Our Vision
The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond.
This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place.
In the past, biological research has focused on questions that could be addressed by a reductionist program of genetics.
The organism (and its development) is currently considered an epiphenomenon of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism.
This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels.
Thus, by no means Systems Biology could be viewed a ‘simple’ ‘gradual’ extension of Molecular Biology.
Tumor Reversion
Phase transitions processes
The pathogenesis of several degenerative diseases, including cancer, mostly relies on a cell/tissue differentiation process ‘gone awry’.
A complex system is highly sensitive even to subtle changes in the surrounding milieu (the so-called morphogenetic field) when it enters near some critical points (the bifurcation points leading to metastable states, according to the Waddington’s landscape framework).
At these points, the system can experience a phase-transition, leading to different cell fate specification, upon the influence of different physical and molecular (namely toxicant, like nicotine) factors.
Thereby, it is of priceless value understanding the non-linear dynamics of such processes, to capture their architecture by means a proper mathematical modelling, and how to modify them through a pharmacological approach.
Namely, the natural polyol Inositol (and its phosphate derivatives) is investigated thoroughly, given that inositol showed to modulate epithelial-mesenchymal transition (EMT vs MET) by targeting the expression of several genes, the activation of the PI3K pathway, as well as the apoptotic process. By modulating EMT vs MET, Inositol can antagonize first steps of carcinogenesis while, by inhibiting apoptosis in normal cells it can easily counteract chemotherapy-induced effects on megakaryocytes. As inositol undergoes a complex metabolic transformation inside the cell, an in depth metabolomic study is currently ongoing to evaluate its metabolic fate.
Modulation of EMT is also at the core of the gene reprogramming that occur during tumor reversion. Tumor reversion induced by physical or molecular cues has been already reported.
We are investigating such processes by means of a model based on the therapeutic potential represented by protein extracts from embryo fish. Embryo fish extracts promote apoptosis and/or foster differentiation/reversion in different cancer types, both in vitro as well as in vivo.
Understanding how both inositol and embryo fish extract modulate phase transitions in cancer cells is therefore of critical relevance for translational medicine.
Developmental processes and theory of the organisms
Study of the developmental processes points primarily on early oocyte/embryo differentiating processes occurring during the early life stages.
We are investigating pathways involved in oocyte maturation (namely those involving steroidogenesis) by pointing out how changes in the overall cytoskeleton organization and in the oocyte/microenvironment cross talk can efficiently modulate oocyte maturation and further the implantation process.
To address these issues we are using a 3D-model – involving both the oocyte and an experimental reconstituted endometrium-like scaffold. The modulatory role of natural pharmacological compounds (like inositol, melatonin and α-lipoic acid) is under scrutiny to evaluate is such nutraceutical manipulation can improve the oocyte maturation process.
Furthermore, the potential utility of such compounds in treatment of infertility disorders (like Polycystic Ovary Syndrome) is currently under scrutiny.
Phenotypic Differentiation
Biophysical constraints
Phenotypic differentiation is underpinned by a complex molecular program, which involves both complex gene-regulatory circuits (behaving according to a non-linear dynamics) and molecular signaling.
However, these factors exert only a permissive role, while a more prominent effect is exercised by internal/external constraints (namely of physical origin), acting as instructive cues.
A paradigmatic example is provided by gravity, which showed to be instrumental in shaping cell differentiation in many experimental models.
We are investigating how microgravity and other physical cues may efficiently influence cell fate transitions in both normal and pathological conditions.
Moreover, as the effects of physical cues are mostly conveyed through the cytoskeleton (CSK) and the specialized cell-to-cell and cell-matrix adhesion structures, we are especially committed in investigating cytoskeleton and nucleoskeleton quantitative structure and dynamics.
To achieve a reliable systems biology representation of such complex processes, tailored, mathematical modelling approaches and high performance computing studies are usually developed.
Mariano
Bizzarri
Mariano Bizzarri PhD, M.D., is Associate Professor of Clinical Pathology in the Department of Experimental Medicine at University Sapienza, Rome (Italy).
Alessandra
Cucina
Alessandra Cucina PhD, is a researcher at the Laboratory of Experimental Research Castro Laurenziano of “Pietro Valdoni” Department of Surgery, “La Sapienza” University, Rome, Italy.
Alessandro
Giuliani
Alessandro Giuliani is involved since more than thirty years in the generation and testing of soft physical and statistical models for life sciences.
Sara
Proietti
Dr. Sara Proietti, is a post-doc researcher affiliated to the Department of Surgery P. Valdoni at the University La Sapienza of Rome.
Andrea
Fuso
Andrea Fuso, Ph.D., is guest researcher at Sapienza University of Rome, Department of Surgery “P. Valdoni”, and scientific consultant for Lo.Li.Pharma.
Andrea
Pensotti
Graduated in Pharmaceutical Chemistry at University of Milan in 2009, he finalized his studies with a professional master in management in London.
