- E-mailluiza.ghila@uib.no
- Visitor AddressGlasblokkene 1Haukelandsbakken 155021 BergenRoom6114, 6th floor
- Postal AddressPostboks 78045020 Bergen
My research aims at studying the molecular switches acting as regenerative or cell-plasticity breaks by actively maintaining the cell fate, thereby ensuring the strict regulation of cell identity and/or numbers.
Currently, we are focusing on metabolic and immune players, which we recently identified to be involved in the emergence of the immediate neoplastic transformation signature in a model of bladder cancer. We intend to resolve the causal relationship and contribution to mechanisms regulating cell fate and tumour development by abolishing or augmenting their impact, with the final goal of aborting early neoplastic transformation.
Previously, 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.
- (2024). Targeted Gene Silencing by Using GapmeRs in Differentiating Human-Induced Pluripotent Stem Cells (hiPSC) Toward Pancreatic Progenitors. Methods in molecular biology. 23-38.
- (2024). Glucose Concentration in Regulating Induced Pluripotent Stem Cells Differentiation Toward Insulin-Producing Cells. Transplant International.
- (2023). Modulation of Unfolded Protein Response Restores Survival and Function of β-Cells Exposed to the Endocrine Disruptor Bisphenol A. International Journal of Molecular Sciences.
- (2023). Global proteomics reveals insulin abundance as a marker of human islet homeostasis alterations. Acta Physiologica. 15 pages.
- (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.
- (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.
- (2023). Hnf1a Is An Important Regulator in Ageing And Maturation Of Pancreatic Islets.
- (2023). Exploring the role of transcription factors HNF1A, HNF1B, and HNF4A in human pancreatic islet cell differentiation.
- (2023). Exploring the role of transcription factors HNF1A, HNF1B, and HNF4A in human induced pluripotent stem cell-derived pancreatic islet cell differentiation.
- (2022). Mapping tumour heterogeneity and predictive cancer signatures in vivo.
- (2022). Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors.
- (2023). Islet maturation and ageing is governed by the Hnf1a transcription factor.
- (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.
- (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.
- (2023). Mapping predictive bladder cancer signatures in a mouse model.
- (2023). Mapping islet architecture changes upon high fat diet challenge in a HNF1A-MODY mouse model.
- (2023). Investigating the developmental role of HNF1A, HNF1B and HNF4A in human pancreatic islet cell differentiation.
- (2023). Human induced pluripotent stem cells as a model for environmental impact on diabetes.
- (2022). Molecular mechanisms affecting islet like cell fate acquisition in differentiating iPSC derived β-like cells”.
- (2022). Mind your background!
- (2022). Know your background, know your data.
- (2022). Investigating the developmental role of HNF1A, HNF1B and HNF4A in human pancreatic islet cell differentiation.
- (2022). Investigating the developmental role of HNF1A in human pancreatic islet cell differentiation.
- (2022). Hnf1a is a key regulator of β-cell identity and function.
- (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.
More information in national current research information system (CRIStin)
2021-2024 Mapping predictive cancer signatures in vivo (funded by Norwegian Cancer Society, PI)
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, work package leader)
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