(PhD – Technical University, Berlin)
HONORS & AWARDS
- NIH MERIT Award: 2010
- Fellow of the Biophysical Society: 1999
- NIH MERIT Award: 1990
- Established Investigator of American Heart Association: 1972
The laboratory’s research focuses on defining the molecular basis of Ca2+ release channel/ryanodine receptor (RyR1) function in skeletal muscle. RyR1s are 2,200 kDa ion channels that release Ca2+ ions in response to an action potential from the sarcoplasmic reticulum, an intracellular Ca2+-storing compartment in skeletal muscle. In our studies, we use mutagenesis, Ca2+ imaging and single channel measurements to determine the molecular mechanisms underlying RyR1 function. As our studies progress we expect to gain new insights in the complex mechanisms of RyR1 channel ion conductance and selectivity, and gating by its multiple ligands, and how these processes are altered by mutations in RyR1 linked to muscle diseases such as central core disease and malignant hyperthermia.
- Chirasani VR, Xu L, Addis HG, Daniel Pasek DA , Dokholyan NV, Meissner G, Yamaguchi N. A central core disease mutation in the Ca2+ binding site of skeletal muscle ryanodine receptor impairs single-channel regulation. Am J Physiol – Cell Physiol 317, C358-C365, 2019.
- Xu L, Chirasani VR, Carter JS, Pasek DA, Dokholyan NV, Yamaguchi N, Meissner G. Ca2+-mediated activation of the skeletal-muscle ryanodine receptor ion channel. J Biol Chem 293, 19501-19509, 2018.
- Xu L, Mowrey DD, Chirasani VR, Wang Y, Pasek DA, Dokholyan NV, Meissner G: G4941K substitution in the pore-lining S6 helix of the skeletal muscle ryanodine receptor increases RyR1 sensitivity to cytosolic and luminal Ca2+. J Biol Chem 293, 2015-2028, 2018.
- Mowrey DD, Xu L, Mei Y, Pasek, DA, Meissner G, Dokholyan NV: Ion-pulling simulations provide insights into the mechanisms of channel opening of the skeletal muscle ryanodine receptor. J Biol Chem 292, 12947-12958, 2017.
- Meissner, G. The structural basis of ryanodine receptor ion channel function. J Gen Physiol. 149:1065-1089, 2017.
- Xu L, Gomez AC, Pasek DA, Meissner G, Yamaguchi N: Two EF-hand motifs in ryanodine receptor calcium release channels contribute to isoform-specific regulation by calmodulin. Cell Calcium 66, 62-70, 2017.
- Huang TQ, Willis MS, Meissner G: IL-6/STAT3 signaling in mice with dysfunctional type-2 ryanodine receptor. JAK-STAT 4, e1158379, 2016.
- . Mei Y, Xu L, Mowrey DD, Mendez Giraldez R, Wang Y, Pasek DA, Dokholyan NV, Meissner G: Channel gating dependence on pore lining helix glycine residues in skeletal muscle ryanodine receptor. J Biol Chem 290, 17535-17545, 2015.
- Xie L, Pi X, Townley-Tilson WHD, Li N, Wehrens XHT, Entman ML, Taffet GE, Mishra A, Peng J, Schisler JC, Meissner G, Patterson C: PHD2/3-dependent hydroxylation tunes cardiac response to β-adrenergic stress via phospholamban. J Clin Invest 125, 2759-2771, 2015.