MD at University of Pavia, Specialization in Cardiology and in Sport Medicine,

Visiting scientist at Dept of Pharmacology, University of Lund (sweden) 1980-1984,

Associate professor in Physiology at the University of Pavia since 1984, Full Professor of Physiology at the University of Pavia (1991-1999) and then Padova (2000-to present), teaching physiology to medical students and movement science students.

Director of the School of Sport Medicine In Pavia (1997-99) and in Padova (2009-2012).

Director of the undergraduate course of Human Movement Science in Padova since 2009 to present.

Authors of 168 papers indexed in Pubmed with a total of 6333 citations and h index 38, according to Scopus (autumn 2013)

muscle fibre diversity and specialization
muscle fibre diversity and specialization
muscle fibre plasticity in relation to activity and disuse
muscle fibre plasticity in relation to activity and disuse
calcium signaling for regulation of muscle fibre contraction
calcium signaling for regulation of muscle fibre contraction

1) muscle fibre diversity and specialization: Mammalian skeletal muscles are heterogeneous in nature. They comprise different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Present research activity covers further advanced investigation on myosin isoform diversity and new attempts to achieve a global view of muscle fibre specialization based on transcriptomic and proteomic approach. In the figures below a philogenetic tree of myosin heavy chain isoforms and a compilation of diagrams showing the impact of myosin heavy chain isoforms on several functional parameters.

2) muscle fibre plasticity in relation to activity and disuse: Mammalian skeletal muscles are composed of a variety of highly specialized fibers whose selective recruitment allows muscles to fulfill their diverse functional tasks. In addition, skeletal muscle fibers can change their structural and functional properties to perform new tasks or respond to new conditions. The adaptive changes of muscle fibers can occur in response to variations in the pattern of neural stimulation, loading conditions, availability of substrates, and hormonal signals. The new conditions can be detected by multiple sensors, from membrane receptors for hormones and cytokines, to metabolic sensors, which detect high-energy phosphate concentration, oxygen and oxygen free radicals, to calcium binding proteins, which sense variations in intracellular calcium induced by nerve activity, to load sensors located in the sarcomeric and sub-sarcolemmal cytoskeleton. These sensors trigger cascades of signaling pathways which may ultimately lead to changes in fiber size and fiber type. Changes in fiber size reflect an imbalance in protein turnover with either protein accumulation, leading to muscle hypertrophy, or protein loss, with consequent muscle atrophy. Changes in fiber type reflect a reprogramming of gene transcription leading to a remodeling of fiber contractile properties (slow-fast transitions) or metabolic profile (glycolyticoxidative transitions). While myonuclei are in postmitotic state, satellite cells represent a reserve of new nuclei and can be involved in the adaptive response. 

Present research activity deals with the effects of experimental bed rest, considered as a model of disuse, and with the effects of training protocols in young and elderly subjects. 

3) calcium signaling for regulation of muscle fibre contraction: Calcium represents a powerful intracellular messenger in skeletal muscle fibers, being able not only to trigger contractions via binding to troponin, but also to activate protein phosphorylation or dephosphorylation via binding to calmoldulin and to activate proteolysis via calcium dependent proteases. It is easy to understand that the concentration of intracellular cytosolic free calcium concentration needs to be controlled precisely. This task is accomplished by the sarcoplasmic reticulum (SR) through calcium release and uptake systems with important contributions of cytoplasmic calcium buffers, mitochondria and sarcolemma. Skeletal muscle fibers show a pronounced specialization in the control of intracellular calcium, as different types of fibers are characterized by distinct levels of resting calcium concentration and specific kinetics of the calcium transients that accompany action potentials. Importantly, calcium transient kinetics have a direct impact on the dynamic properties of the muscle fibers. The faster time course of calcium transients contributes, together with the faster cross bridge kinetics, to determine the shorter time to peak and time to half relaxation of the isometric twitch of fast fibers. While tetanic tension sees its major determinant in the cross-bridge density and in the fraction of attached force generating cross-bridges, the amplitude of the twitch is determined by the amplitude of the calcium transient and by the calcium-sensitivity of the myofibrils. 

The present activity is focussed on the role of calsequestrin to store calcium inside the SR and to regulate the release via Ryanodine Receptors (RyR). In the figure below, depletion of SR during tetanic contractions in the presence (right) and absence (left) of calsequestrin is indicated by the downward deflection of the green line.

