Jin Ye, Ph.D.

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Jin Ye received a MS degree in Biochemistry from Case Western Reserve University in 1995. He was mentored by Nobel laureates Michael Brown and Joseph Goldstein at UT Southwestern, obtaining his PhD in Cell Regulation in 2000, and continuing in a postdoctoral fellowship from 2000 to 2004.He joined the faculty at the UT Southwestern Medical Center in 2004 as an Assistant Professor. He was promoted to Professor in 2022.

Dr. Ye’s research interests are to understand lipid-mediated signaling. Currently his lab is investigating how lipid-mediated signaling affects cancer progression. His group has recently uncovered that doxorubicin, an extensively-used chemotherapeutic reagent, stimulates production of a class of lipid called ceramide, which in turn inhibits proliferation of cancer cells through proteolytic activation of a transcription factor called CREB3L1. Unlike a typical transcription factor, CREB3L1 is synthesized as an inactive transmembrane precursor. Ceramide stimulates proteolysis of CREB3L1 so that the N-terminal domain of the protein can reach nucleus to active genes that block progression of the cell cycle. His lab further demonstrates that ceramide induces cleavage of CREB3L1 by inverting the membrane topology of a transmembrane protein called TM4SF20, turning it from an inhibitor to an activator of CREB3L1 cleavage. This novel mechanism, which has been designated by his group as “Regulated Alternative Translocation”, appears to be crucial for ceramide-mediated signaling. In addition to ceramide, his group is also interested in the roles of abnormal cholesterol and fatty acid metabolism on progression of kidney cancers. He is currently appointed as a full member of the graduate faculty in the Biological Chemistry and Integrated Biology Program.

Graduate School

Case Western Reserve Univ (1995), Biochemistry

Graduate School

Univ of Tx Southwestern Med Ct (2000), Cell Regulation

• Lipid-mediated signaling in cancer development and treatment
• Regulation of lipid metabolism

Featured Publications

Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence.

Wang J, Han S, Ye J, Cell Rep 2023 Mar 42 4 112311

FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids.

Cui S, Simmons G, Vale G, Deng Y, Kim J, Kim H, Zhang R, McDonald JG, Ye J, Proc Natl Acad Sci U S A 2022 Apr 119 17 e2107189119

Identification of TRAMs as Sphingolipid-Binding Proteins Using a Photoactivatable and Clickable Short Chain Ceramide Analog.

Deng Y, You L, Lu Y, Han S, Wang J, Vicas N, Chen C, Ye J, J Biol Chem 2021 Nov 101415

Regulating G protein-coupled receptors by topological inversion.

Denard B, Han S, Kim J, Ross EM, Ye J, Elife 2019 Mar 8

Identification of residues critical for topology inversion of the transmembrane protein TM4SF20 through regulated alternative translocation.

Wang J, Kinch LN, Denard B, Lee CE, Esmaeilzadeh Gharehdaghi E, Grishin N, Ye J J. Biol. Chem. 2019 Feb

Inverting the Topology of a Transmembrane Protein by Regulating the Translocation of the First Transmembrane Helix.

Chen Q, Denard B, Lee CE, Han S, Ye JS, Ye J Mol. Cell 2016 Aug 63 4 567-78

Unsaturated Fatty Acids Stimulate Tumor Growth through Stabilization of β-Catenin.

Kim H, Rodriguez-Navas C, Kollipara RK, Kapur P, Pedrosa I, Brugarolas J, Kittler R, Ye J Cell Rep 2015 Oct 13 3 495-503

UAS Domain of Ubxd8 and FAF1 Polymerizes upon Interaction with Long Chain Unsaturated Fatty Acids.

Kim H, Zhang H, Meng D, Russell G, Lee JN, Ye J J. Lipid Res. 2013 May

Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1.

Denard B, Lee C, Ye J Elife 2012 1 e00090

Identification of Ubxd8 protein as a sensor for unsaturated fatty acids and regulator of triglyceride synthesis.

Lee JN, Kim H, Yao H, Chen Y, Weng K, Ye J, Proc Natl Acad Sci U S A 2010 Dec 107 50 21424-9

 Featured Books

Regulated Intramembrane Proteolysis. In Encyclopedia of Biological Chemistry, 2nd edition

Jin Ye (2013). Oxford, United Kingdom, Elsevier Inc.

Regulation of Cholesterol and Fatty Acid Metabolism. In Discoveries in Modern Science: Exploration, Invention, Technology

Jin Ye (2015). Farmington Hills, MI, Gale

• Department of Molecular Genetics (2004)
• Simmons Comprehensive Cancer Center (2016)