Project acronym DENOVOSTEM
Project DE NOVO GENERATION OF SOMATIC STEM CELLS: REGULATION AND MECHANISMS OF CELL PLASTICITY
Researcher (PI) Stefano Piccolo
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Call Details Advanced Grant (AdG), LS4, ERC-2014-ADG
Summary The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues.
In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues.
For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ.
In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation.
Summary
The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues.
In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues.
For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ.
In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation.
Max ERC Funding
2 498 934 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym EUROCORR
Project The European correspondence to Jacob Burckhardt
Researcher (PI) Maurizio Ghelardi
Host Institution (HI) SCUOLA NORMALE SUPERIORE
Call Details Advanced Grant (AdG), SH5, ERC-2009-AdG
Summary The aim of this project is to map and publish in a critical edition the extensive correspondence of European intellectuals with the Swiss cultural historian Jacob Burckhardt over a period of more than half a century, from 1842 to 1897. This correspondence documents a crucial period in European history and culture, one which witnessed the emergence of art history as a separate discipline; serious political conflict in France, Germany, Italy and Switzerland; the birth of the nation-states of Italy and Germany; debate on the meaning and consequences of democracy as a system of government; and the rise of Caesarism in France. The effects of modernism are also discussed in this correspondence, from the culture of museums, art exhibitions and the first universal expositions (e.g., the Expositions Universelles in Paris) to the clash between industrial culture and neo-humanist ideals of education. The large body of correspondence received by Jacob Burckhardt (about two thousand letters conserved in various libraries and private archives) provides a cultural map of this crucial phase in the development of a new European identity.
Summary
The aim of this project is to map and publish in a critical edition the extensive correspondence of European intellectuals with the Swiss cultural historian Jacob Burckhardt over a period of more than half a century, from 1842 to 1897. This correspondence documents a crucial period in European history and culture, one which witnessed the emergence of art history as a separate discipline; serious political conflict in France, Germany, Italy and Switzerland; the birth of the nation-states of Italy and Germany; debate on the meaning and consequences of democracy as a system of government; and the rise of Caesarism in France. The effects of modernism are also discussed in this correspondence, from the culture of museums, art exhibitions and the first universal expositions (e.g., the Expositions Universelles in Paris) to the clash between industrial culture and neo-humanist ideals of education. The large body of correspondence received by Jacob Burckhardt (about two thousand letters conserved in various libraries and private archives) provides a cultural map of this crucial phase in the development of a new European identity.
Max ERC Funding
1 215 600 €
Duration
Start date: 2010-06-01, End date: 2015-05-31
Project acronym GREEK INTO ARABIC
Project Greek into Arabic: Philosophical Concepts and Linguistic Bridges
Researcher (PI) Cristina D'ancona
Host Institution (HI) UNIVERSITA DI PISA
Call Details Advanced Grant (AdG), SH5, ERC-2009-AdG
Summary One of the prominent features of Medieval Aristotelianism, both Arabic and Latin, is the fact that Aristotle has been credited with writings that, albeit Neoplatonic in origin, circulated under his name. Crucial as it might be for the genesis of Arabic-Islamic philosophy, the main text of the Neoplatonic tradition into Arabic, i.e., the so-called Theology of Aristotle, is still poorly edited and no running commentary exists on it. The Theology of Aristotle, derived in reality from Plotinus' Enneads, will be critically edited, translated and commented upon. This project will also study the Graeco-Arabic translations from a linguistic viewpoint. It will develop the extant Greek and Arabic Lexicon; of the Medieval translations of philosophical works into a computational resource. For the first time, the project allows Ancient and Arabic philosophy to interact with computational linguistics.
Summary
One of the prominent features of Medieval Aristotelianism, both Arabic and Latin, is the fact that Aristotle has been credited with writings that, albeit Neoplatonic in origin, circulated under his name. Crucial as it might be for the genesis of Arabic-Islamic philosophy, the main text of the Neoplatonic tradition into Arabic, i.e., the so-called Theology of Aristotle, is still poorly edited and no running commentary exists on it. The Theology of Aristotle, derived in reality from Plotinus' Enneads, will be critically edited, translated and commented upon. This project will also study the Graeco-Arabic translations from a linguistic viewpoint. It will develop the extant Greek and Arabic Lexicon; of the Medieval translations of philosophical works into a computational resource. For the first time, the project allows Ancient and Arabic philosophy to interact with computational linguistics.
Max ERC Funding
2 106 381 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
