Description of Research Expertise

The Lin Lab studies RNA modifications (“epitranscriptomics”) in human health and disease. Post-transcriptional RNA processing and modifications are key mechanisms for gene regulation and functional diversity in eukaryotic cells. We develop and apply high-throughput sequencing strategies and transcriptome engineering technologies to study the regulation and function of RNA modifications, including alternative splicing, A-to-I RNA editing, and m6A RNA methylation.

Long-read sequencing technologies are revolutionizing genomic research. These technologies have exciting transcriptomic applications, allowing direct resolution of transcript isoform structures and interrogation of repetitive RNA sequences. Using state-of-the-art nanopore long-read sequencing platform, we develop and apply new strategies to discover and quantify diverse RNA species in bulk tissues and single cells. By comparing the repertoire of full-length RNA transcripts between normal and diseased states (e.g. tumors and rare Mendelian disorders), we hope to discover molecular markers and develop RNA guided diagnostics and therapeutics for these diseases.

RNA editing has emerged as an important and widespread mechanism for generating transcriptome diversity in eukaryotic cells. Aberrant RNA editing has been implicated in a variety of diseases including neurological diseases and cancer. The most abundant type of RNA editing is the A-to-I RNA editing (the deamination of adenosine to inosine) mediated by the ADAR family of RNA editing enzymes. We combine genomic, bioinformatic, and molecular approaches to study the regulation, genetic variation, and function of A-to-I RNA editing, as well as the roles of RNA editing in shaping complex traits and diseases.

N6-methyladenosine (m6A) is an abundant and dynamically regulated class of RNA base modification in mRNAs and non-coding RNAs. It affects multiple aspects of RNA metabolism and controls developmental transitions by regulating mRNA decay and translation. We are developing sensitive sequencing methods to detect RNA m6A methylation in a wider array of clinical and biological samples and using transcriptome engineering technologies to investigate the regulatory and functional consequences of m6A methylation.