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.  

ELMED303 Future medicine

LAS302 Mammal Science Course

Academic article

• Kenichiro Furuyama; Simona Chera; Leon van Gurp et al. (2019). Diabetes relief in mice by glucose-sensing insulin-secreting human α-cells. (external link)
• Magnus Berle; Luiza Ghila; Heidrun Vethe et al. (2018). Novel protein signatures suggest progression to muscular invasiveness in bladder cancer. (external link)
• Chencheng Wang; Shadab Abadpour; Petter Angell Olsen et al. (2024). Glucose Concentration in Regulating Induced Pluripotent Stem Cells Differentiation Toward Insulin-Producing Cells. (external link)
• Luiza Ghila; Yngvild Bjørlykke; Thomas Aga Legøy et al. (2020). Bioinformatic analyses of miRNA-mRNA signature during hiPSC differentiation towards insulin-producing cells upon HNF4α mutation. (external link)
• Preksha Bhagchandani; Charles A. Chang; Weichen Zhao et al. (2022). Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes. (external link)
• Shayla Sharmine; Thomas Aga Legøy; Lucas Unger et al. (2025). Caloric Restriction Substantially Improves Glucose Regulation in Mice With Hnf1a‐Deficient Beta‐Cells. (external link)
• Lucas Unger; Ulrik Larsen; Shayla Sharmine et al. (2025). Efficient cytoplasmic cell quantification using a semi-automated FIJI-based tool. (external link)
• Thomas Aga Legøy; Andreas Frøslev Mathisen; Zaidon Salim et al. (2020). In vivo environment swiftly restricts human pancreatic progenitors toward mono-hormonal identity via a HNF1A/HNF4A mechanism. (external link)
• Thomas Aga Legøy; Luiza Ghila; Heidrun Vethe et al. (2019). In vivo hyperglycemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress. (external link)
• Lucas Unger; Andreas Frøslev Mathisen; Simona Chera et al. (2024). The GLI code controls HNF1A levels during foregut differentiation. (external link)
• Thomas Aga Legøy; Heidrun Vethe; Shadab Abadpour et al. (2020). Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling. (external link)
• June Helen Gudmestad; Lucas Unger; Joao A Paulo et al. (2025). Endocrine-disrupting chemical exposure during differentiation alters the proliferation–maturation balance in stem-cell islets. (external link)
• Andreas Frøslev Mathisen; Shadab Abadpour; Thomas Aga Legøy et al. (2023). Global proteomics reveals insulin abundance as a marker of human islet homeostasis alterations. (external link)
• Laura Maria Daian; Gabriela Tanko; Andrei Mircea Vacaru et al. (2023). Modulation of Unfolded Protein Response Restores Survival and Function of β-Cells Exposed to the Endocrine Disruptor Bisphenol A. (external link)
• Andreas Frøslev Mathisen; Ulrik Larsen; Natalie Aasen Kavli et al. (2024). Moderate beta-cell ablation triggers synergic compensatory mechanisms even in the absence of overt metabolic disruption. (external link)
• Yngvild Bjørlykke; Anne Mette Søviknes; Laurence Hoareau et al. (2019). Reprogrammed cells display distinct proteomic signaturesAssociated with colony morphology variability. (external link)
• Andreas Frøslev Mathisen; Thomas Aga Legøy; Ulrik Larsen et al. (2024). The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop. (external link)
• Manuel Carrasco Fernandez; Chencheng Wang; Anne Mette Søviknes et al. (2022). Spatial Environment Affects HNF4A Mutation-Specific Proteome Signatures and Cellular Morphology in hiPSC-Derived β-Like Cells. (external link)
• Heidrun Vethe; Luiza Ghila; Magnus Berle et al. (2019). The effect of WnT pathway modulators on human iPSC-derived pancreatic beta cell maturation. (external link)
• Heidrun Vethe; Thomas Aga Legøy; Shadab Abadpour et al. (2019). Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling. (external link)
• Valentina Cigliola; Luiza Ghila; Fabrizio Thorel et al. (2018). Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon+ α-cells. (external link)
• Heidrun Vethe; Yngvild Bjørlykke; Luiza Ghila et al. (2017). Probing the missing mature β-cell proteomic landscape in differentiating patient iPSC-derived cells. (external link)
• Andreas Frøslev Mathisen; Andrei Mircea Vacaru; Lucas Unger et al. (2024). Molecular profiling of NOD mouse islets reveals a novel regulator of insulitis onset. (external link)
• Chencheng Wang; Shadab Abadpour; Aleksandra Aizenshtadt et al. (2024). Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling. (external link)
• Lucas Unger; Luiza Mihaela Ghila; Simona Chera (2024). Targeted Gene Silencing by Using GapmeRs in Differentiating Human-Induced Pluripotent Stem Cells (hiPSC) Toward Pancreatic Progenitors. (external link)
• Luiza Ghila; Thomas Aga Legøy; Andreas Frøslev Mathisen et al. (2021). Chronically elevated exogenous glucose elicits antipodal effects on the proteome signature of differentiating human ipsc-derived pancreatic progenitors. (external link)
• Jakub Vasicek; Ksenia Kuznetsova; Dafni Skiadopoulou et al. (2024). ProHap enables human proteomic database generation accounting for population diversity. (external link)
• Luiza Ghila; Thomas Aga Legøy; Simona Chera (2021). A Method for Encapsulation and Transplantation into Diabetic Mice of Human Induced Pluripotent Stem Cells (hiPSC)-Derived Pancreatic Progenitors. (external link)

