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Related Research Units

Intellectual and Developmental Disabilities Research Center Research
Genetics and Genomics Research
Gussoni Laboratory Research

Research Overview

Dr. Gussoni’s laboratory studies muscle stem cells in human and mouse tissues, with the goal of developing strategies that will slow the progression of and improve muscle function for muscular dystrophy.

Laboratory Projects:

  1. Tetraspanin CD82 in muscle stem cells and its role in normal and dystrophic muscle: CD82 is expressed in muscle stem cells and its expression is decreased in patients with Duchenne muscular dystrophy. This project will determine if CD82 upregulation is beneficial to dystrophic muscle and conversely, whether ablation of CD82 expression in dystrophic muscle worsens the disease.

  2. Bipotent progenitors (muscle or fat) in skeletal muscle: We identified progenitors in skeletal muscle that express BMPR1a and can adopt a myogenic or adipogenic fate. We are studying the downstream molecular mechanisms that regulate the fate determination of these progenitors towards muscle or fat lineages. We want to study the developmental origin of these cells and their contribution to developing and adult skeletal muscle in both normal and diseased conditions.

  3. Proteins that mediate fusion of myoblasts into myofibers: We have identified several candidate genes that significantly change in expression during muscle cell differentiation and fusion. This project studies the function of candidate genes in muscle cells and in regenerating muscle. Additionally, the candidate genes are tested for presence of mutations in patients with uncharacterized muscle disorders.

Research Background

Dr. Gussoni obtained her Ph.D. degree from the University of Milan, Italy. She moved to the United States and did her first postdoctoral fellowship at Stanford University, where she evaluated expression of dystrophin and donor cell survival in DMD patients that participated in a myoblast transfer clinical trial. She then moved to Boston Children’s Hospital for her second postdoctoral fellowship training, where she studied muscle and bone marrow stem cells and their ability to deliver dystrophin following systemic injection. She established her own laboratory at Boston Children’s Hospital in early 2000 and she is presently an Associate Professor at Harvard University. She has been a permanent member of the Muscular Dystrophy Association (USA) Scientific Advisory Committee since 2006.

Selected Publications

  1. Alexander MS, Rozkalne A, Colletta A, Spinazzola JS, Johnson S, Rahimov F, Meng H, Lawlor MW, Estrella E, Kunkel LM, Gussoni E. CD82 Is a Marker for Prospective Isolation of Human Muscle Satellite Cells and Is Linked to Muscular Dystrophies. Cell Stem Cell 19(6): 800-807. ePub Sept 15, 2016. PMID:27641304.
  2. Huang P, Schulz TJ, Beauvais A, Tseng YH and Gussoni E. Intramuscular adipogenesis is inhibited by myo-endothelial progenitors with functioning Bmpr1a signalling. Nat Commun. 2014 Jun 5;5:4063. doi: 10.1038/ncomms5063. PMID: 24898859. Balasubramanian A, Kawahara G, Gupta VA, Rozkalne A, Beauvais A, Kunkel LM and Gussoni E. Fam65b is important for formation of the HDAC6-dysferlin protein complex during myogenic cell differentiation. FASEB J. 2014 Jul;28(7):2955-69. doi: 10.1096/fj.13-246470. Epub 2014 Mar 31. PMID: 24687993.
  3. Sohn RL, Huang P, Kawahara G, Mitchell M, Guyon J, Kalluri R, Kunkel LM and Gussoni E. A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9274-9. Epub 2009 May 22. PMID: 19470472.

