Molecular muscle physiology and pathophysiology
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:
- Elucidate the role of Ca2+ and free radicals in driving skeletal muscle remodeling.
- Identify and understand the mechanisms behind disease-induced muscle weakness.
- 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
Muscle dysfunction, comprising muscle weakness and altered metabolism, is a recurrent comorbidity in many diseases, incl. type 2 diabetes, peripheral artery disease, rheumatoid arthritis and cancer. This comorbidity can reduce both the ability to work and the quality of life for afflicted patients, since ordinary daily activities require extensive effort.
The common goal of the research in our laboratory is to elucidate the molecular mechanisms behind disease-induced muscle dysfunction and metabolic alterations. In particular, altered Ca2+ handling, oxidative stress and altered mitochondrial function appears as key factors in the intramuscular interplay that contributes to impaired muscle function. To reveal this, we apply a multidisciplinary approach involving in vivo and in vitro analysis in mice and humans, including force measurements, live imaging of Ca2+ and free radicals, metabolic profiles, mass spectrometry, and biochemical and molecular assays. We are also involved in developing novel therapeutic interventions to improve muscle function.
- The Swedish Research Council (VR)
- Jeansson foundation (page in Swedish)
- Karolinska Institutet
- Magnus Bergvall foundation (page in Swedish)
- Swedish Reumatism Association (page in Swedish)
Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis.
Steinz MM, Persson M, Aresh B, Olsson K, Cheng AJ, Ahlstrand E, et al
JCI Insight 2019 Mar;5():
Electrical Stimulation Prevents Preferential Skeletal Muscle Myosin Loss in Steroid-Denervation Rats.
Yamada T, Himori K, Tatebayashi D, Yamada R, Ashida Y, Imai T, et al
Front Physiol 2018 ;9():1111
Muscle Weakness in Rheumatoid Arthritis: The Role of Ca2+ and Free Radical Signaling.
Yamada T, Steinz MM, Kenne E, Lanner JT
EBioMedicine 2017 Sep;23():12-19
Neuromuscular electrical stimulation prevents skeletal muscle dysfunction in adjuvant-induced arthritis rat.
Himori K, Tatebayashi D, Kanzaki K, Wada M, Westerblad H, Lanner JT, et al
PLoS ONE 2017 ;12(6):e0179925
Docetaxel does not impair skeletal muscle force production in a murine model of cancer chemotherapy.
Chaillou T, McPeek A, Lanner JT
Physiol Rep 2017 Jun;5(11):
Superoxide dismutase/catalase mimetic EUK-134 prevents diaphragm muscle weakness in monocrotalin-induced pulmonary hypertension.
Himori K, Abe M, Tatebayashi D, Lee J, Westerblad H, Lanner JT, et al
PLoS ONE 2017 ;12(2):e0169146
Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.
Chaillou T, Lanner JT
FASEB J. 2016 12;30(12):3929-3941
Reactive oxygen/nitrogen species and contractile function in skeletal muscle during fatigue and recovery.
Cheng AJ, Yamada T, Rassier DE, Andersson DC, Westerblad H, Lanner JT
J. Physiol. (Lond.) 2016 09;594(18):5149-60
Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.
Place N, Ivarsson N, Venckunas T, Neyroud D, Brazaitis M, Cheng AJ, et al
Proc. Natl. Acad. Sci. U.S.A. 2015 Dec;112(50):15492-7
Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment.
Yamada T, Abe M, Lee J, Tatebayashi D, Himori K, Kanzaki K, et al
Skelet Muscle 2015 ;5():20
Nitrosative modifications of the Ca2+ release complex and actin underlie arthritis-induced muscle weakness.
Yamada T, Fedotovskaya O, Cheng AJ, Cornachione AS, Minozzo FC, Aulin C, et al
Ann. Rheum. Dis. 2015 Oct;74(10):1907-14
AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation.
Lanner JT, Georgiou DK, Dagnino-Acosta A, Ainbinder A, Cheng Q, Joshi AD, et al
Nat. Med. 2012 Jan;18(2):244-51
Ryanodine receptor physiology and its role in disease.
Adv. Exp. Med. Biol. 2012 ;740():217-34