Lecture

• Thomas Aga Legøy; Andreas Frøslev Mathisen; Joao Paulo et al. (2024). Impact of diabetogenic signals from endocrine disrupting chemicals on a HNF1A cell model. (external link)
• Luiza Mihaela Ghila (2022). Mapping tumour heterogeneity and predictive cancer signatures in vivo. (external link)
• Lucas Unger; Thomas Aga Legøy; Luiza Mihaela Ghila et al. (2023). Exploring the role of transcription factors HNF1A, HNF1B, and HNF4A in human induced pluripotent stem cell-derived pancreatic islet cell differentiation. (external link)
• Andreas Frøslev Mathisen; Thomas Aga Legøy; Ulrik Larsen et al. (2023). Hnf1a Is An Important Regulator in Ageing And Maturation Of Pancreatic Islets. (external link)
• Thomas Aga Legøy; Andreas Frøslev Mathisen; Joao Paulo et al. (2024). Impact of endocrine disruptors on MODY3 iPSCs differentiation toward SC-islets – potential diabetogens. (external link)
• Luiza Mihaela Ghila (2022). Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors. (external link)
• Lucas Unger; Thomas Aga Legøy; Simona Chera et al. (2023). Exploring the role of transcription factors HNF1A, HNF1B, and HNF4A in human pancreatic islet cell differentiation. (external link)

