Testa Group
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, as 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.
Group members
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Giuseppe Testa
Head of Neurogenomics Research Centre -
Matteo Bonfanti
Bioinformatics Technician -
Nicolò Caporale
Scientific Advisor -
Davide Castaldi
PhD student -
Lorenza Culotta
Senior technician -
Francesco Dossena
Internship Student -
Francesco Elli
Internship Student -
Veronica Finazzi
Internship Student -
Mathias Johansson
PhD student -
Martina Pezzali
PhD student -
Alejandro Lopez Tobon
Scientific Advisor -
Flavia Troglio
Scientific Advisor -
Alessia Valenti
Internship Student -
Emanuele Villa
Staff Scientist
Publications
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07/2021 - Taylor & Francis
Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders
Macroautophagy (hereafter referred to as autophagy) is a finely tuned process of programmed degradation and recycling of proteins and cellular components, which is crucial in neuronal function and synaptic integrity. Mounting evidence implicates chromatin remodeling in fine-tuning autophagy pathways. However, this epigenetic regulation is poorly understood in neurons. Here, we investigate the role in autophagy […]
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07/2021 - Wiley
Exploiting epigenetic dependencies in ovarian cancer therapy
Ovarian cancer therapy has remained fundamentally unchanged for 50 years, with surgery and chemotherapy still the frontline treatments. Typically asymptomatic until advanced stages, ovarian cancer is known as “the silent killer.” Consequently, it has one of the worst 5-year survival rates, as low as 30%. The most frequent driver mutations are found in well-defined tumor suppressors, […]
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05/2021 - Big Data & Society
Big Tech platforms in health research: Re-purposing big data governance in light of the General Data Protection Regulation’s research exemption
The emergence of a global industry of digital health platforms operated by Big Tech corporations, and its growing entanglements with academic and pharmaceutical research networks, raise pressing questions on the capacity of current data governance models, regulatory and legal frameworks to safeguard the sustainability of the health research ecosystem. In this article, we direct our […]
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12/2020 - The EMBO Journal
COVID-19 lessons from the dish: Dissecting CNS manifestations through brain organoids
COVID-19 is increasingly understood as a systemic disease with pathogenic manifestations beyond the respiratory tract. Recent work by Ramani et al (2020) dissects the cellular and molecular mechanisms of SARS-CoV-2’s neurotrophic properties, using viral exposure of human brain organoids. Their findings highlight neurons as primary target of cerebral SARS-CoV-2 infection and uncover its Tau-related neurotoxicity.
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11/2020 - Molecular Autism
High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons
Background Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26–28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational opportunities, because the hemideletion of […]
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