I am interested in the mechanisms of abnormal gene inactivation and the relevance of these events to cancer. Abnormal gene inactivation results from two distinct types of events. The first is DNA mutation, which represents a change in the structure of DNA that alters expression of a given gene. The second type of event is epigenetic silencing, which involves loss of gene expression without alteration of the gene sequence. With regards to mutational events, we are interested in both endogenous and exogenous genotoxins that can affect the frequency and types of mutations that occur within the animal. A current focus is on how accelerated particles in space cause large-scale genomic damage that could affect astronauts during prolonged space travel. Our work with epigenetic silencing focuses on how silencing is initiated and determining the pathways that cause active genes to become aberrantly turned off.
Expresses tTA transactivator protein that activates pTRE promoter and than bind doxycycline. When combined with pTRE-HPRT, it expresses human HPRT cDNA that can be repressed by addition of doxycycline to the drinking water.
Mouse model is used to induce epigenetic gene silencing at target locus.