Research Interests of the Center for Genomics

There are a few research interests and focuses in the Center for Genomics and Wang Lab.

  1. Genomic and epigenomic mechanisms of maternal e-cigarette (e-cig) smoking-induced abnormal brain development: The overall goal of the study is to investigate the genomic and epigenomic mechanisms underlying abnormal brain development caused by prenatal e-cigarette exposure. Maternal smoking is a well-recognized public health concern associated with increased neurodevelopmental disorders and other health risks in offspring. Substantial evidence indicates various adverse effects of maternal smoking or prenatal nicotine exposure on neonatal brain development, e.g., hyperactivity, reduced cognitive performance, increased anxiety and depression, and increased susceptibility to brain injury. Growing evidence suggests that maternal e-cig use affects brain development, resulting in abnormal cortical neuronal morphology and aberrant neuro-behaviors in offspring. Using a rat prenatal e-cig exposure model and single-nucleus sequencing, we recently found that prenatal e-cig exposure disrupted excitatory-inhibitory (E/I) balance, ratio of excitatory/ inhibitory neurons, in the neonatal brain. E/I balance is crucial for normal brain development and functions, and its disruption has been postulated to underlie the pathogenesis of many neurodevelopmental disorders, including autism spectrum disorders, ADHD, and other psychiatric disorders. However, the underlying genomic and epigenomic mechanisms are still not known. This investigation seeks to fill this knowledge gap. Our hypothesis is that prenatal e-cig exposure induces epigenomic reprogramming and genomic alterations in the developing brain, which cause an E/I imbalance and consequently an increased risk for neurodevelopmental disorders. Exploiting the prenatal e-cig exposure model developed, we intend to achieve three objectives. Aim 1 is to determine the spatial-temporal effects of prenatal e-cig exposure on brain development and progression of E/I imbalance using spatial genomics and single-cell sequencing techniques.  Aim 2 is to determine the epigenomic mechanisms regulating the prenatal e-cig induced E/I imbalance. Aim 3 is to investigate whether prenatal e-cig causes genomic alterations (i.e., SNVs and CNVs) that are involved in E/I imbalance. This project is funded by NIH under the NIDA Animal Genomics Consortium. Many cutting-edge genomic and epigenomic technologies are exploited in our studies, including spatial genomics, single-nucleus RNA-seq and chromatin accessibility (snATAC-seq), and state-of-the-art bioinformatics tools. We expect that this study will provide valuable new insights into the effects of e-cig on the early central nervous system development, which will help explore promising molecular and cellular therapeutic targets for treating e-cig vaping-induced brain damage.
  2. Investigating the underlying epigenomic mechanisms of prenatal Cannabis (THC) exposure-induced abnormal brain development: The overall goal of the study is to investigate the effects of prenatal THC exposure induced abnormal brain development and the underlying epigenomic mechanisms. Marijuana (Cannabis) is one of the most widely used psychotropic drugs in the United States. Cannabis use among pregnant women in the US is increasing with prevalence as high as 14% among 12–18-year-old pregnant women. Accumulating evidence has clearly demonstrated that prenatal exposure to D9- tetrahydrocannabinol (THC), the major psychoactive component of cannabis, has long-term negative effects on decision- making and molecular disturbances linked to synaptic plasticity with profound epigenetic dysregulations that are exacerbated by stress. However, the underlying genomic and epigenomic pathophysiologic mechanisms are still not known. In this study, we investigate whether prenatal THC exposure will lead to altered behavior in rat offspring and impact the intricate connections of neural circuits which may be orchestrated by epigenomic reprogramming in the developing rat brain.  Many cutting-edge genomic and epigenomic technologies are exploited in this study, including spatial transcriptomics, single-nucleus RNA-seq and chromatin accessibility (snATAC-seq), and state-of-the-art bioinformatics tools.
  3. Others: There are many other projects currently supported by the LLU Center for Genomics involving in genomics, epigenomics, single-cell sequencing and bioinformatics in collaborating with many different investigators at LLU, including cancer genomics and clinical genomics.