Calcium signaling and molecular muscle physiology
We study molecular mechanisms behind muscle remodeling and contractile dysfunction. We are also involved in developing novel therapeutic interventions to treat skeletal muscle weakness.
The lab has three overall goals: I. Elucidate the role of Ca2+ and free radicals in driving skeletal muscle remodeling. II. Identify and understand the mechanisms behind disease-induced muscle weakness. III. Develop novel therapeutic interventions to treat skeletal muscle weakness.
We use a wide variety of methods to study these processes, ranging from single proteins via intact muscles to in vivo experiments and translational in humans.
Research in our laboratory
Calcium (Ca2+) is essential for muscle contraction and plays a central role in our research. In fact, every step you take is dependent on Ca2+ release from the major intracellular Ca2+ release channel, the ryanodine receptor (RyR). With this in mind it is easy to envisage that disturbed Ca2+ handling results in both skeletal muscle dysfunction.
Severe illnesses, such as rheumatoid arthritis, diabetes, renal failure and cancer, are commonly associated with secondary muscle complications, such as weakness. These muscle complications may even be the dominating symptom by reducing the quality of life for afflicted patients, since ordinary daily activities require extensive effort, and in the worst case cause premature mortality. Reduced muscle strength has always been more or less synonymous with decreased muscle mass. However, our research has started to re-draw the map showing that muscle weakness is not only a result of atrophic muscles. Instead, one of the important factors is impaired contractility (i.e. force per cross-sectional area is reduced) caused by an imbalance of ROS signaling in muscle. Thus, we are particularly interested in how intracellular Ca2+ signaling and free radicals (reactive oxygen/nitrogen species) control muscle contraction. With genetic manipulation, pharmacological tools and/or exercise interventions, we try to manipulate intracellular Ca2+ and free radicals in order to improve contractility and muscle function both in the short- and long-term.
|Thomas Chaillou||Post doc|
|Arthur Cheng||Post doc|
|Arturo Uribe Gonzalez||R&D trainee|
|Niklas Ivarsson||PhD student|
|Johanna Lanner||Research group leader|
|Gianluigi Pironti||Post doc|
|Maarten Steinz||PhD student|
- The Swedish Research Council
- Jeansson foundation (page in Swedish)
- Karolinska Institutet
- Magnus Bergvall foundation (page in Swedish)
- Swedish Reumatism Association
Can't live with or without it: calcium and its role in Duchenne muscular dystrophy-induced muscle weakness. Focus on "SERCA1 overexpression minimizes skeletal muscle damage in dystrophic mouse models".
Am. J. Physiol., Cell Physiol. 2015 May;308(9):C697-8
Ca2+ permeation and/or binding to CaV1.1 fine-tunes skeletal muscle Ca2+ signaling to sustain muscle function.
Lee CS, Dagnino-Acosta A, Yarotskyy V, Hanna A, Lyfenko A, Knoblauch M, Georgiou DK, Poche RA, Swank MW, Long C, Ismailov II, Lanner JT, et al.
Skeletal Muscle. 2015 Jan 29;5:4.
Antioxidant treatments do not improve force recovery after fatiguing stimulation of mouse skeletal muscle fibres.
J. Physiol. (Lond.) 2014 Nov;():
Ligands for FKBP12 increase Ca2+ influx and protein synthesis to improve skeletal muscle function.
J. Biol. Chem. 2014 Sep;289(37):25556-70
Nitrosative modifications of the Ca2+ release complex and actin underlie arthritis-induced muscle weakness.
Ann. Rheum. Dis. 2015 Oct;74(10):1907-14
Ryanodine receptor physiology and its role in disease.
Adv. Exp. Med. Biol. 2012 ;740():217-34
AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation.
Nat. Med. 2012 Jan;18(2):244-51
Ryanodine receptors: structure, expression, molecular details, and function in calcium release.
Cold Spring Harb Perspect Biol 2010 Nov;2(11):a003996