Start-up Funding: Mechanosensitive cGMP signalling in vascular smooth muscle cells (January 2025 to December 2025)

Aims

To elucidate the mechanosensitive cGMP signalling complex in vascular smooth muscle cells.

Questions and Methods

cGMP and mechanical force

• Which proteins are involved in sensing and transferring mechanical stimuli, influencing cGMP generation in vascular smooth muscle cells (mechano-cGMP)?
• Does mechano-cGMP contribute to vascular auto-regulation under physiological conditions?
• Do vascular diseases (e.g. atherosclerosis) have an impact on the mechanical environment of vascular smooth muscle cells and alter mechano-cGMP?
• Do drugs that are used in humans to treat vascular diseases (e.g. Riociguat for pulmonary hypertension) alter mechano-cGMP and does this give hints about the mechanism?
• Imaging of cGMP, via the biosensor cGi500, is a method to investigate the influence of mechanical forces on cGMP signalling in vascular smooth muscle cells, segments of intact vessels and living animals.
• Atomic force microscopy measures cellular and tissue stiffness and allows to investigate potential correlations to mechano-cGMP (collaboration with P3 and Dr. Aylin Balmes).

Career path

Timo studied biology and biomedicine at the University of Mainz, with a focus on immunology. In the course of his studies, he developed an interest in researching the molecular basis of (vascular) disease development, which led him to join the GRK 2381 and do a PhD in the Feil lab. During his PhD, he aimed to decipher the influence of mechanical forces on the cGMP signalling pathway (mechano-cGMP) in vascular smooth muscle cells. For this purpose, he established ex vivo real-time cGMP imaging in pressurized blood vessels. While doing an internship in the lab of Assoc. Prof. Dmitriy Atochin, PhD, MD, in Boston, he additionally investigated the influence of near-infrared lasers on cGMP signalling. As a postdoc, Timo will continue his work on the topic of mechano-cGMP, with the aim to elucidate the signalling complex involved.

Publications

Katagiri W, Yokomizo S, Ishizuka T, Yamashita K, Kopp T, Roessing M, Sato A, Iwasaki T, Sato H, Fukuda T, Monaco H, Manganiello S, Nomura S, Ng MR, Feil S, Ogawa E, Fukumura D, Atochin DN, Choi HS, Kashiwagi S. Dual near-infrared II laser modulates the cellular redox state of T cells and augments the efficacy of cancer immunotherapy. FASEB J 2022, 36:e22521.

Yokomizo S, Roessing M, Morita A, Kopp T, Ogawa E, Katagiri W, Feil S, Huang PL, Atochin DN, Kashiwagi S. Near-infrared II photobiomodulation augments nitric oxide bioavailability via phosphorylation of endothelial nitric oxide synthase. FASEB J 2022, 36:e22490.

Yokomizo S, Kopp T, Roessing M, Morita A, Lee S, Cho S, Ogawa E, Komai E, Inoue K, Fukushi M, Feil S, Kim H, Bragin DE, Gerashchenko D, Huang PL, Kashiwagi S, Atochin DN. Near-infrared II photobiomodulation preconditioning ameliorates stroke injury via phosphorylation of eNOS., Stroke. 2024; 55:1641-1649. doi: 10.1161/STROKEAHA.123.045358.

Sigle M, Rohlfing AK, Cruz Santos M, Kopp T, Krutzke K, Gidlund V, Kollotzek F, Marzi J, von Ungern-Sternberg S, Poso A, Heikenwälder M, Schenke-Layland K, Seizer P, Möllmann J, Marx N, Feil R, Feil S, Lukowski R, Borst O, Schäffer TE, Müller KAL, Gawaz MP, Heinzmann D. Targeting Cyclophilin A in the Cardiac Microenvironment Preserves Heart Function and Structure in Failing Hearts., Circ Res. 2024; 135:758-773. doi: 10.1161/CIRCRESAHA.124.324812.

Budbazar E*, Balmes A*, Elliott D, Tintin LP, Kopp T, Feil S, Feil R, Schäffer TE, Seta F. 2025. Pharmacological activation of NO-sensitive guanylyl cyclase ameliorates obesity-induced arterial stiffness. Vascul. Pharmacol. 2025; 159, 107503. doi: 10.1016/j.vph.2025.107503. *Contributed equally.