Davide Gabellini

Research Focus

Our primary research interest is to characterise the molecular underpinnings of tissue-specific alternative splicing and delineate the mechanisms by which these become subverted in disease using facioscapulohumeral muscular dystrophy (FSHD) as a paradigm. FSHD is the third most important hereditary disease of muscle. It is not caused by a classical mutation within a protein-coding gene. Instead, our results suggest that FSHD is due to an epigenetic alteration causing transcriptional de-repression of selective genes.

We have found that over-expression of the gene FRG1 causes a muscular dystrophy with features characteristic of the human disease in mouse. FRG1 is a nuclear protein and several lines of evidence suggest it is involved in pre-mRNA splicing. We have found that in muscle of FRG1 transgenic mice and FSHD patients, specific pre-mRNAs undergo aberrant alternative splicing.

Collectively, our results suggest that FSHD results from inappropriate over-expression of FRG1, which leads to abnormal alternative splicing of specific pre-mRNAs. We are conducting a detailed study of this model to provide novel insights into the molecular pathogenesis of FSHD and for the evaluation of therapeutic strategies.


  1. Gabellini, D., D’Antona, G., Moggio, M., Prelle, A., Zecca, C., Adami, R., Angeletti, B., Ciscato, P., Pellegrino, M.A., Bottinelli, R., Green, M.R., Tupler, R. (2006). Facioscapulohumeral Muscular Dystrophy in Transgenic Mice by Over-Expression of FRG1. Nature 439, 973-977.
  2. Gabellini, D., Green, M.R., Tupler, R. (2004). When enough is enough: genetic diseases associated with transcriptional derepression. Current Opinion in Genetics and Development 14, 301-307.
  3. Tupler, R., Gabellini, D. (2004). Molecular basis of facioscapulohumeral muscular dystrophy. Cellular and Molecular Life Sciences 61, 557-566.
  4. Gabellini, D., Tupler, R., Green, M.R. (2003). Transcriptional derepression as a cause of genetic diseases. Current Opinion in Genetics and Development 13, 239-245.
  5. Gabellini, D., Green, M.R., Tupler, R. (2002). Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell 110, 339-348.

Key lab techniques: mouse transgenics, nuclear extract preparation and fractionation, virus infection, transient and stable transfection, in vivo reporter gene analysis, ChrIP analysis, one and two hybrid screening, protein:protein interaction, RNAi by short hairpin (sh)RNAs.

Key lab reagents: plasmid, retroviral and lentiviral vectors for shRNA; plasmid and retroviral TAP-tag vectors; recombinant adenoviral vectors; mouse models of muscular dystrophy.

Lab contact: gabellini.davide@hsr.it

Lab website: www.unisr.it/view.asp?id=5178