Stem cells and diabetes

Línea de investigación

Stem cells and diabetes.

Descripción

Pancreatic beta cells are the main source of the insulin hormone. These cells play a central role in the pathophysiology of diabetes, as reduced beta cell mass and/or function are associated with low insulin hormone levels, glucose intolerance, and diabetes. The objective of the group is to determine the genetic basis that determines beta cell mass and its proper function. On the one hand, we investigate genetic polymorphisms associated with the risk of diabetes, but we also study rare variants associated with monogenic diabetes. In both cases, we characterize the molecular mechanisms that explain the association between genetic variants and the disease. This is possible through the combined use of two cutting-edge techniques: 1) genetic editing using CRISPR/Cas9, which allows for studies of genetic loss of function as well as single nucleotide editing; and 2) differentiation of pluripotent stem cells, which allows us to ""simulate"" the development of the human pancreas in vitro and study the consequences of genetic perturbation at the level of pancreatic progenitors as well as differentiated beta cells.

The work plan will include the detailed study of a genetic variant associated with diabetes, which includes: 1) characterization of gene expression of interest in all stages of pancreatic development, 2) generation of haploinsufficient/knockout cell lines for the studied gene, 3) determining the effect of genetic variants at each stage of development, and if possible, 4) mechanistic studies focused on differential stages.

The ultimate goal of these studies is to generate knowledge about the genetic basis of beta cell dysfunction, which can allow for better stratification of patients with polygenic diabetes and evaluate new treatments for monogenic diabetes.

Contacto

Alberto Bartolomé Herranz.

Correo electrónico: abartolome@iib.uam.es.