B.S. 1998, University of Lethbridge; Ph.D. 2006, University of Calgary; Post-Doctoral Fellow 2006-2011, Harvard University, Dept. of Molecular and Cellular Biology
Uncovering new genetic and epigenetic mechanisms shaping brain function, behavioral development and mental illness.
In part, adult health and behavior is a reflection of developmental processes and early life experiences. Uncovering early life processes that influence adult behavior and health may fundamentally impact our understanding of obesity, neurological and psychiatric diseases, as well as of broader societal issues related to diet, parenting, education, and socioeconomic policies.
My laboratory is focused on understanding epigenetic and genetic pathways that influence feeding circuits and foraging behavior (eg. assessing risk versus reward). In particular, we are working to uncover epigenetic regulatory pathways that program gene expression in the brain during early life to influence adult brain function, behavior and disease susceptibility.
The lab has a major interest in imprinting. Maternally and paternally inherited chromosomes are not functionally equivalent due to a heritable epigenetic mode of gene regulation, called genomic imprinting. Imprinted genes are unique, because they preferentially express either the maternally or the paternally inherited gene copy (allele), instead of expressing both parental alleles equally. We have developed a genome-wide approach to study imprinting using next generation sequencing. To date, our analyses have uncovered a vast array of complex parental effects and indicate the existence of distinct maternal and paternal gene expression programs in the brain (Gregg et al. Science 2010a, Gregg et al. Science 2010b). We discovered that 60% of imprinted genes express in the developing brain preferentially express the maternally inherited allele. However, in the adult brain, 70% of imprinted genes preferentially express the paternal allele.
Currently, we are working to further understand the nature and functions of maternal and paternal gene expression programs in feeding circuits of the brain. We utilize next generation sequencing technologies (transcriptomics and epigenomics), bioinformatics, mouse genetics, molecular biology, histology and imaging technologies, as well as behavior assays to address a variety of questions:
1. What is the nature and function of maternal and paternal gene expression programs in the brain? How do they influence feeding and foraging behaviors?
2. What are the regulatory mechanisms that govern maternal and paternal gene expression programs?
3. Do environmental factors (eg. diet) influence maternal and/or paternal gene expression programs in the brain?
4. How has imprinting evolved to regulate brain function and behavior in other species? What is the nature of the human brain imprintome? What is the relevance of imprinting to human diseases and disorders?