PhD Student Fellow
2014-2016: Master’s degree in Cellular and Molecular Biology, University of Bari “Aldo Moro”, Bari (Italy). Final mark: 110/110 magna cum laude.
2011-2014: Bachelor’s Degree in Biological Sciences, University of Bari “Aldo Moro”, Bari (Italy).
2006-2011: High School Degree, High school (specializing in classical studies) “Isabella Morra” (Senise, PZ, Italy).
October 2018 – present: Ph.D. studentship in Dr. Nicassio’s laboratory. University of Milano (Italy) . Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milano (Italy).
Research topic: study of the role of TDMD in breast cancer models.
March 2017 – September 2018: Research fellow in Dr. Nicassio’s laboratory. Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milano (Italy).
Research topic: study of degradation mechanism of microRNA regulation.
November 2015 – November 2016: Master’s degree internship. University of Bari “Aldo Moro”, Bari (Italy) – Department of Biology. Supervisors: Dr. Luigi Viggiano and Prof. Beatrice Nico.
Research topic:Neuronal differentiation and characterization of iPSC from a DMD patient .
Target-Directed miRNA degradation in human cancer
MicroRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that function in controlling the expression of genes. Levels of miRNAs are critical for their functions: the higher the number of miRNA molecules available, the stronger the effects on their target genes. In our laboratory we are investigating the mechanisms that control miRNA levels with a particular focus on miRNA degradation.
Understanding the mechanisms that control miRNA levels is fundamental to comprehend the molecular basis of miRNA alterations in human cancer and to restore miRNA levels in tumors for therapeutic purposes.
A novel mechanism in control of miRNA levels has been recently described, which involves specific transcripts able to interact with miRNAs and then induce miRNA degradation. This mechanism, called Target-Directed miRNA degradation (TDMD), has been recently shown to function in vertebrates with endogenous transcripts, but its implications in human physiopathology are still unknown. We have previously shown that Serpine1 is an endogenous TDMD transcript (Ghini and Rubolino et al., Nat Comm 2018). Serpine1 uses TDMD to control levels and activity of two related miRNAs, miR-30b/c, in murine fibroblasts during serum response. Whether the TDMD mechanisms is also implicated in human cancer is currently unknown.
My aim is to investigate the TDMD hypothesis in human cancer. Using a computational approach, we have identified several TDMD transcripts in the human genome, with many TDMD transcripts overexpressed in tumors, classified as canonical cancer genes (Cancer Gene Census) or frequently involved in genomic rearrangements (amplified or deleted). I am using molecular and genetic approaches (i.e. CRISPR/Cas9 mediated genome engineering) to manipulate TDMD mechanism directly and investigate the effects afforded by miRNA degradation in cancer cells. Our preliminary results suggest that TDMD could be actually used by cancer cells to keep the activity of miRNAs low and provide selective advantage in various cancer phenotypes.
This project is supported by an AIRC fellowship to Dr. Rubolino .and the AIRC Investigator Grant to Dr. Nicassio
- Ghini F.*, Rubolino C.*, Climent-Salarich M., Simeone I., Marzi M.J., Nicassio F.,” Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism”. Nature Communications. 2018 Aug 7;9(1):3119. DOI: 10.1038/s41467-018- 05182-9. * = Co-first Author
- Ruggieri S., Viggiano L., Annese T., Rubolino C., Gerbino A., Dezio R., Corsi P., Tamma R., Ribatti D., Errede M, Operto F., Margari L., Resta N., Ditommaso S., Rosati J., Trojano M., Nico B., “DP71 and SERCA2 alteration in human neurons of a Duchenne muscular dystrophy patient”. Stem Cell Res Ther. 2019 Jan 15;10(1):29. doi: 10.1186/s13287-018-1125-5