CURRENT PROJECTS

 

Lineage decision between liver and pancreas

Our recent work has contributed to the understanding of early hepato-pancreatic development by defining transcriptional and signaling signatures underlining the lineage divergence of liver and pancreas (Rodriguez-Seguel et al. Genes Dev 2013; Kofent et al. Development 2016; Escot et al. Nat Comms 2018). We are now exploring cellular plasticity and population dynamics of hepato-pancreatic progenitors during lineage segregation using a combination of genetic lineage tracing, quantitative analysis, and mathematical modeling approaches.

 

Interplay between pancreatic epithelium and surrounding microenvironment(s)

During development pancreatic epithelial cells engage in concomitant morphogenetic and fate specification events that will give rise to the final organ architecture and functions. Cues from the surrounding microenvironment are known to influence the behavior of epithelial progenitors and orchestrate these concomitant events throughout pancreas development (Petzold et al. Development 2013; Cozzitorto, Spagnoli, Curr Top Dev Biol. 2019). Ongoing work in the lab. focuses on the composition of the pancreatic microenvironment and the interplay between components of the surrounding microenvironment and the epithelium.

 

Lineage Reprogramming to generate pancreatic beta-cells

Learning how to reprogram cell identity not only holds tremendous potential for regenerative medicine, but also represents an excellent platform for elucidating developmental biology. In my lab, we have defined a novel strategy for reprogramming mouse liver cells into pancreas progenitors based on one developmental regulator of this fate decision (Heinrich et al Nat Cell Biol. 2015; Cerda-Esteban et al. Nat Comms. 2017). This represents a powerful platform for investigating mechanistic aspects of cellular identity and plasticity and provides a starting point for production of human pancreatic beta-cells for therapeutic use in patients.

 

iPSC modelling of human pancreatic development

Maintenance of cellular identity is required to continuously support adult organ function and prevent diseases. We study molecular defects in human β-cell development and dysfunction and how β-cell de-differentiation might result into disease (Gong et al 2013; Simaite et al. Diabetes 2015; Kofent et al. Semin Cell Dev Biol. 2016).