Publications

  1. Organoid culture promotes dedifferentiation of mouse myoblasts into stem cells capable of complete muscle regeneration. Nat Biotechnol. 2024 Sep 11. View Abstract
  2. Tropomyosin 3 (TPM3) function in skeletal muscle and in myopathy. Skelet Muscle. 2023 11 07; 13(1):18. View Abstract
  3. Tetraspanin CD82 Associates with Trafficking Vesicle in Muscle Cells and Binds to Dysferlin and Myoferlin. Adv Biol (Weinh). 2023 12; 7(12):e2300157. View Abstract
  4. Lysine methyltransferase 2D regulates muscle fiber size and muscle cell differentiation. FASEB J. 2021 11; 35(11):e21955. View Abstract
  5. Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function. Skelet Muscle. 2020 11 27; 10(1):34. View Abstract
  6. Differentiation of the human PAX7-positive myogenic precursors/satellite cell lineage in vitro. Development. 2020 06 26; 147(12). View Abstract
  7. Purification of Myogenic Progenitors from Human Muscle Using Fluorescence-Activated Cell Sorting (FACS). Methods Mol Biol. 2019; 1889:1-15. View Abstract
  8. Building immune tolerance through DNA vaccination. Proc Natl Acad Sci U S A. 2018 09 25; 115(39):9652-9654. View Abstract
  9. A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure. PLoS One. 2017; 12(12):e0189324. View Abstract
  10. Isolation of Primary Human Skeletal Muscle Cells. Bio Protoc. 2017 Nov 05; 7(21). View Abstract
  11. Exosomal Small Talk Carries Strong Messages from Muscle Stem Cells. Cell Stem Cell. 2017 01 05; 20(1):1-3. View Abstract
  12. CD82 Is a Marker for Prospective Isolation of Human Muscle Satellite Cells and Is Linked to Muscular Dystrophies. Cell Stem Cell. 2016 12 01; 19(6):800-807. View Abstract
  13. Differentiation of pluripotent stem cells to muscle fiber to model Duchenne muscular dystrophy. Nat Biotechnol. 2015 Sep; 33(9):962-9. View Abstract
  14. Isolation and immortalization of patient-derived cell lines from muscle biopsy for disease modeling. J Vis Exp. 2015 Jan 18; (95):52307. View Abstract
  15. Tissue triage and freezing for models of skeletal muscle disease. J Vis Exp. 2014 Jul 15; (89). View Abstract
  16. POMK mutations disrupt muscle development leading to a spectrum of neuromuscular presentations. Hum Mol Genet. 2014 Nov 01; 23(21):5781-92. View Abstract
  17. Intramuscular adipogenesis is inhibited by myo-endothelial progenitors with functioning Bmpr1a signalling. Nat Commun. 2014 Jun 05; 5:4063. View Abstract
  18. Fam65b is important for formation of the HDAC6-dysferlin protein complex during myogenic cell differentiation. FASEB J. 2014 Jul; 28(7):2955-69. View Abstract
  19. Mouse regenerating myofibers detected as false-positive donor myofibers with anti-human spectrin. Hum Gene Ther. 2014 Jan; 25(1):73-81. View Abstract
  20. G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo. FEBS J. 2013 Dec; 280(23):6097-113. View Abstract
  21. Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat. Nature. 2013 Mar 21; 495(7441):379-83. View Abstract
  22. Myotubularin-deficient myoblasts display increased apoptosis, delayed proliferation, and poor cell engraftment. Am J Pathol. 2012 Sep; 181(3):961-8. View Abstract
  23. Human fetal skeletal muscle contains a myogenic side population that expresses the melanoma cell-adhesion molecule. Hum Mol Genet. 2012 Aug 15; 21(16):3668-80. View Abstract
  24. Isolation and characterization of human fetal myoblasts. Methods Mol Biol. 2012; 798:3-19. View Abstract
  25. ß4 integrin marks interstitial myogenic progenitor cells in adult murine skeletal muscle. J Histochem Cytochem. 2012 Jan; 60(1):31-44. View Abstract
  26. Carbamylated erythropoietin does not alleviate signs of dystrophy in mdx mice. Muscle Nerve. 2011 Jan; 43(1):88-93. View Abstract
  27. Inefficient dystrophin expression after cord blood transplantation in Duchenne muscular dystrophy. Muscle Nerve. 2010 Jun; 41(6):746-50. View Abstract
  28. A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion. Proc Natl Acad Sci U S A. 2009 Jun 09; 106(23):9274-9. View Abstract
  29. Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation. J Cell Sci. 2008 May 01; 121(Pt 9):1426-34. View Abstract
