Speaker: Alika Maunakea, Ph.D.
Affiliation: Associate Professor, Epigenomics Research Program, Department of Native Hawaiian Health, John A. Burns School of Medicine, University of Hawai’i, Mānoa
Date: September 26, 2018
Talk title: Integrative Epigenomic Analyses Support the Early Developmental Origin of Autism Spectrum Disorders.
Abstract: Autism spectrum disorders (ASD) are clinically heterogeneous neurobehavioral diseases suspected to originate in utero when brain cells undergo widespread epigenetic changes to the underlying chromatin landscape, including DNA methylation. Although the normal trajectory of DNA methylation is thought to be critical to transcriptional regulation in neurodevelopment, whether it is compromised in ASD is unknown. Using two complementary genome-wide approaches, we observed significant alterations to DNA methylation in a neural stem cell compartment of postmortem brain from individuals diagnosed with ASD. We found that many of these ASD-specific alterations reside within developmentally regulated chromatin domains, the methylation states of which remarkably resembled that of early fetal brain. Transcriptomic analyses independently demonstrated fetal stage-specific gene expression states in these affected individuals. Together, these findings suggest ASD may arise as a consequence of an “epigenetic delay” in shaping the chromatin landscape during neurodevelopment, providing molecular support of pathological observations implicating its early fetal origins.
Dr. Maunakea received his B.Sc. degree in Biology at Creighton University (2001) and Ph.D. in Biomedical Sciences at the University of California, San Francisco (2008). He completed Postdoctoral training at the National Institutes of Health (2012) and has since joined the John A. Burns School of Medicine at the University of Hawaiʻi, Mānoa. In studying epigenetics for over 15 years, Dr. Maunakea has made several important contributions that have helped advance the field. In particular, he has developed and applied novel high-throughput, genome-wide technologies that survey DNA methylation and histone modifications (Ching et al., 2005; Corley, Zhang, Zheng, Lum-Jones, & Maunakea, 2015; Kraushaar et al., 2013), both central components of epigenetic processes, and has discovered novel roles for DNA methylation in regulating alternative promoter usage (Maunakea, Nagarajan, et al., 2010) and in pre-mRNA splicing (Maunakea, Chepelev, Cui, & Zhao, 2013). In his current position as Associate Professor in the Department of Native Hawaiian Health, Dr. Maunakea is applying epigenomic information toward understanding the mechanistic relationships of gene-environment interactions that underlie the development of diseases of health disparities, including autism and cardiometabolic diseases, anticipating that such studies will contribute to the development of more effective targeted diagnostic, preventative, and therapeutic strategies.