Uni-Tübingen

P6: Does cGKI – through BK channels in the nuclear envelope – counteract activity-dependent acquired neuroprotection?

Aims

To define the role of cGKI-driven BK channels in the nuclear envelope of hippocampal neurons as regulators of nucleoplasmic [Ca2+] and transcriptional activity.

Questions and Methods

cGKI and Neuroprotection

Boston Internship

Roberts Lab

During the visit of the Roberts lab in Boston, the students will profit from its immense experience in examining nuclear cGKI function. This includes using

  1. wide-field imaging and statistical modeling to localize proteins within sub-cellular compartments, such as the nucleus and endomembrane system, and
  2. nuclear cGKI-regulated control of signaling using a genetically-encoded nuclear phospho-CREB biosensor probe and molecular imaging techniques.

Boston Co-mentor

Assoc. Prof. Jesse D. Roberts, MD

Link to boston researcher lab

Doctoral Student

Thomas Pham

Thomas Pham studied Pharmacy at the University of Tübingen and earned his approbation as a pharmacist in 2017. After his practical year in a pharmacy and pharmaceutical industry, he decided to discover the field of research, and therefore completed his Master's degree in Pharmaceutical Sciences and Technologies in the Lukowski Lab with a focus on the CNS. His interest in cellular signaling pathways inspired him to do his doctoral studies as part of the GRK 2381, where he investigates in the group of Peter Ruth the interaction of the BK channel and the cGMP signaling pathway in the nucleus to evaluate its impact on neuroprotection.


Key Publications

Föller M, Jaumann M, Dettling J, Saxena A, Pakladok T, Munoz C, Ruth P, Sopjani M, Seebohm G, Rüttiger L, Knipper M, Lang F. AMP-activated protein kinase in BK-channel regulation and protection against hearing loss following acoustic overstimulation. FASEB J. 2012;26:4243-53

Frankenreiter S, Bednarczyk P, Kniess A, Bork N, Straubinger J, Koprowski P, Wrzosek A, Mohr E, Logan A, Murphy MP, Gawaz M, Krieg T, Szewczyk A, Nikolaev VO, Ruth P, Lukowski R. cGMP-elevating compounds and ischemic conditioning provide cardioprotection against ischemia and reperfusion injury via cardiomyocyte-specific BK channels. Circulation. 2017;doi: 10.1161/CIRCULATIONAHA.117.028723