Assistant Professor of Internal Medicine
PhD, University of Alabama, Birmingham
Post Doctoral, Harvard Medical School and Howard Hughes Medical Institute
Education/Training Program Affiliations
Biosciences Graduate Program
Interdisciplinary Graduate Program in Genetics
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Neuroscience
Embryonic stem (ES) cells are endowed with two distinguishing properties, they can regenerate themselves indefinitely (self-renewal) and simultaneously give rise to all tissues in the body (pluripotency). Broadly, the long-term objective of my laboratory is to identify and characterize transcription factors and nuclear proteins that regulate self-renewal and pluripotency. In one project, we are investigating the transcriptional and epigenetic regulation of the nuclear factors GDF3, Dppa3 and the transcription factor Nanog. This cluster of genes lie in the same genomic region, or locus, and this Nanog locus appears to constitute a functional module that is important for pluripotency. Nanog locus gene expression and chromatin structure are both highly dependent on the expression of another pluripotency transcription factor, Oct4. Both Nanog and Oct4 are essential for reprogramming adult cells to a pluripotent state. Additionally, the short arm of human chromosome 12 that houses the Nanog locus is the most frequently amplified region in human germ cell tumors, and appears to be an essential determinant of uncontrolled cell growth in these and several other types of cancer. Study of Nanog, Oct4 and other reprogramming factors will be important to help us understand how the property of pluripotency can be reliably and safely conferred upon non-pluripotent cell types. To achieve our goals, we are employing the tools of molecular biology, biochemistry and proteomics. Additionally, we are using conditional gene targeting approaches and RNA interference (RNAi) to engineer new ES cell lines and mouse models.
With less than 5 percent of the mammalian genome responsible for expressing genes, many of the factors vital for pluripotency bind DNA at regulatory elements, known as enhancers, which are far away from gene promoter regions. Another topic of study in the laboratory is determining how pluripotency factor bound enhancers bridge long distance interactions within the Nanog locus, and how this regulates gene expression.
Date Last Modified: 06/07/2014 -