Kathy Fange Liu, Ph.D.

Nucleoside-modification Group Lead

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Contact Information

University of Pennsylvania
415 Curie Boulevard
Philadelphia, PA 19104


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Description of Research Expertise

I have a broad background in biochemistry (enzymology), biophysics (biophysical spectroscopy and X-ray crystallography), nucleic acid biology, molecular biology, and cell biology. My laboratory is interested in (1) the mechanisms and consequences of the interplay of multiple RNA modifications in mRNA, tRNA, and rRNA, particularly with regards to their impacts on human disease, and (2) how epitranscriptomics contributes to sex-biased human physiological and pathological processes.

In my Ph.D. study, I carried out biochemical and biophysical characterizations of a human nuclear metalloprotein with previously unknown function and identified its roles in gene expression regulation in a redox-dependent manner. Also, my graduate work on the structure-function relationships of enzymes in the tryptophan-kynurenine pathway facilitated the understanding of the mechanistic enzymology of NAD+ biosynthesis. I developed a wide range of expertise in enzymology and biophysics through the studies of mechanistic enzymology, especially in stopped-flow UV-vis, EPR, and Mössbauer spectroscopic characterizations and time-lapse crystallography snapshots of the catalytic cycle intermediates (determined 40 protein structures and deposited in Protein Data Bank). In my postdoctoral training, I become interested in studying the functions of RNA modifying enzymes and RNA binding proteins in neuronal development and energy metabolism regulation. My major contribution during this period was the identification of the first transfer RNA (tRNA) demethylase enzyme (i.e., an eraser of the modification) and elucidation of an unprecedented translational regulation mechanism through enzyme-mediated tRNA demethylation. This finding, together with the previously identified reversible regulation of mRNA modifications, collectively led to the notion that methyltransferase and demethylase enzymes reversible controls the methylation status of multiple RNA species.

I aim to combine my knowledge of enzymology, biochemistry, spectroscopy, structural biology, and RNA biology to address fundamental research questions that how dysregulation of RNA binding proteins and RNA modifying enzymes contribute to neurological disorders. In addition, my lab has a long interest in the sex-specific features in the physiology and pathology in the neuronal system.

Selected Publications

Hui Shen, Amber Yanas, Michael C. Owens, Celia Zhang, Clark Fritsch, Charlotte M. Fare, Katie E. Copley, James Shorter, Yale E. Goldman, and Kathy Fange Liu: Sexually dimorphic RNA helicases DDX3X and DDX3Y differentially regulate RNA metabolism through phase separation. Mol. Cell 82, 1-16, May 2022.

Shen H, Gonskikh Y, Stoute J, Liu KF.: Human DIMT1 generates N26,6A-dimethylation-containing small RNAs. J. Biol. Chem. 297: 101146, Aug 2021.

Owens MC, Zhang C, Liu KF.: Recent technical advances in the study of nucleic acid modifications. Mol. Cell 81: 4116-4136, Aug 2021.

Shen H, Ontiveros RJ, Owens MC, Liu MY, Ghanty U, Kohli RM, Liu KF.: TET-mediated 5-methylcytosine oxidation in tRNA promotes translation. J. Biol. Chem. 296, 2021.

Stoute J, Liu KF.: CLIP-Seq to identify targets and interactions of RNA binding proteins and RNA modifying enzymes. Methods Enzymol. 658: 419-434, 2021.

Wang, Yifan, Liu, Kathy Fange, Yang, Yu, Davis, Ian, Liu, Aimin: Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens. Proc. Natl. Acad. Sci. U. S. A. 117: 19720-19730, Aug 2020.

Shen, H., Stoute, J., Liu, K. F.: Structural and catalytic roles of the human 18S rRNA methyltransferases DIMT1 in ribosome assembly and translation. J. Biol. Chem. 295(34): 12058-12070, Aug 2020.

Ontiveros, R. Jordan, Shen, Hui, Stoute, Julian, Yanas, Amber, Cui, Yixiao, Zhang, Yuyu, Liu, Kathy Fange: Coordination of mRNA and tRNA methylations by TRMT10A. Proc. Natl. Acad. Sci. U. S. A. 117: 7782-7791, Feb 2020.

Ontiveros, R. Jordan, Stoute, Julian, Liu, Kathy Fange: The chemical diversity of RNA modifications. Biochem. J. 476(8): 1227-1245, Apr 2019.

Yanas A, Liu KF.: RNA modifications and the link to human disease. Methods Enzymol. 626: 133-146, 2019.

Scientific Groups