SciLifeLab The Svedberg seminar series 2014-02-24
Nencki Institute of Experimental Biology, Laboratory of Molecular Neurobiology, Neurobiology Center, Warsaw, Poland
Bozena Kaminska is head of the Laboratory of Molecular Neurobiology at the Nencki Institute with interests in transcriptional and epigenetic mechanisms underlying brain tumor pathogenesis and neuroinflammation. Her work merges molecular and cell biology, animal models and computational analyses to study gene regulatory networks, chromatin structure and signaling pathways in brain injury and tumor-related inflammation.
“Epigenetic memory of polarized microglia in brain pathologies”
Microglia are innate immune cells residing in the central nervous system and their activation is observed in virtually all neurological diseases. These cells accumulate at the sites of brain infection or injury and initiate inflammation that can turn pathological when is chronic or uncontrolled. On the other, microglia infiltrate malignant gliomas where they switch to a pro-invasive phenotype and support tumor progression. Our studies on microglia exposed to immunomodulator or glioma demonstrate activation of distinct signaling, transcriptional and metabolic pathways. As global changes associated with establishment of different phenotypes may involve epigenetic mechanisms, we studied DNA methylation and histone modifications. Tested genes were not methylated and changes in histone modifications were associated with gene repression that suggests their role consolidation of the polarized phenotype. Inhibitors of epigenetic enzymes modulated establishment of activated phenotype and gene expression profiles. Inflammatory activation seems to be a “default response” of microglia, actively suppressed and misused by a tumor for its benefit.
Host: Jan Komorowski