I studied Medical Biotechnologies (BSc) at the University of Bologna (Italy), before undertaking a PhD in Molecular Biology at the University of Ferrara (Italy). For my PhD project in collaboration with Dr Richard Wade-Martins, I developed vectors for gene therapy applications based on the herpes simplex type-1 virus and providing extra-chromosomal vector retention. I then completed a 2-year post-doctoral position in Dr Wade-Martins lab and was awarded in 2010 a Research Fellowship by Ataxia UK, which was renewed in 2012.
Senior Postdoctoral Research Scientist
My research focuses on Friedreich’s ataxia (FRDA), a progressive neurodegenerative disorder with poor prognosis which represents the most common form of recessive ataxia. FRDA is caused by abnormal triplet repeat expansions (GAA), which silence expression of the frataxin gene (FXN) leading to reduced cellular levels of frataxin, a nuclear-encoded mitochondrial protein essential for life. The mechanism through which expanded GAA repeats silence FXN expression is still not well understood.
During the last few years, I have established in our laboratory several lines of research aimed at a better understanding of the GAA-mediated mechanism of FXN silencing as well as developing viable treatments for FRDA. Our approaches to achieve this are based on the generation, characterization and use of genomic-reporter models of FRDA, which provide physiologically-relevant FXN expression by carrying the whole genomic DNA locus of the FXN gene. Our FRDA cell models also carry expanded GAA repeats, which recapitulate the epigenetic modifications and repression of gene expression seen in FRDA, as we have shown in a recent publication on Human Molecular Genetics. We have recently used one of these cell models to screen a library of compounds (in collaboration with Dr Angela Russell) and have identified a new promising small molecule for the treatment of FRDA. Recently, we have also established a new reporter model of FRDA which allows the real-time visualization of FXN transcription in live cells and at single-cell resolution (Ana Silva, visiting PhD student), therefore providing a powerful tool to dissect the mechanism of GAA-mediated FXN repression observed in FRDA.
The infectious BAC genomic DNA expression library: a high capacity vector system for functional genomics.
Lufino MMP. et al, (2016), Sci Rep, 6
Expanded GAA repeats impair FXN gene expression and reposition the FXN locus to the nuclear lamina in single cells.
Silva AM. et al, (2015), Hum Mol Genet, 24, 3457 - 3471
A GAA repeat expansion reporter model of Friedreich's ataxia recapitulates the genomic context and allows rapid screening of therapeutic compounds.
Lufino MMP. et al, (2013), Hum Mol Genet, 22, 5173 - 5187
Episomal transgene expression in pluripotent stem cells.
Lufino MMP. et al, (2011), Methods Mol Biol, 767, 369 - 387
Long-term physiologically regulated expression of the low-density lipoprotein receptor in vivo using genomic DNA mini-gene constructs.
Hibbitt OC. et al, (2010), Mol Ther, 18, 317 - 326