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 Student

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.


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