Ben Laufer is a Senior Scientist in the group of Brad Friedman in the department of OMNI Bioinformatics at Genentech. His research examines the interface between gene regulation and neuroscience. He is also the editor for EpiGenie. Outside of the science world he enjoys biking, swimming, and photography.
Postdoctoral Fellowship in Genomics, 2021
University of California Davis, USA
PhD in Cellular & Molecular Biology, 2016
Western University, Canada
BSc (Hons) in Genetics, 2010
Western University, Canada
Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. Ultimately, maternal obesity altered infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic biomarkers.
Polychlorinated biphenyls (PCBs) are developmental neurotoxicants implicated as environmental risk factors for neurodevelopmental disorders (NDD). We examined the effects of prenatal exposure to a human-relevant mixture of PCBs on the DNA methylation profiles of fetal mouse brain and placenta. We found thousands of differentially methylated regions (DMRs) distinguishing placentas and brains from PCB-exposed embryos from sex-matched vehicle controls. In both placenta and brain, PCB-associated DMRs were enriched for functions related to neurodevelopment and cellular signaling and enriched within regions of bivalent chromatin. The placenta and brain PCB DMRs overlapped significantly and mapped to a shared subset of genes enriched for Wnt signaling, Slit/Robo signaling, and genes differentially expressed in NDD models. PBC DMRs also significantly overlapped with DMRs from the brains of humans with Rett syndrome and Dup15q syndrome. These results demonstrate that placenta can be used as a surrogate for embryonic brain DNA methylation changes relevant to an NDD.