Pediatric Hematology, Oncology and Hematopoietic Cell&Gene Therapy Area

High-Throughput Drug Screening for Precision Oncology

Dr. Elena Mariotto

Junior Principal Investigator

Research Activity

The High-Throughput Drug Screening for Precision Oncology unit is devoted to two major on-going projects listed below.

Establishing more representative in vitro 3D model to study cancer cell adaptation to the hostile tumor microenvironment (e.g. hypoxia, starvation, acidosis) in Glioma and Medulloblastoma pediatric brain tumor to unveil new targetable metabolic vulnerabilities (funded by Supporting TAlent in ReSearch Starting Grant, University of Padova, 2022-2024).

Drug Sensitivity Profiling (DSP) as promising tool to predict the response to chemotherapy in oncological pediatric patients in order to i) achieve effective therapeutic strategies for relapsed/refractory patients lacking actionable genetic alterations, ii) avoid unnecessary toxicity, and iii) prevent drug resistance and tumor relapse (funded by IRP-Starting Grant, Pediatric Research Institute, 2024-2027).
The High-Throughput Screening (HTS) facility consist of a semi-automated liquid handling platform (Microlab STAR 96-CORE, Hamilton), dedicated CO2 incubator and 1.5% O2 hypoxic cabinet (H35 Hypoxystation, Don Whitley Scientific), and a multimodal plate reader (Spark, Tecan). The facility enables to perform large drug repositioning/repurposing screening with in-house drug libraries (>3500 compounds) for anticancer drug discovery, dose-response sensitivity profiling and complex drug synergism studies to accelerate the identification and validation of new treatment options for pediatric cancers.
In collaboration with Prof. Giampietro Viola, I have been actively involved in the study of Bcl2-Associated AthanoGene (BAG) protein family in sustaining tumor relapse and chemotherapy resistance in pediatric tumors. Thanks to this project, we successfully designed a novel BAG3 inhibitor able to sensitize cancer cell to chemotherapy (in partnership with Evotec pharmaceutical company, Aptuit Srl, Verona, Italy).

Team Members

Dr. Elena Mariotto – Junior Principal Investigator
Dr. Chiara Marchioro – PhD Student
Dr. Martina Canton – PhD Student
Dr. Martina Portaluri – Undergraduate fellow

Selected Publications

• Mariotto E, Rampazzo E, Bortolozzi R, Rruga F, Zeni I, Manfreda L, Marchioro C, Canton M, Cani A, Magni R, Luchini A, Bresolin S, Viola G, and Persano L. Molecular and functional profiling of chemotolerant cells unveils nucleoside metabolism-dependent vulnerabilities in medulloblastoma. Acta Neuropathol Commun, 11 (2023) 183. https://doi.org/10.1186/s40478-023-01679-7
• Budassi F, Marchioro C, Canton M, Favaro A, Sturlese M, Urbinati C, Rusnati M, Romagnoli R, Viola G, and Mariotto E. Design, synthesis and biological evaluation of novel 2,4-thiazolidinedione derivatives able to target the human BAG3 protein. Eur J Med Chem, 261 (2023) 115824. https://doi.org/10.1016/j.ejmech.2023.115824
• Mariotto E, Corallo D, Pantile M, Giarin E, Pigazzi M, Basso G, Viola G, Aveic S. BAG1 down-regulation increases chemo-sensitivity of acute lymphoblastic leukaemia cells. J Cell Mol Med. 2021;25(18):9060-5. https://doi.org/10.1111/jcmm.16822
• Mariotto E, Viola G, Zanon C, Aveic S. A BAG’s life: Every connection matters in cancer. Pharmacology & Therapeutics, 107498 (2020). https://doi.org/10.1016/j.pharmthera.2020.107498
• Mariotto E, Bortolozzi R, Volpin I, Carta D, Serafin V, Accordi B, Basso G, Navarro PL, Lopez-Cara LC, Viola, G. EB-3D a novel choline kinase inhibitor induces deregulation of the AMPK-mTOR pathway and apoptosis in leukemia T-cells. Biochem Pharmacol. 2018 Sep;155:213-223. https://doi.org/10.1016/j.bcp.2018.07.004