Medical epigenetics

TOMAS EKSTRÖM TEAM

 

About

The genetic material, or genome, which is identical in all cells of an individual, is composed of DNA and associated proteins, which together make up the chromatin. Chromatin is nessecary for the packaging of the genetic material in every cell nucleus of the organism, as well as for the regulation of gene programs, which are different in all cell types and which can be altered in disease. This is done partly by employing epigenetic mechanisms.

We are studying the integration between these mechanisms, the genome and environmental exposures in order to understand risks of autoimmune inflammatory chronic diseases that affect 1/3 of the Swedish population, a great burdon on individuals and society. The coordination of the genome with the epigenetic make-up is likely of great importance.

Rheumatoid arthritis (RA), a systemic inflammatory disease primarily affecting the flexible joints, and multiple sclerosis (MS), a neurological disease affecting the function of nerves in the central nervous system, are both chronic autoimmune diseases associated with inflammation.

Our research is connecting individual epigenetic profiles with genetic background, lifestyle and disease risks. We try to find epigenetic molecular causes to why individuals with certain genetic make-up combined with certain environmental exposures are affected by RA or MS, and why therapy responses are different among affected individuals. To achieve this, we use advanced technology and bioinformatics with clinical patient material.

Selected publications

Almgren M, Schlinzig T, Gomez-Cabrero D, Gunnar A, Sundin M, Johansson S, et al. Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health? Am. J. Obstet. Gynecol. 2014 Nov;211(5):502.e1-8.

Liu Y, Aryee M, Padyukov L, Fallin M, Hesselberg E, Runarsson A, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat. Biotechnol. 2013 Feb;31(2):142-7.

Esteki-Zadeh A, Karimi M, Strååt K, Ammerpohl O, Zeitelhofer M, Jagodic M, et al. Human cytomegalovirus infection is sensitive to the host cell DNA methylation state and alters global DNA methylation capacity. Epigenetics 2012 Jun;7(6):585-93.

Melas P, Rogdaki M, Ösby U, Schalling M, Lavebratt C, Ekström T. Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset. FASEB J. 2012 Jun;26(6):2712-8.

Arzenani M, Zade A, Ming Y, Vijverberg S, Zhang Z, Khan Z, et al. Genomic DNA hypomethylation by histone deacetylase inhibition implicates DNMT1 nuclear dynamics. Mol. Cell. Biol. 2011 Oct;31(19):4119-28.