Vittorio Sartorelli, M.D.
Laboratory of Muscle Stem Cells and Gene Regulation
Skeletal muscle hosts stem cells (called Muscle Stem Cells or MuSCs) that sustain muscle growth, preserve homeostasis, and repair injuries occurring in muscle degenerative disease or trauma. Our laboratory studies how MuSCs acquire their identity during development and how their behavior is regulated during muscle regeneration and aging. We approach these questions by generating, analyzing, and integrating genomic, epigenomic, transcriptomic, and metabolomic datasets.
Specific areas of interest include:
Transcriptional Regulation of Skeletal Muscle Differentiation
Our research considers the biochemical and molecular characterization of individual transcription factors, chromatin regulators, and epigenetic marks during skeletal muscle specification and development. The 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
We study the integration of signaling pathways and the logics of transcription factors and chromatin regulators. We develop general operating principles and conduct gene network modeling based on genome-wide experimental data.
Regeneration of Adult Skeletal Muscle
Following injury, skeletal muscle vigorously regenerates. We investigate the cellular and molecular mechanisms underlying regeneration in animals in which individual genetic components have been ablated by homologous recombination.
Metabolic Regulation of Epigenetics
As satellite cells exit from quiescence during muscle regeneration, they are accompanied by changes in their metabolic state. We investigate the molecular connection between metabolism and epigenetic modification of chromatin that accompanies the transition from quiescence to proliferation and differentiation of muscle precursors.
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.
Dr. Vittorio Sartorelli received his M.D. from the University of Brescia, Italy and completed a residency in oncology at the University of Milan, Italy. He joined the Genetics Department and the Department of Medicine of the Stanford University for his postdoctoral education. 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. In 1999, he was recruited 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 (NIAMS) within the National Institutes of Health. He is currently the Chief of the Laboratory of Muscle Stem Cells & Gene Regulation and the NIAMS Deputy Scientific Director.
- Dell'Orso S, Juan AH, Ko KD, Naz F, Perovanovic J, Gutierrez-Cruz G, Feng X, Sartorelli V. Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions. Development. 2019;146(12).
- Tsai PF, Dell'Orso S, Rodriguez J, Vivanco KO, Ko KD, Jiang K, Juan AH, Sarshad AA, Vian L, Tran M, Wangsa D, Wang AH, Perovanovic J, Anastasakis D, Ralston E, Ried T, Sun HW, Hafner M, Larson DR, Sartorelli V. A Muscle-Specific Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription In trans. Mol Cell. 2018;71(1):129-141.e8.
- García-Prat L, Perdiguero E, Alonso-Martín S, Dell'Orso S, Ravichandran S, Brooks SR, Juan AH, Campanario S, Jiang K, Hong X, Ortet L, Ruiz-Bonilla V, Flández M, Moiseeva V, Rebollo E, Jardí M, Sun HW, Musarò A, Sandri M, Del Sol A, Sartorelli V, Muñoz-Cánoves P. FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age. Nat Cell Biol. 2020;22(11):1307-1318.
- Wang AH, Juan AH, Ko KD, Tsai PF, Zare H, Dell'Orso S, Sartorelli V. The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Proteins. Mol Cell. 2017;68(2):398-413.e6.
- Ryall JG, Dell'Orso S, Derfoul A, Juan A, Zare H, Feng X, Clermont D, Koulnis M, Gutierrez-Cruz G, Fulco M, Sartorelli V. The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells. Cell Stem Cell. 2015;16(2):171-83.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on Monday, July 26, 2021