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Bradley R. Cairns

Distinguished Professor of Oncological Sciences

B.S. Lewis and Clark College

Ph.D. Stanford University

Research

References

brad.cairns@hci.utah.edu

Brad Cairns' Lab Page

Brad Cairns' PubMed Literature Search

Research

We are interested in epigenetics and chromosome dynamics; how chromatin regulates transcription to influence processes like cell growth, development, and cancer. Questions addressed in our lab include: What is the state of the genome and chromosomes at the'start'of development - how is the genome packaged and poised in germ cells (sperm and egg) to prepare for embryo development - how do chromatin changes guide gene expression and embryo development - and how is chromatin misregulated in cancer? We approach these and other biological problems with a variety of techniques including biochemistry, genetics, and genomics (microarray and ChIP sequencing). We address these biological problems in yeast, zebrafish, and human cells.

Chromatin is a remarkably dynamic material; chromosomal structures formed to silence transcription are remodeled and modified to enable transcription in response to cell signals. The primary unit of chromatin structure is the nucleosome. Chromatin transitions are mediated by protein complexes that either reposition nucleosomes, covalently modify nucleosomes, or methylate the DNA – and there is coordination among them. For example, Remodeler complexes recognize particular covalent modifications on nucleosomes, and then use ATP hydrolysis to reposition nucleosomes on the DNA, thereby revealing the underlying sequence to transcriptional regulators. Also, DNA methylation leads to a heritable form of gene silencing, but is regulated by histone modification patterns. We aim to understand these relationships.

Remodeler mechanism and regulation. We have established that Remodelers pump DNA around nucleosomes to expose DNA to transcription factors using ATP-dependent DNA translocation, and Cedric Clapier is testing how DNA'waves' this process is regulated using biochemical and single-molecule approaches. Remodelers also bear proteins related to actin, and we are now revealing their role in regulating the DNA pumping 'engine'. Tim Parnell is working on how Remodelers eject nucleosomes from gene promoters to help promote transcription. Alisha Schichter and Maggie Kasten are investigating how Remodelers recognize particular histone modifications to move the right nucleosome. Andrew Oler and Ravi Alla are focusing on how chromatin regulates Pol III genes, which make many important noncoding RNAs.

Epigenetics; the regulation of DNA and RNA methylation/demethylation. Itrat Jafri, Graham Hickey and Christian Pflueger are investigating how DNA methylation dynamics help regulate development in zebrafish, and how misregulation impacts cancer. We are also establishing a Center for Zebrafish Epigenetics and Chromatin (CZECH)(with David Jones' lab); which will serve as a resource for genomics and epigenetic work on the zebrafish for the entire community. Magdalena Potok is examining dynamic DNA methylome of early zebrafish embryos, while Mengyao Tan explores the transcription factors that set up the transcriptome of early embryos – both through sophisticated genomics approaches. Vahid Khodammi is exploring how RNA methylation is utilized in gene regulation and epigenetics, and Archana Yerra on the roles of noncoding RNAs.

Germ Cell Chromatin. Sue Hammoud, Chongil Yi, Jahnvi Purwar, Shan-Fu Wu, and Magdalena Potok are working on germline chromatin and the mechanisms of poising genes in sperm and eggs for activation or repression in embryos.

References