Research Group KALKHOVEN

Faculty of Medicine, University Medical Centre Utrecht, Dept. of Metabolic & Endocrine Diseases
Contact: Dr. Eric Kalkhoven
E-mail: e.kalkhoven@umcutrecht.nl
Website: http://www.metabole-ziekten.nl/

General research focus: Transcription regulation in adipogenesis

We focus on the regulation of gene expression during adipogenesis (fat cell differentiation):
We aim to understand the role of acetyltransferases in adipogenesis. Acetyltransferases, like the coactivators CBP and p300, can regulate gene expression by acetylating histone proteins in the promoter region of a target gene. The importance of this process in development and homestasis is exemplified by the fact that heterozygous mutations in the CBP gene cause Rubinstein-Taybi syndrome, a congential developmental disorder. Recently, we have found that the acetyltransferase TIP60 functions as a transcriptional coactivator for the PPARγ protein, one of the key transcription factors in adipogenesis. We are currently elucidating the molecular mechanism behind this effect. In the near future we also wish to examine the role of other acetyltransferases in PPARγ signaling and adipogenesis.
A second line of research concerns investigations into the structure and function of the nuclear hormone receptors PPARγ and δ in adipogenesis. We have recently characterized a mutated form of PPARγ, as found in a patient with familial partial lipodustrophy (FPL), and found that this mutation (R425C) impairs the activity of PPARγ at multiple levels. Future work is aimed at elucidating structure-function relationships in PPARγ, as well as the related protein PPARδ.

Techniques: general molecular biology, protein biochemistry, DNA-protein and protein-protein interaction assays, luciferase reporter assays, cellular differentiation assays, retroviral transduction, RNAi.

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