Research Overview

Epigenetic inheritance is defined as the transmission of traits independent of DNA sequence. Three well-studied examples of epigenetic inheritance are paramutation in maize, transvection in Drosophila and genomic imprinting in mammals and seed-bearing plants. Genomic mprinting can be broadly defined as the unequal representation or function of genes or chromosomes based on parental origin. It takes many forms and is widely seen in both plants and animals. The epigenetic marks, or imprints, on DNA may take the form of specific patterns of cytosine methylation or of specified chromatin domains. These marks are then interpreted during embryonic development and evinced as differential transcriptional states of marked genes.

The primary focus of research in my lab is genomic imprinting that is manifest as the transcriptional silencing of genes based on parental origin. Some imprinted genes are transcriptionally silent when inherited from the father; others are transcriptionally silent when inherited from the mother. Our primary model organisms are mammals, but we include a broad range of vertebrate animals in our studies. A recent census of imprinted genes in mammals identified slightly more than 80 imprinted loci, but there are likely hundreds more yet to be identified. Genetic and epigenetic mutations resulting in disruption of normal imprinted silencing of genes underlies many human diseases and cancers.To advance our understanding of genomic imprinting, my laboratory addresses three fundamental questions: 1) How and why did genomic imprinting evolve? 2) What are the consequences of genomic imprinting for embryonic development, specifically neurological development? 3) What are the molecular mechanisms that render a gene transcriptionally silent in a parent specific manner?