Conference poster

• Md Kaykobad Hossain; Altanchimeg Altankhuyag; Joao Paulo et al. (2024). Investigating the tissue injury sensing and regenerative response in bladder urothelium. (external link)
• Md Kaykobad Hossain; Altanchimeg Altankhuyag; Thomas Aga Legøy et al. (2024). Short-term BBN treatment alters the proteomic profile of mouse bladder. (external link)
• Andreas Frøslev Mathisen; Thomas Aga Legøy; Luiza Mihaela Ghila et al. (2022). Know your background, know your data. (external link)
• Lucas Unger; Thomas Aga Legøy; Luiza Mihaela Ghila et al. (2022). Investigating the developmental role of HNF1A in human pancreatic islet cell differentiation. (external link)
• Chencheng Wang; Shadab Abadpour; Alexandra Aizenshtadt et al. (2021). Glucose during in vitro pancreatic beta cells regeneration: friends or for?. (external link)
• Thomas Aga Legøy; Andreas Frøslev Mathisen; Joao Paulo et al. (2023). Human induced pluripotent stem cells as a model for environmental impact on diabetes. (external link)
• Shayla Sharmine; Thomas Aga Legøy; Andreas Frøslev Mathisen et al. (2023). Mapping islet architecture changes upon high fat diet challenge in a HNF1A-MODY mouse model. (external link)
• Lucas Unger; Luiza Mihaela Ghila; Simona Chera (2022). Investigating the developmental role of HNF1A, HNF1B and HNF4A in human pancreatic islet cell differentiation. (external link)
• Lucas Unger; Thomas Aga Legøy; Luiza Mihaela Ghila et al. (2024). Exploring hedgehog signaling and HNF1A Crosstalk in HNF1A-MODY stem cell islets. (external link)
• Shayla Sharmine; Luiza Mihaela Ghila; Simona Chera (2024). Short-term effect of Somatostatin Modulators on Glycemic Control in MODY mice. (external link)
• Md Kaykobad Hossain; Altanchimeg Altankhuyag; Thomas Aga Legøy et al. (2024). Dynamic proteome profiling detects progressive alterations induced by BBN in the mouse bladder. (external link)
• Lucas Unger; Thomas Aga Legøy; Andreas Frøslev Mathisen et al. (2023). Investigating the developmental role of HNF1A, HNF1B and HNF4A in human pancreatic islet cell differentiation. (external link)
• Ulrik Larsen; Andreas Frøslev Mathisen; Natalie Aasen Kavli et al. (2024). Investigating stress-induced islet cell proliferation following partial insulin-secreting β-cell ablation in mice. (external link)
• Andreas Frøslev Mathisen; Thomas Aga Legøy; Luiza Mihaela Ghila et al. (2022). Hnf1a is a key regulator of β-cell identity and function. (external link)
• Andreas Frøslev Mathisen; Thomas Aga Legøy; Luiza Mihaela Ghila et al. (2022). Mind your background!. (external link)
• Lucas Unger; Andreas Frøslev Mathisen; Thomas Aga Legøy et al. (2024). Deciphering the HNF1A and Hedgehog Signaling Crosstalk during Stem Cell Islet differentiation. (external link)
• Md Kaykobad Hossain; Altanchimeg Altankhuyag; Thomas Aga Legøy et al. (2023). Mapping predictive bladder cancer signatures in a mouse model. (external link)
• Thomas Aga Legøy; Lucas Unger; Joao A. Paulo et al. (2024). Exposure to Endocrine Disrupting Chemicals During Differentiation of HNF1A-MODY SC-islets has an Adverse Effect on Cell Fitness. (external link)
• Thomas Aga Legøy; Andreas Frøslev Mathisen; Hanne Scholz et al. (2022). Molecular mechanisms affecting islet like cell fate acquisition in differentiating iPSC derived β-like cells”. (external link)

Conference lecture

• Andreas Frøslev Mathisen; Thomas Aga Legøy; Ulrik Larsen et al. (2023). Islet maturation and ageing is governed by the Hnf1a transcription factor. (external link)
• Ulrik Larsen; Andreas Frøslev Mathisen; Natalie Aasen Kavli et al. (2024). Partial insulin-producing β-cell ablation induces compensatory proliferation in mouse pancreatic islets. (external link)
• Thomas Aga Legøy; Lucas Unger; Joao A. Paulo et al. (2024). Environmental neglect: endocrine disruptors as underappreciated but important diabetogens in HNF1A-MODY cell model. (external link)

Editorial/Leader article

• Shayla Sharmine; Luiza Mihaela Ghila (2025). Targeting Inflammation in Type 2 Diabetes: The Emerging Role of Decorin. (external link)
• Luiza Mihaela Ghila; Kenichiro Furuyama; Shane T. Grey et al. (2022). Editorial: Beta-Cell Fate: From Gene Circuits to Disease Mechanisms. (external link)

Professional article

• Md Kaykobad Hossain; Lucas Unger; Ulrik Larsen et al. (2025). Mapping the initial effects of carcinogen-induced oncogenic transformation in the mouse bladder. (external link)

Conference abstract

• Chencheng Wang; Shadab Abadpour; Alexandra Aizenshtadt et al. (2021). 402.2: High Glucose Concentration Increases KATP Channel Activity but Suppresses Mitochondrial Respiration Ability in Insulin-producing Cells Regenerated From Stem Cells. (external link)

Popular science article

• Preksha Bhagchandani; Charles Chang; Weichen Zhao et al. (2021). Islet transplantation tolerance in animals with defined histocompatibility and diabetes. (external link)

Academic literature review

• Valentina Cigliola; Luiza Ghila; Simona Chera et al. (2019). Tissue repair brakes: A common paradigm in the biology of regeneration: Concise review. (external link)

See a complete overview of publications in 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