My research aims at studying the molecular switches acting as regenerative/cell-plasticity breaks by actively maintaining the cell fate, thereby ensuring the strict regulation of cell identity and/or numbers.
For example, by using genetic cell fate-tracing techniques, I studied a spontaneous age-dependent regeneration process in the mammalian pancreas, based on a cell-fate conversion. Although a natural attempt of mammalian regeneration, this regenerative mechanism was extremely inefficient, with only 2% of the cells converting at any given time point (Thorel et al., Nature, 2010; Chera et al. Nature, 2014). We investigated the cellular and molecular mechanisms behind this restricted cell identity change and revealed that Insulin and Hedgehog signalling pathways act as natural cell-plasticity breaks by actively maintaining cell-identity (Cigliola*, Ghila*, Thorel* et al., Nature Cell Biology, 2018; *equal contribution). These results are neither organ-specific nor isolated, with an incremental body of literature reporting cell-plasticity breaks in many mammalian tissue and organs. Several recent studies pointed towards a short list of signalling pathways involved, reviewed by us in Cigliola, Ghila et al., 2020, Stem Cells.
I am currently investigating the molecular mechanisms acting during cell reprogramming and differentiation using mouse models and hiPS-derived human cell models.
- (2022). Spatial Environment Affects HNF4A Mutation-Specific Proteome Signatures and Cellular Morphology in hiPSC-Derived β-Like Cells. Diabetes. 862-869.
- (2022). Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes. Scientific Reports.
- (2021). Chronically elevated exogenous glucose elicits antipodal effects on the proteome signature of differentiating human ipsc-derived pancreatic progenitors. International Journal of Molecular Sciences.
- (2021). A Method for Encapsulation and Transplantation into Diabetic Mice of Human Induced Pluripotent Stem Cells (hiPSC)-Derived Pancreatic Progenitors. Methods in molecular biology.
- (2020). In vivo environment swiftly restricts human pancreatic progenitors toward mono-hormonal identity via a HNF1A/HNF4A mechanism. Frontiers in Cell and Developmental Biology. 1-14.
- (2020). Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling . Scientific Reports. 1-16.
- (2020). Bioinformatic analyses of miRNA-mRNA signature during hiPSC differentiation towards insulin-producing cells upon HNF4α mutation. Biomedicines. 1-20.
- (2019). The effect of WnT pathway modulators on human iPSC-derived pancreatic beta cell maturation. Frontiers in Endocrinology. 1-13.
- (2019). Reprogrammed cells display distinct proteomic signaturesAssociated with colony morphology variability. Stem Cells International. 1-16.
- (2019). In vivo hyperglycemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress. Acta Physiologica. 1-16.
- (2019). Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling. bioRxiv - the preprint server for biology.
- (2019). Diabetes relief in mice by glucose-sensing insulin-secreting human α-cells. Nature. 43-48.
- (2018). Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon+ α-cells. Nature Cell Biology. 1267-1277.
- (2018). Novel protein signatures suggest progression to muscular invasiveness in bladder cancer. PLOS ONE. 1-15.
- (2017). Probing the missing mature β-cell proteomic landscape in differentiating patient iPSC-derived cells. Scientific Reports. 1-14.
- (2022). Editorial: Beta-Cell Fate: From Gene Circuits to Disease Mechanisms. Frontiers in Genetics.
- (2021). Islet transplantation tolerance in animals with defined histocompatibility and diabetes. bioRxiv - the preprint server for biology.
- (2021). 402.2: High Glucose Concentration Increases KATP Channel Activity but Suppresses Mitochondrial Respiration Ability in Insulin-producing Cells Regenerated From Stem Cells. Transplantation. S27-S27.
- (2021). Glucose during in vitro pancreatic beta cells regeneration: friends or for?
- (2019). Tissue repair brakes: A common paradigm in the biology of regeneration: Concise review. Stem Cells. 330-339.
2020-2023 Supportive therapy for diabetes by increasing the stress endurance and regenerative capacity of beta-cells (funded by EEA and Norway Grants funding scheme, RoNo2019)
2019-2020 Differentiating insulin-producing cells from induced pluripotent stem cells derived from diabetes patients (funded by Diabetesforbundet, PI)
2016-2019 Characterization of regulatory mechanisms in differentiating MODY-iPS-derived pancreatic cells (postdoctoral project funded by UiB, PI