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Laboratory of Muscle Stem Cells and Gene Regulation
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.
Proserpio V, Fittipaldi R, Ryall JG, Sartorelli V, Caretti G. The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy. Genes Dev. 2013 Jun 1;27(11):1299-312. doi: 10.1101/gad.217240.113.
Wang AH, Zare H, Mousavi K, Wang C, Moravec CE, Sirotkin HI, Ge K, Gutierrez-Cruz G, Sartorelli V. The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis.EMBO J.2013 Mar 15. doi: 10.1038/emboj.2013.54
Derfoul A, Juan AH, Difilippantonio MJ, Palanisamy N, Ried T, Sartorelli V. Decreased microRNA-214 levels in breast cancer cells coincides with increased cell proliferation, invasion and accumulation of the Polycomb Ezh2 methyltransferase. Carcinogenesis. 2011 Sep 8.
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 Apr 15;25(8):789-94.
Palacios D, Mozzetta C, Consalvi S, Caretti G, Saccone V, Proserpio V, Marquez VE, Valente S, Mai A, Forcales SV, Sartorelli V, Puri PL. TNF/p38α/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration. Cell Stem Cell. 2010 Oct 8;7(4):455-69See extended list of publications
Updated November 2. 2012