Prof. Raffaella Di Micco

Group Leader at the Telethon Institute for Gene Therapy, San Raffaele Hospital

The molecular mechanisms of stress responses in stem cells and during cancer progression have always been my main area of interest and fascination. Over the past 15 years I have worked on several different aspects of this incredibly broad field. During my PhD training I investigated the molecular mechanisms by which activated oncogenes induce DNA damage and cellular senescence. I was able to demonstrate that uncontrolled hyper-proliferation of oncogene expressing cells ultimately leads to DNA breaks and the activation of senescence as a tumor suppressor mechanism (Di Micco et al. Nature 2006). After graduation, I focused on the study of alterations of chromatin structure during senescence and discovered that heterochromatin formation induced by oncogenes is the consequence of DNA replication stress in the cells. I studied how alterations in chromatin could lead to new targeted therapies aimed to re-establish normal epigenetic patterns in cancer settings (Di Micco et al., Nat Cell Biol 2011; Sulli et al., Nature Rev Cancer 2012). In 2010, I moved to United States for a postdoctoral training in the laboratory of Dr. Eva Hernando at NYU School of Medicine to perform research aimed at understanding the epigenetic and transcriptional regulation in stem cell and during cancer development (Di Micco et al., 2014). In the first year of my postdoctoral training I was awarded with a prestigious European Molecular Biology Organization (EMBO) fellowship and in the second year I received a postdoctoral fellowship from Human Frontier Science Project (HFSP) and a New York Stem Cell Foundation (NYSCF) Druckenmiller postdoctoral fellowship. The postdoctoral experience in US made me a stronger and motivated scientist and contributed to prepare myself for a career as an independent investigator. Seeking for a group leader position, I decided to establish my research team at the San Raffaele-Telethon Institute for Gene Therapy (SR-TIGET) within the San Raffaele Hospital, in Milan in early 2016. The research in my lab capitalizes on the scientific expertise of my PhD and postdoctoral trainings in DNA damage, senescence, epigenetics and cancer and involves, as a model system, the human hematopoietic stem and progenitor cells (HSPCs). The main goal of my lab is to

dissect the interplay between chromatin and DNA damage upon stress in normal stem cells and in the context of malignant hematopoiesis with the final aim to develop hypothesis-driven strategies for therapeutic applications. I envision a research career that is pioneering and translational. Our laboratory perfectly integrates within a multidisciplinary team of basic biologists, statisticians, hematologists, clinicians with different yet complementary sets of expertise and takes advantage of relevant human patient samples. Our institute is an internationally recognized research center in the field of normal and malignant hematopoiesis and provided me a fully equipped and renovated lab space, state-of-art technologies and cutting-edge support facilities and infrastructures to promote scientific excellence and innovation.

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