We are interested in studying how gene regulatory mechanisms contribute to human diseases including neurodevelopmental disorders. Many genome-wide association studies (GWAS) of diseases have identified the enrichment of non-coding risk variants in regulatory elements such as enhancers, highlighting the contribution of regulatory mechanisms to complex traits. In addition, epigenetic variants, such as cytosine methylation (5mC), have been reported to associate with diseases and can be driven by genetic, environmental or stochastic factors. We are developing and applying new genomic and genetic technologies to address long-standing questions in human diseases including the causal cell type(s) of diseases and the functions of non-coding genetic variants. Two major areas of research in my group are described below.

Developing new epigenomic technologies. Genomic profiling of epigenomic signatures (e.g. DNA methylation, histone modifications) enables the study of gene regulatory events on a global scale. In previous work, we have developed single-cell epigenomic and multi-omic technologies, and use these methods to study the gene regulatory diversity in the brain. We developed a high-throughput single-cell methylome profiling method snmC-seq and its major update snmC-seq2 that have enabled cell-type classification and the identification of cell-type-specific regulatory elements across cortical neuron subtypes in mouse and human (Luo et al., 2017. Science; Luo et al., 2018. Nature Communications). More recently we have developed two single-cell multi-omic methods that allow the multi-modal integration of transcriptome, DNA methylome, chromatin accessibility and chromatin conformation (Luo et al., 2018. bioRxiv; Lee*, Luo*, Zhou* et al., 2019. Nature Methods), providing a near-comprehensive epigenomic characterization of individual brain cells.

Genetic basis of neurodevelopmental disorders. Psychiatric neurodevelopmental disorders such as schizophrenia and autism spectrum disorders (ASD) are highly heritable. Regulatory mechanisms play an important role in both diseases and schizophrenia risk variants are enriched in bulk brain tissue enhancers and immune cell types. Importantly, ASD can be contributed by epigenetic regulation by 5mC. Rett syndrome is a type of ASD and is caused by mutations in MECP2 (methyl-CpG binding protein 2) that recognize 5mC. Neurodevelopmental disorders are likely contributed by multiple cell types in developing and adult brains. We will use a combination of single-cell multi-epigenomics and population genetics approaches to address the contribution of aberrant gene regulations in neurodevelopmental disorders.

Dr. Chongyuan Luo received his B.Sc. degree in Biology (Honors Program in Life Sciences) from China Agricultural University, in 2006. Dr. Luo received his Ph.D. degree in Plant Biology from Rutgers University in 2012. During his Ph.D. study, he studied histone modifications of the model plant species Arabidopsis thaliana using high-throughput sequencing approaches. After completing his postdoctoral training in Joe Ecker’s lab at the Salk Institute for Biological Studies, Dr. Luo joined the Department of Human Genetics at UCLA as an Assistant Professor in 2019.