Advancing Epigenetics Towards Systems Biology

Raffaella Di Micco

San Raffaele Telethon Institute for Gene Therapy, Milan, Italy

Chromatin and DNA damage response crosstalk in the hematopoietic system in aging and cancer

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raffaella di micco

Our research team is interested in dissecting the transcriptional and epigenetic mechanisms that regulate stem cell aging, differentiation and cancer in the hematopoietic system. In the hematopoietic stem cell compartment (HSPCs) aging results from the inability of HSPC to replenish short-lived cells and guarantee tissue homeostasis. The functional deterioration of the hematopoietic axis associates with a progressive reduction in immune response and an increased incidence of anemia and myelodisplastic disorders and hematopoietic malignancies in the elderly. Mutations in chromatin regulators have been found in HSPC from geriatric subjects suggesting that global changes in the epigenome may contribute to the aging phenotype and be exploited for therapeutic intervention. Combining cell and molecular biology approaches, together with next generation sequencing methods and clinically relevant human samples we are studying mechanisms governing the identity of aged cells and their progression towards malignancies. In these settings, we are dissecting the interplay between DNA damage response activation and chromatin biology