PROJECT
SUPERVISORS

Project Supervisor

Valerio Orlando

Background

Prof. Valerio Orlando obtained his PhD in Molecular Biology at University La Sapienza in Rome Italy Pasteur-Cenci Bolognetti Foundation award Best Thesis in Molecular Biology 1989), then carried on for postdoc at ZMBH Uni-Heidelberg (1991- 1997) in Renato Paro’s lab, where he contributed to develop the Chromatin Immunoprecipitation (ChIP) technology  (Orlando and Paro Cell 1993, Orlando 2000). He started his independent career in 1998 at San Raffaele Institute in Milan (Italy) where he established the Laboratory of Epigenetics and Genome reprogramming. In 2002 he joined Telethon Foundation, for which he moved to Naples to IGB CNR new Campus (2002-2008) where he was founder member of the Dulbecco Telethon Institute (DTI), and later in Rome at Santa Lucia Foundation (2008-2013). He has been a proactive member of Eu-funded Network of Excellence of Epigenetics (Epigenome and Epigenesys Networks of Excellence) and promoted and co-directed the First National Italy’s Flagship Project on Epigenetics (30M Euros/5y www.epigen.it).

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In 2013 he moved to KAUST where he founded the KAUST Environmental Epigenetics program. His entire career has been characterized by the curiosity for unsolved, novel  cutting edge questions, providing first evidence for relevant important aspects of epigenetic gene regulation including the intersection between Chromatin and Basal Transcription machinery (Breiling et al, Nature 2001, Orlando Cell 2003), Condensins and chromatin mediated epigenetic silencing (Breiling et al, Mol Cell 2001), 3D organization of Homeotic gene epigenetic memory (Lanzuolo et al Nat Cell Biol 2007), first evidence and mechanistic role of RNAi components in animal cell nuclei (Cernilogar et al, Nature 2011). 

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Research

Prof. Orlando’s interest is the exploration of the epigenetic mechanisms of adaptation and howar, Prof. Orlando's lab investigates the chromatin and nuclear architecture mediated mechanisms that control and maintain cell identity and plasticity and in particular the contribution of the noncoding part of the genome and associated protein complex regulators. These include the “cell memory” chromosomal proteins called Polycomb and trithorax group and other chromatin structure regulators; (ii) the role of ncRNAs in epigenetic regulation and how this relates to development and adaptation, in particular in stress conditions (iii) the circadian clock and organ  to organ communication.

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Furthermore, as part of the investigation of the plastic properties of the genome in response to developmental and environmental cues, Prof. Orlando's lab new endeavor has been the exploration of the functional role of the repetitive part of the mammalian genome (50% of total DNA content), in particular Retrotransposons both in healthy and disease contexts. A major focus is AGING and RNA based potential therapeutic intervention for tissue homeostasis and regeneration to improve health span and prevent aging related pathological contexts.

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Publications

Bodega B, Marasca F, Ranzani V, Cherubini A, Della Valle F, Neguembor MV, Wassef M, Zippo A Lanzuolo C, Pagani M, Orlando V. Acytosolic Ezh1 isoform modulates a PRC2---Ezh1 epigenetic adaptive response in postmitotic cells. Nature Struct Mol Biol. 2017 May;24(5):444

Shuaib M, Parsi KM, Thimma M, Adroub SA, Kawaji H, Seridi L, Ghosheh Y, Fort A, Fallatah B, Ravasi T, Carninci P, Orlando V. (2019) Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells. Cell Systems. 9(5):446-45

Della Valle F, Thimma M, Caiazzo M, Pulcrano, Celii,M, Adroub S, Liu P, Lobato G, Broccoli V, Orlando V. (2020). Transdifferentiationof Mouse Embryonic Fibroblasts into Dopaminergic Neurons reactivates LINE-1 repetitive elements. Stem Cell Reports (Jan 14;14(1):60- 74

Bonetti A, et al, Gimenez J, et al…Orlando V* and Carninci P*, 2020 (RADICL-seq identifies general and cell type–specific principles of genome-wide RNA-chromatin interactions. Nature Communications Feb 24;11(1):1018 (* Co- corresponding authors)

Fallatah B, Shuaib M, Adroub S, Paytuv-Gallart A, Della Valle F, Nadeef S, Lanzuolo C, Orlando V. (2021). Ago1 controls myogenic differentiation by regulating eRNA mediated CBP guided epigenome reprogramming. Cell Reports 30;37(9):11006