Kathy Fange Liu, Ph.D

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Associate Professor of Biochemistry and Biophysics
Member, Institute for Diabetes, Obesity, and Metabolism
Member, The Penn Institute for Regenerative Medicine
Member, Pennsylvania Muscle Institute
Group Leader, Penn Institute for RNA Innovation
Full Member, Abramson Family Cancer Research Institute
Leadership Council, Penn Center for Genome Integrity
Department: Biochemistry and Biophysics

Contact information
Department of Biochemistry & Biophysics
University of Pennsylvania Perelman School of Medicine
347-A Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6059 USA
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 Distinction)
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 regard 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 functions 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 the 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 reversibly control 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 of cancer.

Selected Publications

Maldonado-Lopez A, Huang S, Pacella G, Ko EK, Shen H, Stoute J, Sinkfield M, Anderson A, Prouty S, Li H, Seykora JT, Liu Kathy Fange, and Capell B: METTL3 maintains epithelial homeostasis through m6A-dependent regulation of chromatin modifiers. Sci. Adv. 9(35), Sep 2023 Notes: My lab contributed to quantifying the levels of m6A using mass spec and analyzing the molecular pathways m6A might be involved in epithelial homeostasis.

Gonskikh Y, Stoute J, Shen H, Budinich K, Pingul B, Schultz K, Elashal H, Marmorstein R, Shi J, Liu Kathy Fange: Non-catalytic regulation of 18S rRNA methyltransferase DIMT1 in acute myeloid leukemia. Genes & Dev. 1;37(7-8):321-335, April 2023.

Liu Kathy Fange: The condensates underlying sexual dimorphism. Mol. Cell 83(7): 1016-1021, April 2023.

She H, Owens MC, Yanas A, Lavorando E, Tang HY, Liu Kathy Fange: Mutant forms of DDX3X with diminished catalysis form hollow condensates that exhibit sex-specific regulation. BioRxiv March 2023.

Perlegos A, Shields E, Shen H, Liu Kathy Fange, and Bonini N: Mettl3-dependent m6A modification attenuates the brain stress response in Drosophila. Nat. Commun. 13(5387), Oct 2022 Notes: My lab contributed to quantifying m6A level changes using the mass spec and analyzing the pathways m6A involved in heat shock response.

Basavappa M; Ferretti M; Dittmar M; Stoute J; Sullivan M; Whig K; Shen H; Liu Kathy Fange; Schultz D; Beiting D; Lynch K; Henao-Mejia J; Cherry S: The novel lncRNA ALPHA specifically targets chikungunya virus to control infection. Mol. Cell 82(19): 3729-3744.e10, Oct 2022 Notes: My lab contributed to performing polysome profiling experiments to analyze the impacts of lncRNA ALPHA on translation.

Owens MC, Liu Kathy Fange: TRIBE-STAMP reveals new insights into the functions of RNA binding proteins. Genes Dev 36: 954-955, Sep 2022.

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(14): 2588-2603, May 2022.

Shen H, Ontiveros RJ, Owens MC, Liu MY, Ghanty U, Kohli RM, Liu Kathy Fange: TET-mediated 5-methylcytosine oxidation in tRNA promotes translation. J. Biol. Chem. 296: 100087, Nov 2021.

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

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Last updated: 07/16/2024
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