The Testa Group harnesses the unprecedented potential of cell reprogramming to study the molecular basis of human neuropsychiatric and neurological diseases (NPD), by chasing the dynamics of their unfolding in physio pathologically relevant models and straddling multiple scales of analysis from single cell resolution to organismal function.
One of the most tangible outputs of somatic cell reprogramming has been a paradigm shift in our ability to model human diseases, for which fundamental limitations have been so far: i) the scarce availability of primary diseased tissues, which is particularly salient for disorders of the nervous system; and ii) the difficulty of reconstructing developmental and patient-specific trajectories during the unfolding of diseases.
We are thus pursuing NPD modelling with human induced pluripotent stem cells (iPSC) coupled with the differentiation into relevant lineages through a range of complementary experimental paradigms, including glutamatergic neurons by induced expression of neurogenin-2 (NGN2), neural crest stem cells and 3-dimensional brain organoids that recapitulate salient stages of early brain development, including the diversity of cell populations unique to the human brain. This is allowing us to dissect the genetic and environmental components of NPD pathogenesis, by means of several "omics" approaches at a bulk and single cell resolution integrated with high throughput imaging and functional in vitro and in vivo assays.
The Testa Group focuses on a uniquely informative range of syndromes featuring intellectual disability and autism spectrum disorder that are caused by mutations or dosage alterations in epigenetic regulators and transcription factors, including Williams-Beuren Syndrome and 7q11.23 microduplication Syndrome, Kabuki Syndrome, ADNP-related autistic spectrum disorders, Weaver Syndrome, Gabriele-Testa-DeVries Syndrome, we well as on paradigmatic environmental factors that adversely impact on neurodevelopment, namely endocrine disruptive chemicals.
Finally, the prism of human neurodevelopmental disorders is also allowing us to investigate the logic of the gene regulatory networks underlying the evolution of the modern human face and brain, integrating the analysis of craniofacial dysmorphologies and brain alterations to illuminate the evolutionary-developmental trajectories underlying the modern human condition
Testa Group Publications
Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology
Cristina Cheroni, Nicolò Caporale & Giuseppe Testa
2020 - Molecular Autism
Thinking “ethical” when designing an international, cross‐disciplinary biomedical research consortium
Maria‐Elena Torres‐Padilla, Annelien L Bredenoord, Karin R Jongsma, Astrid Lunkes, Luca Marelli, Ines Pinheiro, Giuseppe Testa
2020 - The EMBO Journal
LifeTime and improving European healthcare through cell-based interceptive medicine
Nikolaus Rajewsky, Geneviève Almouzni, Stanislaw A. Gorski, Stein Aerts, Ido Amit, Michela G. Bertero, Christoph Bock, Annelien L. Bredenoord, Giacomo Cavalli, Susanna Chiocca, Hans Clevers, Bart De Strooper, Angelika Eggert, Jan Ellenberg, Xosé M. Fernández, Marek Figlerowicz, Susan M. Gasser, Norbert Hubner, Jørgen Kjems, Jürgen A. Knoblich, Grietje Krabbe, Peter Lichter, Sten Linnarsson, Jean-Christophe Marine, John Marioni, Marc A. Marti-Renom, Mihai G. Netea, Dörthe Nickel, Marcelo Nollmann, Halina R. Novak, Helen Parkinson, Stefano Piccolo, Inês Pinheiro, Ana Pombo, Christian Popp, Wolf Reik, Sergio Roman-Roman, Philip Rosenstiel, Joachim L. Schultze, Oliver Stegle, Amos Tanay, Giuseppe Testa, Dimitris Thanos, Fabian J. Theis, Maria-Elena Torres-Padilla, Alfonso Valencia, Céline Vallot, Alexander van Oudenaarden, Marie Vidal, Thierry Voet & LifeTime Community
2020 - Nature
The sociability spectrum: evidence from reciprocal genetic copy number variations
López-Tobón A, Trattaro S, Testa G.
2020 - Molecular Autism
Check the commentary on PsychologyToday.
Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD
Drakulic D, Djurovic S, Syed YA, Trattaro S, Caporale N, Falk A, Ofir R, Heine VM, Chawner SJRA, Rodriguez-Moreno A, van den Bree MBM, Testa G, Petrakis S, Harwood AJ.
2020 - Molecular Autism
KMT2B and Neuronal Transdifferentiation: Bridging Basic Chromatin Mechanisms to Disease Actionability
G. Barbagiovanni, M. Gabriele, G. Testa
2020 - Neurosci Insights
A small 7q11.23 microduplication involving GTF2I in a family with intellectual disability.
Pinelli M, Terrone G, Troglio F, Squeo GM, Cappuccio G, Imperati F, Pignataro P, Genesio R, Nitch L, Del Giudice E, Merla G, Testa G, Brunetti-Pierri N.
2020 - Clinical Genetics
DNA Methylation Signature for EZH2 Functionally Classifies Sequence Variants in Three PRC2 Complex Genes.
Choufani S, Gibson WT, Turinsky AL, Chung BHY, Wang T, Garg K, Vitriolo A, Cohen ASA, Cyrus S, Goodman S, Chater-Diehl E, Brzezinski J, Brudno M, Ming LH, White SM, Lynch SA, Clericuzio C, Temple IK, Flinter F, McConnell V, Cushing T, Bird LM, Splitt M, Kerr B, Scherer SW, Machado J, Imagawa E, Okamoto N, Matsumoto N, Testa G, Iascone M, Tenconi R, Caluseriu O, Mendoza-Londono R, Chitayat D, Cytrynbaum C, Tatton-Brown K, Weksberg R.
2020 - American Journal of Human Genetics
Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication.
Zanella M, Vitriolo A, Andirko A, Martins PT, Sturm S, O'Rourke T, Laugsch M, Malerba N, Skaros A, Trattaro S, Germain PL, Mihailovic M, Merla G, Rada-Iglesias A, Boeckx C, Testa G.
2019 - Science Advances