Rosaria A.
Cavallaro
Rosaria A. Cavallaro, PhD., is a Research Associate at Sapienza University of Rome, Department of Surgery “P. Valdoni”, Laboratory of experimental research “Castro Laurenziano”.
Maria Grazia
Masiello
Maria Grazia Masiello, PhD, is a Postdoctoral Researcher in the Department of Surgery “P. Valdoni” at University Sapienza, Rome (Italy).
Simona
Dinicola
Dr. Simona Dinicola, is a post-doc researcher affiliated to the Department of Experimental Medicine at the University La Sapienza of Rome.
Myselis
Santiago-Reyes
Myselis Santiago-Reyes earned her Master’s Degree in Genetics and Molecular Biology on December, 2017 at La Sapienza University in Rome, Italy.
Gianmarco
Fabrizi
Gianmarco Fabrizi, is a student of the Faculty of pharmacy and medicine, at the University La Sapienza of Rome.
Mirko
Minini
Ph.D. student Mirko Minini received a Master’s Degree from ‘La Sapienza’ University of Rome in Genetics and Molecular Biology cum laude.
Roberto Taramelli
Professor of Human GeneticsMy interests have been, from the beginning of my scientific career, within the field of human genetics.
Ana Soto
Professor in the Department of Integrative Physiology and PathobiologyAna Soto is a professor in the Department of Integrative Physiology and Pathobiology at Tufts University School of Medicine, in Boston, MA, and Membre Correspondent Etranger at the Centre Cavaillès, Ecole Normale Supérieure, Paris
Carlos Sonnenschein
Professor at Tufts University School of MedicineCarlos Sonnenschein is a Professor at Tufts University School of Medicine, a Corresponding Member at the Centre Cavaillès, Ecole Normale Supérieure (ENS), Paris, France, and a Fellow at the Institute of Advanced Studies-at-Nantes, France
Giuseppe Longo
Directeur de Recherche (DRE) CNRS at Centre Interdisciplinaire CavaillèsGiuseppe Longo is Directeur de Recherche (DRE) CNRS at Centre Interdisciplinaire Cavaillès, (République des Savoirs, Collège de France et l’Ecole Normale Supérieure, Paris).
Arturo Bevilacqua
Professore Ordinario di Biologia ApplicataProfessore Ordinario di Biologia Applicata (BIO/13), in servizio presso la Facoltà di Medicina e Psicologia dell’Università “Sapienza” di Roma.
Giulia Ricci
Aggregate ProfessorSince 2011 Dr. Giulia Ricci has been in charge as Tutor and as part of the faculty of the School of Doctorate in Morphogenesis and Tissue Engineering of the University of Rome “Sapienza”.
Chiara Simeoni
I have invested my competences for developing innovative teach ng projects in Mathematical Modelling for the Applied Sciences.
Corrado Mascia
Associate Professor Mathematics Department G.CastelnuovoCorrado Mascia is an Associate Professor at the Mathematics Department "G.Castelnuovo" Sapienza, University of Rome.
Roberto Verna
Professore Ordinario di Patologia ClinicaDirettore del Centro di Ricerca per la Medicina e il Management dello Sport della Sapienza Università di Roma.
Saleh H. Alwasel
Stefano Bellucci
Alfredo Colosimo
Giorgio Fanò
Fabrizio Frezza
Rodolfo Guzzi
Abdel Halim Harrath
Maria A. Mariggiò
Maurizio Nordio
Daniel Satgè
Stefano Serafini
Federico Venuta
Paolo Zamboni
The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond.
This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place.
In the past, biological research has focused on questions that could be addressed by a reductionist program of genetics.
The organism (and its development) is currently considered an epiphenomenon of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism.
This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels.
Thus, by no means Systems Biology could be viewed a ‘simple’ ‘gradual’ extension of Molecular Biology.
Tumor Reversion
Phase transitions processes
The pathogenesis of several degenerative diseases, including cancer, mostly relies on a cell/tissue differentiation process ‘gone awry’.
A complex system is highly sensitive even to subtle changes in the surrounding milieu (the so-called morphogenetic field) when it enters near some critical points (the bifurcation points leading to metastable states, according to the Waddington’s landscape framework).
At these points, the system can experience a phase-transition, leading to different cell fate specification, upon the influence of different physical and molecular (namely toxicant, like nicotine) factors.
Thereby, it is of priceless value understanding the non-linear dynamics of such processes, to capture their architecture by means a proper mathematical modelling, and how to modify them through a pharmacological approach.
Namely, the natural polyol Inositol (and its phosphate derivatives) is investigated thoroughly, given that inositol showed to modulate epithelial-mesenchymal transition (EMT vs MET) by targeting the expression of several genes, the activation of the PI3K pathway, as well as the apoptotic process. By modulating EMT vs MET, Inositol can antagonize first steps of carcinogenesis while, by inhibiting apoptosis in normal cells it can easily counteract chemotherapy-induced effects on megakaryocytes. As inositol undergoes a complex metabolic transformation inside the cell, an in depth metabolomic study is currently ongoing to evaluate its metabolic fate.
