A5057520496- Muscle Physiology and Disorders
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Mesenchymal stem cell research
- Adipose Tissue and Metabolism
- Tissue Engineering and Regenerative Medicine
- Cardiac electrophysiology and arrhythmias
- Parathyroid Disorders and Treatments
- Exercise and Physiological Responses
- Magnesium in Health and Disease
- Ion Channels and Receptors
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Muscle activation and electromyography studies
- Cellular transport and secretion
- Neurobiology and Insect Physiology Research
- Angiogenesis and VEGF in Cancer
- Planarian Biology and Electrostimulation
- Erythrocyte Function and Pathophysiology
- Periodontal Regeneration and Treatments
- Regulation of Appetite and Obesity
- Nerve injury and regeneration
- Apelin-related biomedical research
University of Siena
2016-2025
Azienda Ospedaliera Universitaria Senese
2014-2019
Institute of Molecular Medicine
2013
University of Rome Tor Vergata
2007-2009
Sapienza University of Rome
2005
Mesenchymal stem cells (MSCs) are adult multipotent able to differentiate toward mature mesodermal lineages. In spite of more than a decade investigation, little is known about the molecular mechanisms regulating undifferentiated state and identity distinct functional subpopulations in these cells. Transcription factors that regulate maintenance pluripotent embryonic cells, including NANOG, SOX2, OCT4, have been proposed play similar role also although with conflicting results. We performed...
Obscurin is a large myofibrillar protein that contains several interacting modules, one of which mediates binding to muscle-specific ankyrins. Interaction between obscurin and the ankyrin sAnk1.5 regulates organization sarcoplasmic reticulum in striated muscles. Additional isoforms, ankB ankG, are localized at subsarcolemma level, they contribute dystrophin β-dystroglycan costameres. In this paper, we report mice deficient for obscurin, was displaced from its localization M band, whereas...
A missense mutation in the calsequestrin-1 gene (CASQ1) was found a group of patients with myopathy characterized by weakness, fatigue, and presence large vacuoles containing characteristic inclusions resulting from aggregation sarcoplasmic reticulum (SR) proteins. The affects conserved aspartic acid position 244 (p.Asp244Gly) located one high-affinity Ca(2+) -binding sites CASQ1 alters kinetics release muscle fibers. Expression mutated protein COS-7 cells showed markedly reduced ability...
Here, we report the identification of three novel missense mutations in calsequestrin-1 (CASQ1) gene four patients with tubular aggregate myopathy. These CASQ1 affect conserved amino acids position 44 (p.(Asp44Asn)), 103 (p.(Gly103Asp)), and 385 (p.(Ile385Thr)). Functional studies, based on turbidity dynamic light scattering measurements at increasing Ca2+ concentrations, showed a reduced -dependent aggregation for protein containing p.Asp44Asn p.Gly103Asp slight increase p.Ile385Thr....
A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and one healthy relative. This is nucleotide away from previously reported (c.5160delC) that patients asymptomatic carriers three Bulgarian families with muscular dystrophy, indicating low penetrance the frameshift mutations. Given these similarities, we believe mutations alone can be causative without full penetrance. Moreover, comparative analysis clinical...
We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution ankyrin B (ankB), disorganization the subsarcolemmal microtubules, and reduced localization dystrophin at costameres. In addition, these have impaired running endurance increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach physiological, morphological, structural studies in which further characterize muscles KO...
In rats, various growth factors and hormones, as well partial hepatectomy (PH) are able to trigger the proliferative response of hepatocytes. Although recent evidence highlights important role thyroid hormones status in regulating liver cells vitro vivo models, mechanism involved pro-proliferative effects is still unclear. Here we have investigated how rats made hypo- hyperthyroid after prolonged treatment respectively with propylthiouracil (PTU) triiodothyronine (T3), affects regeneration...
In adult skeletal muscles, 2 junctophilin isoforms (JPH1 and JPH2) tether the sarcoplasmic reticulum (SR) to transverse tubule (T-tubule) membranes, generating stable membrane contact sites known as triads. JPHs are anchored of SR by a C-terminal transmembrane domain (TMD) bind T-tubule through their cytosolic N-terminal region, which contains 8 lipid-binding (MORN) motifs. By combining expression GFP-JPH1 deletion mutants in muscle fibers with vitro biochemical experiments, we investigated...
Ca2+ release, which is necessary for muscle contraction, occurs at the j-SR (junctional domain of sarcoplasmic reticulum). It requires assembly a large multiprotein complex containing RyR (ryanodine receptor) and additional proteins, including triadin calsequestrin. The signals drive these proteins to how they assemble form this are poorly understood. To address aspects questions we studied localization, dynamic properties molecular interactions triadin. We identified three regions, named...
Abstract Biological roles of obscurin and its close homolog Obsl1 (obscurin-like 1) have been enigmatic. While is highly expressed in striated muscles, found ubiquitously. Accordingly, mutations linked to myopathies, whereas result 3M-growth syndrome. To further study unique redundant functions these closely related proteins, we generated characterized knockouts. Global knockouts are embryonically lethal. In contrast, skeletal muscle-specific show a benign phenotype similar Only deletion...
Microvascular pericytes (PCs) are considered the adult counterpart of embryonic mesoangioblasts, which represent a multipotent cell population that resides in dorsal aorta developing embryo. Although PCs have been isolated from several organs and tissues, it is still controversial whether different tissues exhibit distinct differentiation potentials. To address this point, we investigated potentials isogenic human cultured skeletal (sk-hPCs) smooth muscle (sm-hPCs). We found both sk-hPCs...
Pericytes (PCs) have been recognized for a long time only as structural cells of the blood vessels. The identification tight contacts with endothelial and ability to interact surrounding through paracrine signaling revealed additional functions PCs in maintaining homeostasis perivascular environment. got front page, late 1990s, after characterization new embryonic cell population, mesoangioblasts, from which present adult organism are thought derive. From these studies, it was clear that...
Abstract Two likely causative mutations in the RYR1 gene were identified two patients with myopathy tubular aggregates, but no evidence of cores or core‐like pathology on muscle biopsy. These clinically evaluated and underwent routine laboratory investigations, electrophysiologic tests, biopsy magnetic resonance imaging (MRI). They reported stiffness muscles following sustained activity cold exposure had serum creatine kinase elevation. The (p.Thr2206Met p.Gly2434Arg, patient 1 2,...
Obscurin is a giant sarcomeric protein expressed in striated muscles known to establish several interactions with other proteins of the sarcomere, but also sarcoplasmic reticulum and costameres. Here, we report experiments aiming better understand contribution obscurin skeletal muscle fibers, starting detailed characterization diaphragm function, which previously reported be most affected (
Tubular aggregate myopathy (TAM) is a rare characterized by muscle weakness and myalgia. Muscle fibers from TAM patients show characteristic accumulation of membrane tubules that contain proteins the sarcoplasmic reticulum (SR). Gain-of-function mutations in STIM1 ORAI1, key participating Store-Operated Ca