I have two decades of experience in revealing the mechanism underlying diabetes-induced early neural development defects. I also have extensive experience in RNA/DNA methylation, signaling transduction, and cell death pathways. Particularly, we have determined the causative role of kinases including ASK1 and JNK1/2, vascular progenitor exosomes, and cellular organelle stress in diabetes-induced neural tube defects (NTDs) using genetically modified mice. Recently, in a series of investigations, we have elucidated novel epigenetic mechanisms by determining the roles of a group of microRNAs (miRNAs), the ASK1-FoxO3a-caspase 8 pathway in a Science Signaling (2013, Vol 6 Issue 290 ra74), the protein kinase C (PKC)-microRNA129-2-PGC-1and the regulation of acetylation and phosphorylation of a membrane protein in two Nature Communications papers (2017, 8:15182; 2019, 10:282), in diabetic embryopathy. These achievements show my capability in undertaking molecular and epigenetic studies for NTDs induced by maternal or environmental factors. I was trained in reproductive biology, have bridged reproduction to maternal diabetes and diabetic embryopathy, and have experience as both a principal investigator and co-investigator in NIH R01 projects on the effect of maternal hyperglycemia on embryonic development. Over the course of study, I have acquired extensive experience in genetically modified mice including knockouts, transgenic and Cre-Lox recombination, and refined the in vitro whole-embryo culture system. In addition, I have developed methods to accommodate limited sample size of early-stage embryos in gene and protein expression, and kinase activation studies. Based on our strong credential in early neural development and acquired methodology in epigenetic regulations, we are poised to take on the proposed investigation in responding to one NIEHS priority area in epitranscriptomic mechanism underlying environmental factors-induced toxicity and pathogenesis. Drs. Shen, Wang and I have conducted a collaborative study in Northern China, where has the highest NTD rate in the world, by showing the strong association between maternal P-Nitrophenol (PNP) levels and human fetal NTDs. Thus, we hypothesize that alteration of N6-Methyladenosine (m6A) mRNA methylation is responsible for the teratogenicity of the major environmental pollutant PNP leading to NTD formation. I am the founding director of the Center for Birth Defects Research at University of Maryland School of Medicine and a key member of the Center for Studies in Reproduction with a group of investigators working on development in reproductive tissues. Under this excellent environment, I have formed a best team that is most suitable for carrying out the proposed studies. My publication record indicates that I am fully qualified and capable of undertaking the proposed experiments.