Tony (Anton) Krumm, PhD
The differentiation of stem cells into specialized cell types is controlled by genetic and epigenetic mechanisms. There is compelling evidence that epigenetic alterations play a critical role in the pathogenesis of cancer, diabetes, and heart disease. This lab is studying chromatin structure and genome-wide distribution of factors required for epigenetic control of gene expression and genomic imprinting. Our studies include research on chromosomal elements that shield transcription domains from the advance of silencing heterochromatic structures into the gene domain. This barrier function is often accompanied by an insulator activity that prevents inappropriate gene activation through adjacent enhancer elements. Together, these elements function as gatekeepers that either permit or prevent access of regulatory signals to transcription domains. The focus of this lab is to reveal the molecular mechanisms by which these elements contribute to the dynamic changes of gene expression during normal and pathological cell differentiation.
Normal development and differentiation of stem cells requires maintenance of allele-specific gene expression at imprinted gene loci. Monoallelic expression (maternal or paternal) at a subset of genetic loci also involves gatekeepers that inhibit the interaction of transcriptional enhancers with gene promoters. By mapping specific epigenetic signatures across the genome, we identify genes transcribed on either the maternal or paternal allele across the human genome. Generating a catalogue of epigenetic alterations will provide molecular signatures that are essential to the development of novel tools in the diagnosis and therapy of human disease.