Cell & Regenerative Biology Department
Epigenetics, somatic cell reprogramming, cell fate change
2118, 1120 Vivarium-Wid-Mir
309 N Orchard St
Madison, WI 53715
Transcriptional Mechanisms; Developmental Biology & Regenerative Medicine
It is known that the chromatin structure of pluripotent cells differs from that of differentiated cells. I am particularly interested in how the reprogramming factors induce this chromatin change and whether they occur in a hierarchical manner globally and at specific loci. I have employed proteomic techniques to determine global changes in histone posttranslational modifications that occur in somatic, partially reprogrammed ( pre-iPS) and iPS cells. We are employing genomic techniques to locate where these modifications are enriched in the genome, and also test the functional consequence of perturbing the levels of these histone modifications by assessing their effect on somatic cell reprogramming efficiency, which is known to be poor. We have also combined a chromatin modifioer and a signaling inhibitor to convert pre-iPSCs to iPSCs at very high efficiency- and by using next gen sequencing methods, derived a regulatory network for the gain of pluripotency. We are in the process of testing the function of key nodes in the network with loss and gain of function assays. Ultimately these studies will lead to an understanding of how cell fate is maintained.