Giulio Cossu

Biography

Giulio Cossu (GC) is recognized for his pioneering work on skeletal myogenesis and for the first cell therapy trial with stem cells for muscular dystrophy.

He originally showed that neural tube (Vivarelli and Cossu, Dev. Biol. 1986) and, subsequently, dorsal ectoderm (Cossu et al., Development 1996) activate, through different Wnts, distinct myogenic programs in epaxial and hypaxial somitic progenitors, a notion now in developmental biology textbooks. He also pioneered studies on myogenic cell heterogeneity (Cossu and Molinaro, Curr. Topics Dev. Biol. 1987) by showing intrinsic differences among embryonic, foetal and adult myogenic progenitors (Biressi et al. Dev. Biol. 2007) whose molecular basis he recently elucidated (Messina et al. Cell 2010): these studies outlined an unforeseen parallelism with the hematopoietic system, supporting the idea that at least some tissues of developing mammals are built in subsequent stages by different families of progenitors.

In collaboration with M. Buckingham laboratory, Giulio elucidated the hierarchy of the different myogenic regulatory factors (Tajbakhsh et al. Cell 2007) and also identified unexpected expression of one of these factors, Myf5 in non-somitic progenitors such as the neuroectoderm (Tajbakhsh et al. Neuron 1994) and the lateral mesoderm (Salvatori et al. J. Cell Sci. 2005). These observations led to the identification of a bone-marrow derived, circulating myogenic progenitor cell in adult mice (Ferrari et al. Science 1998) whose embryonic precursors were later identified in the dorsal aorta (De Angelis et al. J Cell Biol. 1999). These cells, named mesoangioblasts, are able to proliferate in vitro and contribute to mesoderm tissues upon transplantation (Minasi et al. 2002). Mesoangioblasts were used for the first successful cell therapy protocols of   muscular dystrophy in mice and dogs (Sampaolesi et al. Science 2003; Nature, 2006). After characterization of human mesoangioblasts as a subset of muscle pericytes (Dellavalle et al. Nature Cell Biol. 2007) whose lineage was traced in mice (Dellavalle et al. Nature Comm. 2011), these cells were used by GC for a “first in man” phase I/II clinical trial based upon allo-transplantation of donor mesoangioblasts from an HLA-identical donor in patients affected by Duchenne muscular dystrophy. The trial started in March 2011 and is currently in progress with encouraging results in Giulio's previous Institution. Ongoing research focuses on the development of Human Artificial Chromosomes encoding the dystrophin locus which was tested successfully in dystrophic mice (Tedesco et al. Sci. Transl. Med. 2011) and is currently being further developed by inserting additional cDNA that would enhance the efficacy of human DMD mesoangioblasts for autologous cell therapy (i.e. an excisable immortalizing cassette, multiple copies of dystrophin cDNA and an inducible myogenic factor). In parallel iPS cell derived mesoangioblasts (Tedesco et al. Sci. Transl. Med. 2012) have been derived and tested for models of muscular dystrophy where the endogenous number of progenitors may be exhausted or insufficient. Overall , Giulio's research activity is characterized by the unique ability to combine work in developmental biology with cell therapy, successfully translating results obtained in mammalian embryos into clinical protocols in patients.

Giulio is author of almost 200 peer-reviewed publications; he has been invited as speaker in most meetings on myogenesis and stem cells and has organized EMBO workshops and Gordon Conferences on this topic. He receives funding from many national and international agencies, such as Telethon, Duchenne Parent Project, Human Frontiers Science Organization, European Community, European Research Council and others.

Qualifications

Giulio Cossu received his MD degree from the University of Rome in 1997. He trained as a Fogarty post-doctoral at the Wistar Institute, University of Pennsylvania (1980-83), and then became Associate Professor at the Dept. of Histology and Medical Embryology of the University of Rome "La Sapienza". In 1991 GC was promoted full Professor and in 1993-4 was a visiting professor at the Pasteur Institute in Paris. In 2000 he was appointed Director of the “Stem Cell Research Institute” of the Hospital San Raffaele in Milan. In 2003 he was appointed as Scientific Coordinator of the newly created San Raffaele Biomedical Science Park of Rome, while maintaining is position in Milan. Since 2005 he is Professor of Histology and Embryology at the University of Milan. In 2008, he was appointed Director of the newly created San Raffaele Division of Regenerative Medicine. In 2012 GC became Professor of Human Stem cell Biology at University College London, and in September 2013 Constance Thornley Professor of Regenerative Medicine at the University of Manchester.