The overall aim of the research in Integrative Physiology is to discover and validate targets important in metabolic disease, for example glucose homeostasis and Type 2 diabetes mellitus.
Research group leader
Excecutive Assistant, Research group leader
Deputy Research group leader
Integrative Physiology, Karolinska Institutet
Biomedicum, C4, Solnavägen 9, 171 77 Stockholm
Our central hypothesis is that alterations in insulin signal transduction to glucose transport contribute to the profound impairment in whole body glucose homeostasis and Type 2 diabetes pathogenesis and that identification of the defects can lead to the development of new therapeutic strategies to prevent and cure this disease. Research activities are divided into two main objectives:
1) Development of target identification platforms using microarray, proteomics and bioinformatics to identify dysregulated genes in healthy and diabetic patients or genetically modified model systems.
a) Gene expression profiling is performed in healthy and Type 2 diabetic subjects and defined genetic models to create a fingerprint of dysregulated genes associated.
b) Bioinformatics and predictive pathway analysis is performed to identify mechanism for insulin action and resistance.
c) Proteomics is being developed to validate the target genes identified in the gene expression profile.
2) Functional genomics is used to assign a physiological role to the identified targets using cellular (in vivo siRNA) and whole-body (genetically modified mice) models. We are developing:
a) high-through-puts screen in human skeletal muscle cells to silence or overexpress candidate genes to establish the functional impact on metabolism.
b) medium-through-put screens (electroporation) to determine the consequence of gene silencing or overexpression on the whole-body metabolic phenotype at tissue (organ) level.
c) tissue-specific gene knockout or transgenic models to provide proof-of concept that the identified gene(s) and the pathway(s) they regulate play a causative or preventive role in the development of type 2 diabetes.
More information about the ongoing research at Integrative Physiology, FYFA