|Unit:||Department of Surgical and Oncological Sciences|
|Section:||Cellular and Molecular Oncology Laboratory|
Dr. Veschi received her M.D. cum laude from “La Sapienza” University of Rome, Italy in 2006 and completed her Specialization in Oncology in 2011. Given her deeper interest for a more basic approach in research, she began her very productive Ph.D. training in Molecular Medicine in 2011 with Prof. Giuseppe Giannini in the Laboratory of Molecular Oncology at the “La Sapienza” University in Rome, headed by Prof. Alberto Gulino. Her studies focused on the role of MYCN in sensitizing neuroblastoma cells to DNA damage.
In particular, her contributions have clarified the role of Galectin-3 as a regulator of apoptosis and differentiation in Neuroblastoma (NB), defining it as a relevant prognostic marker. She contributed significantly to the understanding of the MYCN-dependent regulation of apoptosis by induction of the p53 (S46) kinase HIPK2 through a DNA-damage response in NB. She identified essential pathogenic mechanisms underlying the molecular axis HIPK2-p53-Galectin3 and well documented that this axis can be activated by the non genotoxic p53-reactivating compound Nutlin-3, suggesting that this pathway can be target of the tailored p53 reactivating therapy in patients with high-risk NB.
In 2013, Dr. Veschi journeyed to the Pediatric Oncology Branch of the National Institutes of Health (NIH), to complete her Ph.D. studies as part of the NIH Graduate Partners Program in the Cell and Molecular Biology Section laboratory of Dr. Carol J. Thiele at NCI and under the supervision of Dr. Ettore Appella, Chief of Chemical Immunology Section, Laboratory of Cell Biology, for her p53 studies.
During her 4 years experience at National Institutes of Health (NIH), Bethesda, Maryland, USA, she interrogated systematically the epigenetic landscape of NB cells by developing a high-throughput chromatin-focused small interfering RNA screening. She uncovered 16 epigenetic regulators critical for both the uncontrolled proliferation and the differentiation block in high-risk NBs. By performing both genetic and chemical screens, she identified SETD8, the H4K20me1 methyltransferase, as crucial in the proliferation and differentiation of NB cells.
She has brought to light a novel mechanism of inactivation of p53, providing a translational basis for innovative cancer therapies in NB tumors with p53 WT but functionally inactivated. Specifically, SETD8 inhibition rescues the pro-apoptotic and growth-arrest p53 functions by decreasing p53K382me1 and through the activation of the p53 canonical pathway.
These results had a significant and promising impact on cancer research as they were well recognized by the scientific community, published on a high-impact factor journal Cancer Cell and highlighted on Cancer Discovery journal, on Oncoscience Editorial and in the CCR Milestones Highlights as one of the top advances at the Center for Cancer Research for 2017. Dr. Veschi was appointed recipient of four significant awards for this innovative and clinically relevant results.
In 2016, Dr. Veschi joined the Laboratory of Cellular and Molecular Oncology, headed by Prof. Giorgio Stassi, at the Palermo University, where she is currently working as a Postdoctoral Fellow. Moreover, Dr. Veschi is still collaborating with the NIH as Special Volunteer. Her studies are now focusing on the role of p53 and its post translational modifications in cancer stem cells of adult cancers.