Team members
Irene Taddei
Nicolas Pons
Signalling networks for stemness and tumorigenesis
Our team studies resilience versus vulnerability of cells to signalling fluctuations to understand how cancer starts, evolves, and responds to treatments.
Our team studies resilience versus vulnerability of cells to signalling fluctuations to understand how cancer starts, evolves, and responds to treatments. A key tool in our studies is a unique mouse genetic setting in which slightly increased wild-type receptor tyrosine kinase levels trigger the tumorigenic program in vulnerable tissues: liver and mammary gland. This “inside-out” genetic setting is a predisposing cancer model open to a variety of spontaneous alterations, thoroughly recapitulating disease features occurring in human patients. By combining complementary tools within interdisciplinary approaches, we identify new mechanisms at the root of tissue homeostasis destabilisation, tumour initiation, progression, as well as vulnerabilities to exploit for targeted therapies. Furthermore, we study how qualitative and quantitative signalling changes lead to diversified cell behaviours using stem cell cultures, organoids, and tumoroids, to document how perception of environmental signals and modulation of epithelial integrity impact cell behaviour, cell-cell interaction, and the acquisition of diversified cell identities.
Publications
Epithelial disruption drives mesendoderm differentiation in human pluripotent stem cells by enabling TGF-β protein sensing
MYC and MET cooperatively drive hepatocellular carcinoma with distinct molecular traits and vulnerabilities
BCL-XL blockage in TNBC models confers vulnerability to inhibition of specific cell cycle regulators
ADAMTSL5 is an epigenetically activated gene that confers tumorigenic properties and drug resistance in hepatocellular carcinoma
Modeling Heterogeneity of Triple-Negative Breast Cancer Uncovers a Novel Combinatorial Treatment Overcoming Primary Drug Resistance
Tracking dynamics of spontaneous tumours in mice using Photon Counting Computed Tomography
Epithelial disruption drives mesendoderm differentiation in human pluripotent stem cells by enabling TGF-β protein sensing
MYC and MET cooperatively drive hepatocellular carcinoma with distinct molecular traits and vulnerabilities
BCL-XL blockage in TNBC models confers vulnerability to inhibition of specific cell cycle regulators
ADAMTSL5 is an epigenetically activated gene that confers tumorigenic properties and drug resistance in hepatocellular carcinoma
Enhanced differentiation of human induced pluripotent stem cells toward the midbrain dopaminergic neuron lineage through GLYPICAN-4 downregulation
Modeling Heterogeneity of Triple-Negative Breast Cancer Uncovers a Novel Combinatorial Treatment Overcoming Primary Drug Resistance
Tracking dynamics of spontaneous tumours in mice using Photon Counting Computed Tomography
Tracking Dynamics of Spontaneous Tumors in Mice Using Photon-Counting Computed Tomography
Evaluating the landscape of gene cooperativity with RTKs in liver tumorigenesis
Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis
Hypermethylation of gene body CpG islands predicts high dosage of functional oncogenes in liver cancer
A Phosphokinome-based screen uncovers new drug synergies for cancer driven by liver-specific gain of non-oncogenic RTKs
Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells
Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.
Reducing Glypican-4 in ES Cells Improves Recovery in a Rat Model of Parkinson’s Disease by Increasing the Production of Dopaminergic Neurons and Decreasing Teratoma Formation.
Met signaling in cardiomyocytes is required for normal cardiac function in adult mice.
Strategies to Overcome Drug Resistance of Receptor Tyrosine Kinase-Addicted Cancer Cells.
Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy.
Met acts through Abl to regulate p53 transcriptional outcomes and cell survival in the developing liver.
Modulating Glypican4 suppresses tumorigenicity of embryonic stem cells while preserving self-renewal and pluripotency.
‘Click’ synthesis of a triazole-based inhibitor of Met functions in cancer cells.
Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures.
Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling.
MET signaling in GABAergic neuronal precursors of the medial ganglionic eminence restricts GDNF activity in cells that express GFRα1 and a new transmembrane receptor partner.
Pool-specific regulation of motor neuron survival by neurotrophic support.
Genetic analysis of specific and redundant roles for p38alpha and p38beta MAPKs during mouse development.
Hepatocyte growth factor protects retinal ganglion cells by increasing neuronal survival and axonal regeneration in vitro and in vivo.
Enhanced neuronal Met signalling levels in ALS mice delay disease onset.
Somitic origin of the medial border of the mammalian scapula and its homology to the avian scapula blade.
A new Met inhibitory-scaffold identified by a focused forward chemical biological screen.
Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis.
Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner.
Glypicans are differentially expressed during patterning and neurogenesis of early mouse brain.
Imino-tetrahydro-benzothiazole derivatives as p53 inhibitors: discovery of a highly potent in vivo inhibitor and its action mechanism.
Combined signaling through ERK, PI3K/AKT, and RAC1/p38 is required for met-triggered cortical neuron migration.
Mitogen-inducible gene 6 is an endogenous inhibitor of HGF/Met-induced cell migration and neurite growth.
Novel cyclized Pifithrin-alpha p53 inactivators: synthesis and biological studies.
A dual fate of the hindlimb muscle mass: cloacal/perineal musculature develops from leg muscle cells.
Proapoptotic function of the MET tyrosine kinase receptor through caspase cleavage.
Met signaling is required for recruitment of motor neurons to PEA3-positive motor pools.
Coupling Met to specific pathways results in distinct developmental outcomes.
News
How disruption drives change
Interaction between tight junction formation and gastrulation signals regulates mesendoderm differentiation in hiPSCs
A new genetic cooperation acting on liver cancer has been uncovered in patients and functionally documented in vivo
Through an international collaboration, using breast cancer as a biological paradigm, Flavio Maina Team publishes a work in the Theranostics journal exemplifying how specificity in targeting cell cycle regulators is essential for combinatorial cancer therapies.
The teams of F Maina and L Kerkerian-Le Goff publish in Stem Cells Translational Medicine a work led by Rosanna Dono showing that levels of the signal modulator GLYPICAN-4 are critical for the generation of midbrain dopamine neurons from human induced pluripotent stem cells and for overcoming their tumorigenic properties.
Maina Team publishes in Advanced Science the setup of a genetic system that models, in mice, the heterogeneity and primary resistance to treatment of human Triple Negative Breast Cancer (TNBC).
Maina Team publishes in Journal of Hepatology. The team found that ADAMTSL5 is an epigenetically activated oncogene overexpressed in a large fraction of human HCC patients and in HCC mouse models.
Researchers have used the CERN pixels to follow tumour evolution in a liver cancer mouse model.
The mission is to contribute to the team research on mechanistic and functional characterization of signalling circuits in cancer, develop novel therapeutic and diagnostic tools.
Team members
Alumni
Funding bodies