Selected publications (1984-2013) are classified in 7 groups:

  1. Main Reviews,
  2. Myosin Isoforms and Contractile Properties In Skeletal Muscle Fibres,
  3. Calcium Transients and E-C Coupling,
  4. NFAT Signalling and Fast-To-Slow Transformation,
  5. Akt Signalling and Hypertrophy,
  6. Muscle Dystrophy
  7. Intersarcomere Dynamics In Single Fibres

1) MAIN REVIEWS

Blaauw B, Schiaffino S, Reggiani C. Mechanisms modulating skeletal muscle phenotype. Compr Physiol. 2013;3 :1645-87.
Schiaffino S, Reggiani C. Fiber types in mammalian skeletal muscles. Physiol Rev. 2011 Oct;91(4):1447-531.
Bottinelli R, Reggiani C. Human skeletal muscle fibres: molecular and functional diversity.Prog Biophys Mol Biol. 2000;73(2-4):195-262. Citations: 311
Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996 Apr;76(2):371-423. Citations 1257

2)MYOSIN ISOFORMS AND CONTRACTILE PROPERTIES IN SKELETAL MUSCLE FIBRES

Rossi AC, Mammucari C, Argentini C, Reggiani C, Schiaffino S. Two novel/ancient myosins in mammalian skeletal muscles: MYH14 and MYH15 are expressed in extraocular muscles and muscle spindles. J Physiol. 2010 Jan 15;588(Pt 2):353-64.

Toniolo L, Cancellara P, Maccatrozzo L, Patruno M, Mascarello F, Reggiani C. Masticatory myosin unveiled: first determination of contractile parameters of muscle fibers from carnivore jaw muscles. Am J Physiol Cell Physiol. 2008 Dec;295(6):C1535-42.

Bloemink MJ, Adamek N, Reggiani C, Geeves MA. Kinetic analysis of the slow skeletal myosin MHC-1 isoform from bovine masseter muscle. J Mol Biol. 2007 Nov 9;373(5):1184-97.

Toniolo L, Maccatrozzo L, Patruno M, Pavan E, Caliaro F, Rossi R, Rinaldi C, Canepari M, Reggiani C, Mascarello F. Fiber types in canine muscles: myosin isoform expression and functional characterization. Am J Physiol Cell Physiol. 2007 May;292(5):C1915-26.

Maccatrozzo L, Caliaro F, Toniolo L, Patruno M, Reggiani C, Mascarello F. The sarcomeric myosin heavy chain gene family in the dog: analysis of isoform diversity and comparison with other mammalian species. Genomics. 2007 Feb;89(2):224-36.

Toniolo L, Patruno M, Maccatrozzo L, Pellegrino MA, Canepari M, Rossi R, D'Antona G, Bottinelli R, Reggiani C, Mascarello F. Fast fibres in a large animal: fibre types, contractile properties and myosin expression in pig skeletal muscles. J Exp Biol. 2004 May;207(Pt 11):1875-86.

Linari M, Bottinelli R, Pellegrino MA, Reconditi M, Reggiani C, Lombardi V. The mechanism of the force response to stretch in human skinned muscle fibres with different myosin isoforms. J Physiol. 2004 Jan 15;554(Pt 2):335-52.

Pellegrino MA, Canepari M, Rossi R, D'Antona G, Reggiani C, Bottinelli R. Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles. J Physiol. 2003 Feb 1;546(Pt 3):677-89.

He ZH, Bottinelli R, Pellegrino MA, Ferenczi MA, Reggiani C. ATP consumption and efficiency of human single muscle fibers with different myosin isoform composition. Biophys J. 2000 Aug;79(2):945-61.

Reggiani C, Potma EJ, Bottinelli R, Canepari M, Pellegrino MA, Stienen GJ. Chemo-mechanical energy transduction in relation to myosin isoform composition in skeletal muscle fibres of the rat. J Physiol. 1997 Jul 15;502 ( Pt 2):449-60.

Bottinelli R, Canepari M, Pellegrino MA, Reggiani C. Force-velocity properties of human skeletal muscle fibres: myosin heavy chain isoform and temperature dependence. J Physiol. 1996 Sep 1;495 ( Pt 2):573-86.

Stienen GJ, Kiers JL, Bottinelli R, Reggiani C. Myofibrillar ATPase activity in skinned human skeletal muscle fibres: fibre type and temperature dependence. J Physiol. 1996 Jun 1;493 ( Pt 2):299-307.

Bottinelli R, Canepari M, Reggiani C, Stienen GJ. Myofibrillar ATPase activity during isometric contraction and isomyosin composition in rat single skinned muscle fibres. J Physiol. 1994 Dec 15;481 ( Pt 3):663-75.

Bottinelli R, Betto R, Schiaffino S, Reggiani C. Unloaded shortening velocity and myosin heavy chain and alkali light chain isoform composition in rat skeletal muscle fibres. J Physiol. 1994 Jul 15;478 ( Pt 2):341-9.

Bottinelli R, Schiaffino S, Reggiani C. Force-velocity relations and myosin heavy chain isoform compositions of skinned fibres from rat skeletal muscle. J Physiol. 1991 Jun;437:655-72. Citations: 411

3)CALCIUM TRANSIENTS AND E-C COUPLING

Tomasi M, Canato M, Paolini C, Dainese M, Reggiani C, Volpe P, Protasi F, Nori A. Calsequestrin (CASQ1) rescues function and structure of calcium release units in skeletal muscles of CASQ1-null mice. Am J Physiol Cell Physiol. 2012 Feb;302(3):C575-86.

Canato M, Scorzeto M, Giacomello M, Protasi F, Reggiani C, Stienen GJ. Massive alterations of sarcoplasmic reticulum free calcium in skeletal muscle fibers lacking calsequestrin revealed by a genetically encoded probe. Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22326-31.

