Trainee Paper Spotlight: Yong Lei

Trainee Author: Yong Lei, PhD
Postdoctoral Associate Fellow, Stem Cells & Regenerative Medicine Centre, Baylor College of Medicine (BCM), Houston, Texas
(Photo courtesy Lei)

Lei, Y. et al. Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein. Nat. Commun. 8, 16026 doi: 10.1038/ncomms16026 (2017).

Yong Lei and colleagues report a new engineered tool fusion protein, dCas9-MQ1 DNA methyltransferase, and demonstrate that rapid and specifically targeted CpG methylation can be achieved in both human cells and mouse embryos.

Using a highly active prokaryotic DNA methyltransferase, they demonstrate the utility of this protein through methylation at CTCF sites and at imprinted loci in mice zygotes. This study introduces a highly useful tool fusion protein that will allow for the elucidation of the effects of DNA methylation at particular loci and how certain DNA methylation marks impact both wild-type and disease-related protein interactions with the genome.

ASHG: Could you describe your research for us?

Dr. Lei: My research focuses on the deterioration of the DNA methylation maintenance system in human. Additionally, I am studying the genetic changes at non-coding regions, e.g., promoters, using CRISPR-mediated saturated mutagenesis screen in human disease models.

ASHG: What are your career goals?

Dr. Lei: Non-coding variants play significant roles in the alteration of binding affinity of key transcription factors, DNA methylation writer, histone modifiers, and chromosome structure proteins. These alterations dysregulate transcription and eventually result in diseases. My goal is to become an independent scientist focusing on understanding the roles of genetic variations at the noncoding regions in human diseases.

ASHG: Why did you choose genetics as your field of study?

Dr. Lei: Although transcriptome can be epigenetically shaped via environmental changes or nutritional choices, phenotypic expression remains largely determined by genetics. Moreover, increasing studies demonstrate that DNA sequence itself may be the central factor that governs epigenetic status at regulatory elements in human genome. I chose genetics as the field of study because I believe genetics plays the determining role in the generation of human diseases.

ASHG: If you could pick three words that describe yourself, what would they be?

Dr. Lei: Curious, keen, multi-potentiality.

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