Dawn Carone will be arriving in Fall 2014. Dawn’s lab studies human nuclear structure and the elements that contribute to maintaining nuclear integrity. She uses a targeted combination of approaches including state of the art molecular cytology with quantitative microscopy, molecular biology and genomics in her investigations.
Uncovering functions for the junk of the human genome: Over ten years ago, the human genome was sequenced, however there is still much of the genome sequence that is a mystery. High-copy repetitive elements comprise roughly half of our genome, and the bulk of these are unexplored and understudied. The goal of Dawn’s research is to uncover the many potentially important functions for the repetitive half of the genome as it relates to nuclear structure and gene regulation. As cutting-edge genomics studies are increasingly generating large amounts of data on the interactions between DNA, RNA and protein, it is becoming increasingly apparent that there is widespread transcription of repetitive sequences and these have critical gene and nuclear regulatory functions. As these functions are uncovered, it is becoming clear that misregulation of repeat-derived transcripts has wide-ranging implications for cancer, and many other diseases. Dawn’s lab is developing new techniques to release this nuclear-bound repeat RNA in order to sequence, study, and, ultimately, manipulate it. In order to do this, she has developed quantitative methods to compare in situ nuclear RNA signals to extracted RNA.
Misregulation of satellite DNA in cancer and heterochromatin instability: Another project in the lab is focused on a subset of repetitive elements, satellite DNA, which are tandemly repeated near the centromeres of all human chromosomes. We have identified a specific satellite sequence that is aberrantly expressed in a wide range of human cancer cell lines and tissues, and may be a potential biomarker of cancer. This satellite is not only aberrantly expressed, but accumulates within nuclei of cancer cells and binds regulatory proteins, which is linked to genome methylation status. We are currently trying to understand the mechanisms underlying the satellite misregulation and the impact this has on regulation of the cancer genome more broadly. Satellite misregulation is a potential read-out for global misregulation of highly-packaged and normally compartmentalized heterochromatin.