My lab investigates molecular mechanisms and translatable biomarkers that play a role in the dysfunction and rescue of striated muscles. Our lab aims to combine genetics, epigenetics and metabolism to garner a deeper understanding of muscle physiology and pharmacology.
An essential focus of the lab centers on "precision dosing" for glucocorticoid steroids in heart and muscle regulation. Glucocorticoids, such as dexamethasone, prednisone and deflazacort, are widely used as immunosuppressants. They have a pervasive, yet overlooked, impact on metabolic homeostasis and striated muscle function. We are investigating how repetitive versus pulsatile regimens of glucocorticoids remodel energy production and performance in several contexts of disease, including obesity, unhealthy aging and heart failure.
Moreover, we are leveraging the newly discovered pharmacological mechanisms to expand the concept of precision dosing for these drugs to "chrono-pharmacology." In this line of investigation, we are learning what circadian and molecular mechanisms govern steroid pharmacology and physiological response in striated muscles. Previously, we discovered that a change in intake frequency dramatically changes the effects of glucocorticoid steroids from pro-obesity to anti-obesity.
I have been a researcher for over 15 years and began my work with Cincinnati Children's in 2020. I am honored to be the recipient of several grants and awards, including:
Additional recognitions and awards include:
BS: Biotechnologies, University of Pavia, Italy, 2006.
MS: Experimental and Applied Biology, University of Pavia, Italy, 2008.
PhD: Biomedical Sciences, Catholic University of Leuven (KU Leuven), Belgium, 2013.
Muscle and heart physiology; pharmacology; epigenetics; metabolism
Molecular Cardiovascular Biology, Neuromuscular Development, Heart
Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model. The Journal of Clinical Investigation. 2024; 134.
Comprehensive Analyses of Muscle Function, Lean and Muscle Mass, and Myofiber Typing in Mice. Bio-protocol. 2023; 13:e4617.
Effects of Glucocorticoids in Murine Models of Duchenne and Limb-Girdle Muscular Dystrophy. Methods in molecular biology (Clifton, N.J.). 2023; 2587:467-478.
Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids. Molecular Metabolism. 2022; 62:101528.
Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin. The Journal of Experimental Medicine. 2022; 219.
Muscle mitochondrial remodeling by intermittent glucocorticoid drugs requires an intact circadian clock and muscle PGC1α. Science Advances. 2022; 8:eabm1189.
Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury. PLoS Genetics. 2017; 13:e1007070.
Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy. The Journal of Clinical Investigation. 2017; 127:2418-2432.
Mesodermal iPSC-derived progenitor cells functionally regenerate cardiac and skeletal muscle. The Journal of Clinical Investigation. 2015; 125:4463-4482.
Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic mice. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease. 2013; 2:e000284.
Mattia Quattrocelli, PhD4/1/2022
Mattia Quattrocelli, PhD2/18/2022