Investigating the molecular regulation of Pdx1 in the generation of new insulin-producing β-cells from stem/progenitor cells

PhD student: Theonie Demcollari
Supervisor at TUD: Nikolay Ninov
Supervisor at KCL: Rocio Sancho
Start date: 01.09.2017

Pdx1 is a major transcription factor required for the embryonic development and the adult neogenesis of beta cells. Pdx1 also plays a crucial role in adult beta cell function and has been linked to diabetes. Potent degradation pathways operate in order to regulate Pdx1 protein stability from embryogenesis until adulthood. Preliminary data from the Sancho lab demonstrate the strong regulation of proendocrine factors in progenitor cells, which makes the reprogramming process inefficient, resulting in dysfunctional beta cells. Understanding these regulatory mechanisms holds the key to explore new opportunities in regenerative medicine for diabetes. The main goal of this project is to delineate the molecular regulation of the proendocrine factor Pdx1 in stem cells, both adult and induced pluripotent. The project will provide insightful information on how to properly control Pdx1 levels, which will subsequently enable us to improve the efficiency of beta cell generation and achieve fully functional beta cells.

Publication:

Phenotypic plasticity in the pancreas: new triggers, new players. T.I. Demcollari, A.M. Cujba, R. Sancho. Curr Opin Cell Biol. 2017;49:38-46.