Dainese M, Quarta M, Lyfenko AD, Paolini C, Canato M, Reggiani C, Dirksen RT, Protasi F. Anesthetic- and heat-induced sudden death in calsequestrin-1-knockout mice. FASEB J. 2009 Jun;23(6):1710-20.

Paolini C, Quarta M, Nori A, Boncompagni S, Canato M, Volpe P, Allen PD, Reggiani C, Protasi F. Reorganized stores and impaired calcium handling in skeletal muscle of mice lacking calsequestrin-1. J Physiol. 2007 Sep 1;583(Pt 2):767-84.

Bertocchini F, Ovitt CE, Conti A, Barone V, Schöler HR, Bottinelli R, Reggiani C, Sorrentino V. Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles. EMBO J. 1997 Dec 1;16(23):6956-63.

4)NFAT SIGNALLING AND FAST-TO-SLOW TRANSFORMATION

Tothova J, Blaauw B, Pallafacchina G, Rudolf R, Argentini C, Reggiani C, Schiaffino S. NFATc1 nucleocytoplasmic shuttling is controlled by nerve activity in skeletal muscle. J Cell Sci. 2006 Apr 15;119(Pt 8):1604-11.

5)AKT SIGNALLING AND HYPERTROPHY

Blaauw B, Agatea L, Toniolo L, Canato M, Quarta M, Dyar KA, Danieli-Betto D, Betto R, Schiaffino S, Reggiani C. Eccentric contractions lead to myofibrillar dysfunction in muscular dystrophy. J Appl Physiol. 2010 Jan;108(1):105-11. Epub 2009 Nov 12. PubMed PMID: 19910334.

Blaauw B, Canato M, Agatea L, Toniolo L, Mammucari C, Masiero E, Abraham R, Sandri M, Schiaffino S, Reggiani C. Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation. FASEB J. 2009 Nov;23(11):3896-905.

Blaauw B,Mammucari C,Toniolo L, Agatea L,Abraham R,Sandri M,Reggiani C, Schiaffino S. Akt activation prevents the force drop induced by eccentric contractions in dystrophin-deficient skeletal muscle. Hum Mol Genet. 2008 Dec 1;17(23):3686-96.

6)MUSCLE DYSTROPHY

Randazzo D, Giacomello E, Lorenzini S, Rossi D, Pierantozzi E, Blaauw B, Reggiani C, Lange S, Peter AK, Chen J, Sorrentino V. Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity. J Cell Biol. 2013 Feb 18;200(4):523-36.

Serra F, Quarta M, Canato M, Toniolo L, De Arcangelis V, Trotta A, Spath L, Monaco L, Reggiani C, Naro F. Inflammation in muscular dystrophy and the beneficial effects of non-steroidal anti-inflammatory drugs. Muscle Nerve. 2012 Nov;46(5):773-84

Menazza S, Blaauw B, Tiepolo T, Toniolo L, Braghetta P, Spolaore B, Reggiani C, Di Lisa F, Bonaldo P, Canton M. Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy. Hum Mol Genet. 2010 Nov 1;19(21):4207-15.

Canato M, Dal Maschio M, Sbrana F, Raiteri R, Reggiani C, Vassanelli S, Megighian A. Mechanical and electrophysiological properties of the sarcolemma of muscle fibers in two murine models of muscle dystrophy: col6a1-/- and mdx. J Biomed Biotechnol. 2010;2010:981945.

Irwin WA, Bergamin N, Sabatelli P, Reggiani C, Megighian A, Merlini L, Braghetta P, Columbaro M, Volpin D, Bressan GM, Bernardi P, Bonaldo P. Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency. Nat Genet. 2003 Dec;35(4):367-71.

7)INTERSARCOMERE DYNAMICS IN SINGLE FIBRES

Edman KA, Reggiani C, Schiaffino S, te Kronnie G. Maximum velocity of shortening related to myosin isoform composition in frog skeletal muscle fibres. J Physiol. 1988 Jan;395:679-94.
Edman KA, Reggiani C. The sarcomere length-tension relation determined in short segments of intact muscle fibres of the frog. J Physiol. 1987 Apr;385:709-32.
Edman KA, Reggiani C, te Kronnie G. Differences in maximum velocity of shortening along single muscle fibres of the frog. J Physiol. 1985 Aug;365:147-63.
Edman KA, Reggiani C. Redistribution of sarcomere length during isometric contraction of frog muscle fibres and its relation to tension creep. J Physiol. 1984 Jun;351:169-98

Telethon: 'Altered calcium handling in Central Core Disease and Malignant Hyperthermia: understand molecular mechanisms and genetic background to develop innovative therapeutic interventions' 2014-2016

ESA - European Space Agency: "Preventing muscle atrophy during space flights by interfering with Akt-FoxO-Atrogin-1 signaling" 2011-2014

EU via interregio project: PANGEA - Physical Activity and Nutrition for a Good Healthy Ageing 2011-2014

FSE: via Regione Veneto: MYOSCREEN - Detection of hypertrophy induced by illegal compounds