At the Sancho Lab, we are excited to uncover how the pancreas works and use this knowledge to develop new and better treatments for diabetes. When insulin producing cells are lost or stop working, the body can no longer control blood sugar properly. We explore whether other cells in the pancreas can be encouraged to take on this role and restore function. By growing new insulin producing cells in the laboratory, we aim to create powerful new therapeutic options. Using stem cells derived from patients, we recreate aspects of pancreatic disease to better understand its causes and move towards more personalised treatments. We also work to make these lab grown cells stronger, so they can survive and function after transplantation. Together, our research is opening new possibilities to repair the pancreas and transform the lives of people living with diabetes.
The research in the Sancho Lab is funded by:
Our Research
Searching for a place to do your PhD or PostDoc?
In the Sancho Lab we always welcome highly motivated PhD students and Postdocs with great ideas to join the team! If you share our research interests and would like to join the Sancho Lab please send your informal enquiry to rocio.sancho@kcl.ac.uk.
Our Projects
Rewiring pancreatic cell fate to enable regeneration in diabetes
Image: Protein expression of HNF1 (Green), CK19 (Red), DAPI (Blue). Credit: Christopher Lambert, PhD Student
Diabetes arises from the loss or dysfunction of insulin producing beta cells, yet the pancreas has a strikingly limited capacity to regenerate. Our research addresses a central question in regenerative biology, can pancreatic cell identity be reprogrammed to restore function? We investigate how cell fate decisions are controlled in both human iPSC derived and adult pancreatic progenitors, integrating advanced 3D culture systems, single cell transcriptomics, and computational modelling. This approach enables us to define the molecular logic governing cellular plasticity and to identify strategies to unlock regenerative potential. By bridging discovery science with translational ambition, this work aims to inform next generation regenerative therapies for diabetes and related pancreatic disorders.
Fine tuning endocrine commitment through post translational control
Image: Insulin (Green); Somatostatin (Red) and DAPI (blue) in iPSCs differentiated to β cells without (left) or with (right) inhibition of NGN3-stabilising deubiquitinase USP7. Credit: Teodora Manea, PhD student
The transition from pancreatic progenitor to endocrine cell is orchestrated by key transcription factors, including NGN3 and PDX1. While their transcriptional roles are well established, the dynamic control of their activity at the protein level remains poorly understood. Our work focuses on uncovering novel post translational mechanisms that regulate the stability and function of these proendocrine factors. We are identifying pathways that modulate NGN3 and PDX1 degradation and activity, thereby shaping endocrine lineage commitment. This layer of regulation offers new opportunities to enhance the efficiency and fidelity of beta cell generation in vitro, with direct relevance for cell based therapies.
Patient specific stem cell models to decode diabetes and pancreatic disease
To uncover the molecular basis of human pancreatic disorders, we use patient derived induced pluripotent stem cells as a platform for disease modelling. While a major focus is on monogenic diabetes such as MODY3, this framework extends to a wider range of pancreatic diseases. By combining CRISPR based genome engineering with directed differentiation towards pancreatic lineages, we investigate how defined genetic alterations influence cell identity, function, and disease phenotypes. We have established expandable 3D pancreatic progenitor organoid systems that enable robust and physiologically relevant modelling. Through integrated transcriptomic and genomic analyses, we have identified previously unrecognised roles of key regulatory genes such as HNF1A. These approaches provide insight into shared and disease specific mechanisms, supporting the development of targeted and precision therapies.
Image: Pdx1 (Red); CK19 (Green); DAPI (Blue) in iPSC-derived pancreas progenitors organoids. Credit: Ana Maria Cujba, PhD student
Enhancing the resilience of stem cell derived beta cells for transplantation
A major challenge for cell replacement therapies is the long term survival and function of transplanted beta cells within a hostile environment shaped by immune attack and cellular stress. We develop strategies to enhance the resilience of iPSC derived beta cells by targeting both immune recognition and intrinsic survival pathways. This includes modulating antigen presentation and immune signalling to reduce vulnerability to immune mediated damage, alongside strengthening cellular stress responses, metabolic fitness, and resistance to apoptosis. By integrating stem cell biology with immunology and cell survival mechanisms, this work aims to generate durable, functional beta cells capable of sustained performance after transplantation, advancing the clinical potential of regenerative therapies for diabetes.