2017 Recipient Beatrice Rondinelli, PhD

Beatrice Rondinelli, PhD

EZH2 Determines PARPi Resistance and Fork Stabilization in Ovarian Tumors

Project Summary

Epithelial ovarian cancers (EOCs) are late-diagnosed and lethal tumors. A high percentage of EOCs initially respond to current therapies but eventually develop resistance. This greatly reduces patient survival. We have a limited knowledge of how resistance to therapies is achieved by these tumors. Here, we identify a new mechanism of drug resistance in EOCs. We found that the protein EZH2 affects drug resistance. In this proposal, we aim to fully characterize how drug resistance is influenced by EZH2. Our work will allow us to predict whether a patient will respond well to therapies or develop resistance.

This research has been generously supported by Ovarian Cycle Newport, RI, in memory of Marilyn Bonner Feingold.

Areas of Research:

Bio

My name is Beatrice Rondinelli, I come from Italy and I am currently a postdoctoral fellow in Dr. Alan D. D’Andrea’s lab at Dana Farber Cancer Institute in Boston, MA, United States. After a Bachelor at University of Bologna and a Master in Biotechnology at the San Raffaele University in Milan, Italy, I graduated from Dr. Giovanni Tonon’s laboratory, where I conducted functional genomics studies on previously uncharacterized tumor suppressor genes in sporadic renal cancer. During my graduate studies, we identified the histone demethylase KDM5C as a master regulator of heterochromatin maintenance. We demonstrated that rampant genomic instability ensues when KDM5C undergoes inactivating mutations in cancer cells. Importantly, sporadic cancer patients presenting with mutated KDM5C also show a poorer prognosis. A Banca del Monte di Lombardia Award in 2014 and an Italian Association for Cancer Research (AIRC/FIRC) Fellowship for Abroad in 2015 gave me the possibility to join Dr Alan D. D’Andrea’s team in Boston with the ultimate goal of better understanding how cancer cells survive to high levels of DNA damage and to uncover new dependencies that might be exploited to eradicate these cells. As a postdoctoral fellow in Dr D’Andrea’s lab, I will bridge my specific experience in cancer epigenetics with Dr D’Andrea’s extensive knowledge in DNA repair. My goal is to better elucidate which role chromatin modifiers have in the tumorigenesis and in the chemosensitivity of homologous recombination-deficient (HR-deficient) ovarian cancers. Indeed, our knowledge on this topic is still limited.