Faculty

Kathy Fange Liu, Ph.D

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Assistant Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics

Contact information
347-B Clinical Research Building
415 Curie Boulevard
University of Pennsylvania
Philadelphia, PA 19104
Office: 215-573-6413
Lab: 215-573-6414
Education:
B.S. (Cell Biology with Honors)
Capital Normal University, Beijing, P.R. China, 2008.
Ph.D (Biochemistry with Distiction)
Georgia State University, USA, 2013.
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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

Ontiveros, R. Jordan, Shen, Hui, Stoute, Julian, Yanas, Amber, Cui, Yixiao, Zhang, Yuyu, Liu, Kathy Fange: Coordination of mRNA and tRNA methylations by TRMT10A. Proceedings of the National Academy of Sciences of the United States of America 117: 7782-7791, 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, 2020.

Wang, Yifan, Liu, Kathy Fange, Yang, Yu, Davis, Ian, Liu, Aimin: Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens. Proceedings of the National Academy of Sciences of the United States of America 117: 19720-19730, 2020.

Hui Shen1, Robert Jordan Ontiveros, Michael C. Owens, Monica Yun Liu, Uday Ghanty, Rahul M. Kohli, Kathy Fange Liu: TET-mediated 5-methylcytosine oxidation in tRNA promotes translation. J. Bio. Chem. accepted, 2020.

Shen H, Liu KF* : Characterization of Tet2-regulated demethylation of 5-methylcytosine in messenger RNA Nat. Common. Under 2nd revision 2020.

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

Wei Jiangbo, Liu Fange, Lu Zhike, Fei Qili, Ai Yuxi, He P Cody, Shi Hailing, Cui Xiaolong, Su Rui, Klungland Arne, Jia Guifang, Chen Jianjun, He Chuan: Differential mA, mA, and mA Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm. Molecular cell 71(6): 973-985.e5, Sep 2018.

Yang Yu, Liu Fange, Liu Aimin: Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities. The Journal of biological chemistry 293(27): 10415-10424, 07 2018.

Liu Fange, He Chuan: A new modification for mammalian messenger RNA. The Journal of biological chemistry 292(35): 14704-14705, 09 2017.

Ferreira Patrick, Shin Inchul, Sosova Iveta, Dornevil Kednerlin, Jain Shailly, Dewey Deborah, Liu Fange, Liu Aimin: Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency. Molecular genetics and metabolism 120(4): 317-324, 04 2017.

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Last updated: 11/14/2020
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