Modulation of EMT is also at the core of the gene reprogramming that occur during tumor reversion. Tumor reversion induced by physical or molecular cues has been already reported.
We are investigating such processes by means of a model based on the therapeutic potential represented by protein extracts from embryo fish. Embryo fish extracts promote apoptosis and/or foster differentiation/reversion in different cancer types, both in vitro as well as in vivo.
Understanding how both inositol and embryo fish extract modulate phase transitions in cancer cells is therefore of critical relevance for translational medicine.
Developmental processes and theory of the organisms
Study of the developmental processes points primarily on early oocyte/embryo differentiating processes occurring during the early life stages.
We are investigating pathways involved in oocyte maturation (namely those involving steroidogenesis) by pointing out how changes in the overall cytoskeleton organization and in the oocyte/microenvironment cross talk can efficiently modulate oocyte maturation and further the implantation process.
To address these issues we are using a 3D-model – involving both the oocyte and an experimental reconstituted endometrium-like scaffold. The modulatory role of natural pharmacological compounds (like inositol, melatonin and α-lipoic acid) is under scrutiny to evaluate is such nutraceutical manipulation can improve the oocyte maturation process.
Furthermore, the potential utility of such compounds in treatment of infertility disorders (like Polycystic Ovary Syndrome) is currently under scrutiny.
Phenotypic Differentiation
Biophysical constraints
Phenotypic differentiation is underpinned by a complex molecular program, which involves both complex gene-regulatory circuits (behaving according to a non-linear dynamics) and molecular signaling.
However, these factors exert only a permissive role, while a more prominent effect is exercised by internal/external constraints (namely of physical origin), acting as instructive cues.
A paradigmatic example is provided by gravity, which showed to be instrumental in shaping cell differentiation in many experimental models.
We are investigating how microgravity and other physical cues may efficiently influence cell fate transitions in both normal and pathological conditions.
Moreover, as the effects of physical cues are mostly conveyed through the cytoskeleton (CSK) and the specialized cell-to-cell and cell-matrix adhesion structures, we are especially committed in investigating cytoskeleton and nucleoskeleton quantitative structure and dynamics.
To achieve a reliable systems biology representation of such complex processes, tailored, mathematical modelling approaches and high performance computing studies are usually developed.
[tlpteam col=”4″ member=”12″ orderby=”menu_order” order=”ASC” layout=”1″]
Roberto Taramelli
Professor of Human GeneticsMy interests have been, from the beginning of my scientific career, within the field of human genetics.
Ana Soto
Professor in the Department of Integrative Physiology and PathobiologyAna Soto is a professor in the Department of Integrative Physiology and Pathobiology at Tufts University School of Medicine, in Boston, MA, and Membre Correspondent Etranger at the Centre Cavaillès, Ecole Normale Supérieure, Paris
Carlos Sonnenschein
Professor at Tufts University School of MedicineCarlos Sonnenschein is a Professor at Tufts University School of Medicine, a Corresponding Member at the Centre Cavaillès, Ecole Normale Supérieure (ENS), Paris, France, and a Fellow at the Institute of Advanced Studies-at-Nantes, France
Giuseppe Longo
Directeur de Recherche (DRE) CNRS at Centre Interdisciplinaire CavaillèsGiuseppe Longo is Directeur de Recherche (DRE) CNRS at Centre Interdisciplinaire Cavaillès, (République des Savoirs, Collège de France et l’Ecole Normale Supérieure, Paris).
Arturo Bevilacqua
Professore Ordinario di Biologia ApplicataProfessore Ordinario di Biologia Applicata (BIO/13), in servizio presso la Facoltà di Medicina e Psicologia dell’Università “Sapienza” di Roma.
Giulia Ricci
Aggregate ProfessorSince 2011 Dr. Giulia Ricci has been in charge as Tutor and as part of the faculty of the School of Doctorate in Morphogenesis and Tissue Engineering of the University of Rome “Sapienza”.
Chiara Simeoni
I have invested my competences for developing innovative teach ng projects in Mathematical Modelling for the Applied Sciences.
Corrado Mascia
Associate Professor Mathematics Department G.CastelnuovoCorrado Mascia is an Associate Professor at the Mathematics Department "G.Castelnuovo" Sapienza, University of Rome.
Roberto Verna
Professore Ordinario di Patologia ClinicaDirettore del Centro di Ricerca per la Medicina e il Management dello Sport della Sapienza Università di Roma.
Saleh H. Alwasel
Stefano Bellucci
Alfredo Colosimo
Giorgio Fanò
Fabrizio Frezza
Rodolfo Guzzi
Abdel Halim Harrath
Maria A. Mariggiò
Maurizio Nordio
Daniel Satgè
Stefano Serafini
Federico Venuta
Paolo Zamboni