Uni-Tübingen

P4: The role of cGMP signaling for transdifferentiation of smooth muscle cells in atherosclerosis

Aims

To analyze how distinct components of the NO/cGMP signaling pathway affect the transdifferentiation potential of vascular smooth muscle cells (SMCs) in vascular disease.

Questions and Methods

cGMP and Atherosclerosis

Boston Internship

Huang Lab

In the Huang lab in Boston, the doctoral researchers will

  1. be trained in stroke models, e.g. the middle cerebral artery occlusion (MCAO) model, and
  2. learn about the vascular phenotypes of novel eNOS mutant mouse models (knockout and knock-in mice carrying phosphomimetic and unphosphorylatable mutations at S1176).

The process of transdifferentiation of SMCs in atherosclerosis and in the brain after stroke will be analyzed thereafter in Boston and in Tübingen.

Boston Co-mentor

Prof. Paul Huang, MD PhD

Link to boston researcher lab

Doctoral Students

Malte Roeßing

Malte Roeßing did his undergraduate studies in Biology at the Heinrich-Heine-University in Duesseldorf, where he was especially interested in protein biochemistry. Therefore, he did his bachelor’s thesis in the department of plant biochemistry, which dealt with the characterization of protein with an unknown function. In his master’s studies at Heinrich-Heine-University in Duesseldorf, he focused on molecular biomedicine. Due to his rising interest in the biochemical and pharmaceutical research field, he decided to do his master’s thesis at the Bayer AG in Wuppertal in the Biochemistry Department of the Institute Lead Discovery. The combination of the research on atherosclerosis with investigation of the important cGMP signaling system is a unique challenge for him as a young scientist. Thus, he decided to take up this challenge as a doctoral student of the GRK 2381 “cGMP: From Bedside to Bench” in the group of Dr. Susanne Feil. Here he is investigating the role of the cGMP signaling pathway in disease models of atherosclerosis.

Timo Kopp

Timo Kopp got his bachelor’s degree in Biology at the Johannes-Gutenberg-University in Mainz, where he was especially interested in molecular genetics. Accordingly, he did his bachelor’s thesis at the Department of Organismic and Molecular Evolutionary Biology, where he characterized a protein of unknown function. He then continued to earn his master’s degree in Biomedicine, where he focused on immunology. Due to his growing interest for this field of research, he decided to do his master’s thesis at the Department of Dermatology of the University Medical Centre, in which he investigated the influence of coagulation factors on the differentiation of macrophages from monocytes. After his M.Sc., Timo joined the group of Dr. Susanne Feil, to do his PhD. Here, his research focuses on pressure induced cGMP signalling in vascular smooth muscle cells.

Moritz Lehners (associated PhD student)

Moritz Lehners earned his Diploma in Biochemistry at the University of Tübingen with a focus on cellular signalling mechanisms and live cell imaging. His interest in the analysis of complex signalling networks prompted him to start a PhD at the laboratory of Prof. Dr. Robert Feil. Here he investigates the role of the cGMP signalling pathway in the plasticity of vascular smooth muscle cells and disease models of the cardiovascular system.


Key Publications

Feil S, Hofmann F, Feil R. SM22alpha modulates vascular smooth muscle cell phenotype during atherogenesis. Circ Res. 2004;94:863-5

Feil S, Fehrenbacher B, Lukowski R, Essmann F, Schulze-Osthoff K, Schaller M, Feil R. Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ Res. 2014a;115:662-7

Feil R, Lehners M, Stehle D, Feil S. Visualising and understanding cGMP signals in the cardiovascular system. Br J Pharmacol. 2021; epub 20 Apr 2021. doi: 10.1111/bph.15500. [pubmed] [Project 4] [Project 1]

Stehle D, Xu MZ, Schomber T, Hahn MG, Schweda F, Feil S, Kraehling JR, Eitner F, Patzak A, Sandner P, Feil R, Benardeau A. Novel sGC activators increase glomerular cGMP, induce vasodilation, and improve blood flow in the murine kidney. Br J Pharmacol. 2021; epub 7 Jun 2021. doi: 10.1111/bph.15586. [pubmed]  [Project 4] [Project 1]

Tchernychev B, Li H, Lee SK, Gao X, Ramanarasimhaiah R, Liu G, Hall KC, Bernier SG, Jones JE, Feil S, Feil R, Buys ES, Graul RM, Frenette PS, Masferrer JL. Olinciguat, a stimulator of soluble guanylyl cyclase, attenuates inflammation, vaso-occlusion and nephropathy in mouse models of sickle cell disease. Br J Pharmacol. 2021; epub 30 May 2021. doi: 10.1111/bph.15492 [pubmed]  [Project 4] [Project 1]