  30. Myogenic reprogramming of retina-derived cells following their spontaneous fusion with myotubes. Dev Biol. 2007 Nov 15; 311(2):449-63. View Abstract
  31. Stem and progenitor cells in skeletal muscle development, maintenance, and therapy. Molecular Therapy. 2007; 15(5):867-77. View Abstract
  32. Stem and progenitor cells in skeletal muscle development, maintenance, and therapy. Mol Ther. 2007 May; 15(5):867-77. View Abstract
  33. C6ORF32 is upregulated during muscle cell differentiation and induces the formation of cellular filopodia. Dev Biol. 2007 Jan 01; 301(1):70-81. View Abstract
  34. Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin. J Cell Biol. 2006 Oct 09; 175(1):99-110. View Abstract
  35. Melanoma cell adhesion molecule is a novel marker for human fetal myogenic cells and affects myoblast fusion. J Cell Sci. 2006 Aug 01; 119(Pt 15):3117-27. View Abstract
  36. Myogenic potential of muscle side and main population cells after intravenous injection into sub-lethally irradiated mdx mice. J Histochem Cytochem. 2005 Jul; 53(7):861-73. View Abstract
  37. Human myoblasts and muscle-derived SP cells. Methods Mol Med. 2005; 107:97-110. View Abstract
  38. Demystifying SP cell purification: viability, yield, and phenotype are defined by isolation parameters. Exp Cell Res. 2004 Aug 01; 298(1):144-54. View Abstract
  39. Role of bone marrow cell trafficking in replenishing skeletal muscle SP and MP cell populations. J Cell Sci. 2004 Apr 15; 117(Pt 10):1979-88. View Abstract
  40. Stem cell therapy for muscular dystrophy. Expert Opin Biol Ther. 2004 Jan; 4(1):1-9. View Abstract
  41. Statistical challenges in functional genomics. Statistical Science. 2003; 18:33-70. View Abstract
  42. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J Clin Invest. 2002 Sep; 110(6):807-14. View Abstract
  43. Muscular dystrophies and stem cells: a therapeutic challenge. Cytotherapy. 2002; 4(6):513-9. View Abstract
  44. Recent advances in and therapeutic potential of muscle-derived stem cells. J Cell Biochem Suppl. 2002; 38:80-7. View Abstract
  45. Evaluating human T cell receptor gene expression by PCR. Curr Protoc Immunol. 2001 May; Chapter 10:10.26.1-10.26.14. View Abstract
  46. T cell receptor BV gene rearrangements in the spinal cords and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Neurobiol Dis. 1999 Oct; 6(5):392-405. View Abstract
  47. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999 Sep 23; 401(6751):390-4. View Abstract
  48. The fate of individual myoblasts after transplantation into muscles of DMD patients. Nat Med. 1997 Sep; 3(9):970-7. View Abstract
  49. Myoblast implantation in Duchenne muscular dystrophy: the San Francisco study. Muscle Nerve. 1997 Apr; 20(4):469-78. View Abstract
  50. Evaluating T-cell receptor gene expression by PCR. Current Protocols in Immunology. 1997; 10.26.1-10.26.14. View Abstract
  51. A method to codetect introduced genes and their products in gene therapy protocols. Nat Biotechnol. 1996 Aug; 14(8):1012-6. View Abstract
  52. The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives. J Biol Chem. 1996 Feb 02; 271(5):2724-30. View Abstract
  53. Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy. Science. 1995 Nov 03; 270(5237):819-22. View Abstract
  54. Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex. Nat Genet. 1995 Nov; 11(3):266-73. View Abstract
  55. Specific T cell receptor gene rearrangements at the site of muscle degeneration in Duchenne muscular dystrophy. J Immunol. 1994 Nov 15; 153(10):4798-805. View Abstract
  56. Dystrophin abnormalities in Duchenne and Becker dystrophy carriers: correlation with cytoskeletal proteins and myosins. J Neurol. 1993 Sep; 240(8):455-61. View Abstract
  57. Analysis of the T cell repertoire using the PCR and specific oligonucleotide primers. Biotechniques. 1992 May; 12(5):728-35. View Abstract
  58. Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation. Nature. 1992 Apr 02; 356(6368):435-8. View Abstract
  59. Dystrophin analysis in Duchenne and Becker muscular dystrophy carriers: correlation with intracellular calcium and albumin. Ann Neurol. 1990 Nov; 28(5):674-9. View Abstract

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