Yunsun Nam
University of Texas Southwestern Medical Center, TX·Biochemistry
Cells tune which genes are active in part by chemically marking their RNA, the working copies of genes. They also use small regulatory RNAs.
- Fields
Biochemistry
Pharmacology
Biophysics
- Topics
epitranscriptome
RNA modification
m6A
- Grants
- 2 known grants, through Mar 2031
What they work on
- Determine how heavy metals alter the efficiency and specificity of METTL3-METTL14, the enzyme that adds m6A marks to mRNA, and how metal-driven m6A changes link to chromatin and DNA methylation.
- Test how different metals affect METTL1, a cancer-promoting tRNA methyltransferase, including crosstalk with other tRNA modifications and AKT kinase signaling that phosphorylates METTL1.
- Uncover how heavy metals dysregulate microRNA biogenesis by the metal-dependent Drosha-DGCR8 complex, and how this interacts with RNA methylation.
- Screen a large chemical library with a high-throughput assay for small molecules that block METTL3/METTL14 activity, prioritizing a gain-of-function mutant.
- Confirm top hits with orthogonal biochemical, biophysical and cell-based assays for specificity over other m6A methyltransferases, and begin structure-guided lead optimization.
More about the research
Together these RNA marks are called the epitranscriptome. When enzymes that make these marks go wrong, cancer can follow. Two projects center on RNA-modifying enzymes linked to cancer. One asks how toxic heavy metals disrupt these enzymes. The other seeks drug-like molecules that switch off one of them.
Why it matters
Heavy metal exposure and faulty RNA modification are both linked to cancer. Learning how carcinogenic metals derail RNA-modifying enzymes could clarify how environmental exposures lead to disease. Inhibitors of METTL3/METTL14 could become lead compounds for cancers driven by this enzyme's overactivity. They would also be tool compounds for dissecting m6A biology in cancer research.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kexin Xu
University of Virginia, VA·Biochemistry
Examine how the m6A-adding enzyme METTL3 binds the nuclear pore protein NUP93 to speed export of m6A-marked mRNAs, using single-molecule microscopy and epitranscriptome-editing tools.
Thomas G Boyer
University of Texas Health Science Center at San Antonio, TX·Biochemistry
Determine how fibroid-causing MED12 mutations destabilize the T-loop of the CDK8 enzyme and reduce its substrate binding and activity, using structural biology and biochemistry.
Senthil Kumar Radhakrishnan
Virginia Commonwealth University, VA·Biochemistry
Express and purify DDI2 protease and run high-throughput screens with a protein thermal shift assay, which detects binding by shifts in protein unfolding temperature, to find small molecules that bind DDI2.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
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