Bldg. 2, Level 3, 3204 - WS 17
I graduated in Biological Science in Italy with an experimental thesis at the Institute of Molecular Biology and Pathology of the Italian National Research Council (CNR) joining the research group of Dr. Degrassi Francesca. During my Bachelor’s degree, I explored the therapeutic potential of the kinetochore (KT) protein Hec1 (Highly Expressed in Cancer protein 1) as a molecular target to produce massive chromosome missegregation and cell death in cancer cells. Hec1 mediates KT–microtubule (MT) attachments at mitosis, as constituent of the Ndc80 complex, and is upregulated in various cancer types. I expressed Hec1 fused with an enhanced green fluorescent protein (EGFP) at its N-terminus MT-interaction domain in HeLa cells and showing that expression of this modified Hec1, localized at KTs, blocks cell proliferation and promotes apoptosis in tumor cells.
Through western blot analysis, for apoptotic markers, and Immunofluorescence analysis, for studying microtubules-KT attachment dynamics, I have demonstrated that the overexpression of GFP-Hec1 is extremely potent in tumor cell killing and more efficient than siRNA-induced Hec1 depletion. Strikingly, normal cells showed no apparent cell proliferation defects or cell death following EGFP-Hec1 expression, while Live-cell imaging highlighted in cancer cells a massive chromosome missegregation, due to multipolar spindles, leading to cancer cell death after a prolonged mitotic arrest. I showed that EGFP-Hec1 over-expression is able to increase KT–MT attachment stability, providing a molecular explanation for the abnormal spindle architecture and the cytotoxic activity of this modified protein.
Within this project, I also had the opportunity to have my in-vitro observation translated in-vivo thanks to a collaboration with the Experimental Chemotherapy Laboratory of the Regina Elena National Cancer Institute in Rome, Italy. Consistent with my cell culture data, EGFP-Hec1 expression has been found to strongly inhibit tumor growth in a mouse xenograft model by disrupting mitosis and inducing multipolar spindles. The results of these experiments have been collected in a paper published in 2015 (Orticello et al. N-Terminus modified Hec1 suppresses tumour growth by interfering with kinetochore-microtubule dynamics. Oncogene, 34: 3325-3335).
For my Master degree in Genetics and Molecular Biology, I joined the Neuroepigenetic Lab of Andrea Fuso Ph.D. in the Department of Experimental Medicine at “La Sapienza” University in Rome, Italy. I have been working on the epigenetic alterations in the Alzheimer’s disease using mouse models and in particular, I have focused the investigation on the methylation pattern of some genes that are very well-known in this neurodegenerative disease. I have also been partially involved in a project on the differential expression of miRNAs in Alzheimer’s disease ( Fuso A. et al., The complex interplay between DNA methylation and miRNAs in gene expression regulation. Biochimie 2020).
I joined the STEMD laboratory in October 2022 as a Visiting Student for a three months project. Under the supervision of Veronica Astro, we will focus on culture maintenance and differentiation of iPSCs derived from Klinefelter Syndrome patients into neural stem cells up to the generation of neurons and 3D brain organoids
Biological and Environmental Science and Engineering Division (BESE)