Jiyeon Choi Appointed as Earl Stadtman Tenure-Track Investigator
In summer 2019, Jiyeon Choi, Ph.D., M.S., was appointed Earl Stadtman tenure-track investigator in the Laboratory of Translational Genomics (LTG). Her research focuses on identifying susceptibility genes and functional variants in lung cancer and melanoma and investigating their role in tumorigenesis and contribution to increased risk. Dr. Choi joined DCEG in 2011 as a postdoctoral fellow, was promoted to research fellow in 2016, and was selected for the NIH Distinguished Scholars Program in 2019.
As a postdoctoral fellow under Kevin Brown, Ph.D., Dr. Choi integrated epidemiology and cancer biology by conducting research in melanoma post-genome wide association studies (GWAS). She led a transition from a gene-by-gene strategy to a multi-locus/genome-scale approach, in part by adopting a high-throughput functional screening system called massively parallel reporter assay (MPRA). MPRA rapidly assesses the gene-regulatory potential of thousands of genetic variants that may contribute to the development of cancer. She also created one of the first melanocyte-specific multi-quantitative-trait-locus (multi-QTL) datasets to characterize key mechanisms of cancer-associated functional variants, such as heritable regulation of lineage-specific gene expression, splicing, non-coding RNA expression, and DNA methylation. By integrating these genomic approaches, she was able to shorten the amount of time needed to process GWAS data and, in turn, quickly identified the most plausible candidate genes and variants from known melanoma GWAS loci—an approach that holds great promise for the field of cancer genetics. Using this approach, she identified Chr21q22.3 (MX2) as a candidate gene, which she then associated with a tumor-accelerating phenotype in an animal model. Advancing these findings even further, she explored the mechanism of how PARP1 on Chr1q42.1, a susceptibility gene, contributes to the development of melanoma in the context of oncogenic driver mutations by regulating cell-type specific pathways. Finally, she has identified rare germline variants from familial melanoma cases via sequencing efforts.
With this impressive background in melanoma susceptibility, Dr. Choi will extend and broaden this approach as she applies it to lung cancer, the leading cause of cancer death. While the most well-known determinant is tobacco smoking, only a small fraction of smokers develops lung cancer, and 10-25% of lung malignancies arise in never-smokers, suggesting the possibility of other environmental factors and a genetic component. “In genetic studies of lung cancer, however,” Dr. Choi explains, “many susceptibility genes and variants remain unidentified, and a functional understanding of how known variants influence risk is lacking.”
Dr. Choi’s research program will fill this gap by investigating the functional basis of genetic susceptibility to lung cancer and further evaluating the potential interaction of susceptibility gene function with environmental exposures. She will apply high-throughput approaches, including MPRA, CRISPR screening, and chromatin interaction studies, in order to quickly prioritize targetable genes and variants from multiple lung cancer GWAS loci. She is also establishing and analyzing cell-type specific QTL resources to improve understanding of the role of lineage-specific gene expression in genetic susceptibility to lung cancer.
Finally, Dr. Choi will characterize GWAS loci in lung cancer among never smokers and functionally validate data generated from the Sherlock-lung study, which aims to trace lung cancer etiology in this population. This effort includes cell-based assessment of exogenous and endogenous tumor mutational processes inferred from somatic mutational signatures and characterization of somatic driver events specific to lung cancer in never smokers. Dr. Choi will integrate findings from these studies to identify the cellular and environmental context in which susceptibility genes operate and confer risk.
Named after Earl Stadtman, a noted biochemist at the National Heart, Lung, and Blood Institute, the Stadtman program is a trans-NIH recruitment initiative designed to attract the most talented early-career scientists to NIH.