Manzoni / Gandolfi

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PhD Student: Elena Franca Maria Manzoni graduated in Veterinary Biotechnology Master’s Degree at the University of Milan in July 2015 with the final mark of 110/110 cum laude. In 2012 she worked as an undergraduate student at the laboratory of Biomedical Sciences, University of Ulster under the supervision of Professor Colum Walsh on the epigenetic mechanisms regulating gene expression. In 2014 she worked as an intern at Genomnia srl where she learned next generation sequencing methods and bioinformatics analysis. This experience led to her graduation thesis entitled: ”Next Generation Sequencing analysis of human somatic cells exposed to 5-azacytidine:expression and methylation profiles“.

Tutor: Fulvio Gandolfi received his degree in Veterinary Medicine in 1982 at the University of Milan. He moved to the AFRC in Cambridge UK from 1985 to 1988 where he developed the first method for the in vitro culture of animal zygotes. He has been a visiting Professor at Monash University in Melbourne and at Adelaide University. At present he is Full Professor of Anatomy and Embryology at the Faculty of Veterinary Medicine in Milan (Italy). He works on the reproductive biology of farm animals and on the use of epigenetic mechanisms to direct and modify cell fate. He is Vice President of ICAR (International Congress of Animal Reproduction), a founding member of UNISTEM, the Centre for the Study of Stem Cells of the University of Milan, Member of the Board of Governors of the International Embryo Transfer Society. Since 2002 is Co-Editor in Chief of Theriogenology and he became Editor-in-Chief in 2013. An updated list of his research papers can be found on Google Scholar

Research Project: Molecular and cellular mechanisms regulating epigenetic cell conversion.

We have recently developed a protocol by which is possible to convert adult somatic cells into a different cell type using the epigenetic modifier 5-azacytidine (5-aza-CR).

This molecule is able to push the cells to a less committed state, increasing their plasticity. Once cells have entered into this higher plasticity window, they can easily be directed towards a different phenotype if they are exposed to specific differentiation stimuli.
This direct approach is highly efficient, it does not require any transgenic modification, it is patient-specific and therefore avoids allogeneic rejection. For all these reason cells derived with this approach (defined epiCC) may represent a very promising tool for the regenerative medicine of several and diverse degenerative diseases.

Aim of this project is to investigate the mechanisms that allowed the epigenetic erasing of cell phenotype and the acquisition of a high plasticity state. The expected results will expand our knowledge on the effect exerted by 5-aza-CR, further setting this technique as a robust and powerful tool for regenerative medicine and cell therapy.

A multidisciplinary approach will be used and will involve advanced techniques of stem cell culture, cell and molecular biology, methylation studies, immunofluorescence, electron and confocal microscopy, cellular mechanosensing, cell and exosome mediated interactions.