaggar N, Zdanyte M, Müller I, Borst O, Geisler T, Schäffer TE, Lämmerhofer M, Gawaz M. Regulation of oxidized platelet lipidome: implications for coronary artery disease. Eur Heart J. 2017;38:1993-2005