San Raffaele Telethon Institute for Gene Therapy

Senescence in stem cell aging, differentiation and cancer


Group Leader

Raffaella Di Micco


Group research activity is interested in dissecting the mechanisms that regulate cellular senescence during aging, differentiation and cancer. Gene transcription, chromatin conformation and DNA damage orchestrate the tightly controlled program of cellular senescence. However, very little is known on how the identity of senescence cells is established and how it contributes to fundamental biological processes such as aging, cellular differentiation and cancer. By combining cell and molecular biology approaches, together with next generation sequencing and clinically relevant human samples, the unit is elucidating the functional role of senescence-associated pathways and regulators in the hematopoietic stem cell compartment (HSPCs).

Research activity

The aim is to identify molecular determinants of human aged and stressed hematopoiesis, focusing on both cell intrinsic and cell extrinsic mechanisms of stem cell aging. The group employs artificial nucleases to study the interplay between DNA damage response (DDR) and chromatin and senescence establishment in ex-vivo gene targeting strategies in HSPCs.
Therapy-induced senescence is a relatively unexplored area in hematological tumors because cancer cells often undergo a mixture of apoptosis and senescence following chemotherapy. In the lab, researchers are developing in vitro models of senescence induction upon DNA damaging agents and characterizing the functional role of therapy-induced senescent cells (TIS cells) on tumor survival and chemo-resistance.
As part of a collaborative project with the laboratory of Dr. Luca Vago, the unit is studying the transcriptional and epigenetic alterations responsible of leukemia immune evasion in paired AML patient samples. Thecomprehensive analysis involves DNA methylation studies, mapping of post-translational modifications on histone tails, a low input proteomic approach for modified histones and a functional screening platform to delay or revert cancer immuno-editing.