Vittorio Sartorelli, M.D.
Laboratory of Muscle Stem Cells and Gene Regulation
Building 50, Room 1351
50 South Drive
Bethesda, MD 20814
We study the cellular and molecular mechanisms subtending specification, differentiation, and regeneration of skeletal muscle cells. We pursue these studies by combining cellular and molecular biological approaches, genomic and proteomic-based systems-biology, bioinformatics, and animal models.
Specific areas of interest include:
Transcriptional Regulation of Skeletal Muscle Differentiation
Biochemical and molecular characterization of individual transcription factors, chromatin regulators, and epigenetic marks during skeletal muscle specification and development. Genetic manipulation of the individual components is obtained by whole-body and conditional gene ablation in developing embryos and adult mice.
Regulatory Circuitry in Skeletal Muscle Cells
Integration of signaling pathways and logics of transcription factors and chromatin regulators. General operating principles and gene network modeling are developed based on genome-wide experimental data.
Regeneration of Adult Skeletal Muscle
Following injury, skeletal muscle vigorously regenerates. The cellular and molecular mechanisms underlying regeneration are investigated in animals in which individual genetic components have been ablated by homologous recombination.
Metabolic Role of Skeletal Muscle
Skeletal muscle is responsible for insulin-mediated glucose uptake. The role of skeletal muscle in mediating the metabolic effects of hypercaloric diet and calorie-restriction is investigated.
Objectives: The ultimate goal of our studies is to provide a conceptual and practical framework contributing to the diagnosis and treatment of human diseases affecting skeletal muscles.
In 1990, Dr.Sartorelli was appointed Assistant Professor in the Department of Chemistry at the University of Brescia, School of Medicine. In 1993, he joined the Department of Biochemistry and Molecular Biology of the Keck School of Medicine, University of Southern California as an Assistant Professor and was recruited in 1999 at the National Institutes of Health to head the Muscle Gene Expression Group within the Laboratory of Muscle Biology of the Intramural Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Mousavi K, Zare H, Wang AH, Sartorelli V. Polycomb protein Ezh1 promotes RNA polymerase II elongation. Mol Cell. 2012;45(2):255-62.
Juan AH, Derfoul A, Feng X, Ryall JG, Dell'Orso S, Pasut A, Zare H, Simone JM, Rudnicki MA, Sartorelli V. Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells. Genes Dev. 2011;25(8):789-94.
Juan AH, Kumar RM, Marx JG, Young RA, Sartorelli V. Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells. Mol Cell. 2009;36(1):61-74.
Fulco M, Cen Y, Zhao P, Hoffman EP, McBurney MW, Sauve AA, Sartorelli V. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell. 2008;14(5):661-73.
Caretti G, Schiltz RL, Dilworth FJ, Di Padova M, Zhao P, Ogryzko V, Fuller-Pace FV, Hoffman EP, Tapscott SJ, Sartorelli V. The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Dev Cell. 2006;11(4):547-60.