Mechanisms of non-oncogene addiction in cancer
Alessandra Agresti
Email: agresti.alessandra@hsr.it
Location: DIBIT2, 4A2, Room 44
Research Associate, Mechanisms of non-oncogene addiction in cancer
BRIEF INTRODUCTION
In my career, I have always been interested in chromatin structure and dynamics and I have been involved in and coordinated studies on chromatin, repetitive DNA, transcription, TFs, cancer, inflammation, envelopathies and dynamic gene regulatory processes in living cells.
In what I consider the best achievement in my career, I demonstrated that modulation of nucleosome numbers is a novel layer of epigenetic regulation actively controlled in primary and cancer cells to respond to environmental cues like aging, cancer and inflammation.
As further achievements, I showed for the first time that the transient immobilization of TFs generates a window of opportunity for the enhanceosome to nucleate transcription complexes. Thus, an enhanceosome can be considered a hyperdynamic rheostat able to sense the environment and to get activated only when well-defined sets of molecular species are available.
By using microscopy technologies like FRET and FRAP in living cells, I have contributed to quantify the fast protein-protein interactions of TFs like Glucocorticoid Receptor, p65/NF-kB, histones and HMGB1 on actively transcribed promoters in living cells.
Building on these results, I then demonstrated that NF-kB behaves as a damped oscillator able to synchronize to periodic external perturbations with no memory of the past. This work suggested that NF-κB oscillatory dynamics are a means of segmenting time to provide opportunity windows for the cell to make decisions and respond to the environment.
Recently, I’ve characterised NF-κB activation in plasmacells in the BM of Multiple Myeloma patients. We showed that activation is mild, restricted to a minority of cells and modulated by the interplay of restraining physical microenvironmental cues and activating IL-1β-dependent stroma-to-MM crosstalk.
RESEARCH ACTIVITY
At present, I’m interested in the role of the Promyelocytic Leukemia Protein (PML) in modulating chromatin structure and transcription in in vitro models of Clear-cell Renal Carcinoma.
1984 M.Sc. in Biological Sciences, University of Milan, Italy
2020/2021 Professor, “Genetics and developmental biology” (BIO 11), Università Vita-Salute San Raffaele, Milan, Italy
2018-2023 Abilitazione Scientifica Nazionale 05/E2 BIOLOGIA MOLECOLARE - FASCIA: I; Abilitazione Scientifica Nazionale 05/F1 BIOLOGIA APPLICATA- FASCIA: I Ministero dell'Istruzione dell'Università e della Ricerca Scientifica
2024-present Senior researcher @ “Mechanisms of non-oncogene addiction in cancer Unit”
2022-2024 Senior researcher @ “Lymphocyte activation Unit” first
2009-2022 Group Leader, “In vivo chromatin and transcription”
2000-2009 Staff Scientist, “Chromatin Dynamics Unit”
1993-2000 Researcher, S. Raffaele Scientific Institute, Milan, Italy