John D. York, Ph.D.

Professor

john.york@vanderbilt.edu
Faculty Appointments
Chair of the Department of Biochemistry Professor of Biochemistry Natalie Overall Warren Chair in Biochemistry
Education
Ph.D., Molecular Cell Biology & Biochemistry, Washington University, Saint Louis, MissouriB.S., University of Iowa, Iowa City, Iowa
Office Address
Department of Biochemistry
Vanderbilt University Medical Center
607 Light Hall
Nashville, TN 37232-0146
Research Description
The York laboratory studies cellular signaling networks and we have defined an evolutionarily conserved intracellular code required for the proper adaptation of cells and development of organisms. We define this collectively as an inositol phosphate (IP) code, and our work has helped to understand fundamental basic science questions in biology related to how cells enhance signaling specificity through generation of diverse chemical messengers. Recently our studies of a structurally conserved family of Lithium-inhibited enzymes, including inositol phosphatases, has led us to define a role for sulfur assimilation pathways in the regulation of bone formation, iron transport, and protein translation. We observe that defects in compartment specific sulfur assimilation pathways lead to disease states including: chondrodysplasia (dwarfism), anasarca (whole-body edema), and iron-deficiency anemia.
Research Keywords
Cell Signaling, Signal Transduction, Lithium, Manic Depression, Bipolar disorder, Inositol, Inositide, Lipid, Metabolism, Structural Biology, Anemia, Chondrodysplasia
Publications
Hatch AJ, Odom AR, York JD. Inositol phosphate multikinase dependent transcriptional control. Adv Biol Regul [print-electronic]. 2017 May; 64: 9-19. PMID: 28342784, PII: S2212-4926(16)30064-1, DOI: 10.1016/j.jbior.2017.03.001, ISSN: 2212-4934.

Hargrove TY, Friggeri L, Wawrzak Z, Qi A, Hoekstra WJ, Schotzinger RJ, York JD, Guengerich FP, Lepesheva GI. Structural analyses of Candida albicans sterol 14a-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis. J. Biol. Chem [print-electronic]. 2017 Apr 4/21/2017; 292(16): 6728-43. PMID: 28258218, PMCID: PMC5399120, PII: M117.778308, DOI: 10.1074/jbc.M117.778308, ISSN: 1083-351X.

Seeds AM, Tsui MM, Sunu C, Spana EP, York JD. Inositol phosphate kinase 2 is required for imaginal disc development in Drosophila. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Dec 12/22/2015; 112(51): 15660-5. PMID: 26647185, PMCID: PMC4697392, PII: 1514684112, DOI: 10.1073/pnas.1514684112, ISSN: 1091-6490.

Emptage RP, Tonthat NK, York JD, Schumacher MA, Zhou P. Structural basis of lipid binding for the membrane-embedded tetraacyldisaccharide-1-phosphate 4'-kinase LpxK. J. Biol. Chem [print-electronic]. 2014 Aug 8/29/2014; 289(35): 24059-68. PMID: 25023290, PMCID: PMC4148839, PII: M114.589986, DOI: 10.1074/jbc.M114.589986, ISSN: 1083-351X.

Pulloor NK, Nair S, McCaffrey K, Kostic AD, Bist P, Weaver JD, Riley AM, Tyagi R, Uchil PD, York JD, Snyder SH, GarcĂ­a-Sastre A, Potter BV, Lin R, Shears SB, Xavier RJ, Krishnan MN. Human genome-wide RNAi screen identifies an essential role for inositol pyrophosphates in Type-I interferon response. PLoS Pathog. 2014 Feb; 10(2): e1003981. PMID: 24586175, PMCID: PMC3937324, PII: PPATHOGENS-D-13-02234, DOI: 10.1371/journal.ppat.1003981, ISSN: 1553-7374.

Hudson BH, York JD. Tissue-specific regulation of 3'-nucleotide hydrolysis and nucleolar architecture. Adv Biol Regul [print-electronic]. 2014 Jan; 54: 208-13. PMID: 24309248, PMCID: PMC3926666, PII: S2212-4926(13)00093-6, DOI: 10.1016/j.jbior.2013.11.002, ISSN: 2212-4934.

Hudson BH, Frederick JP, Drake LY, Megosh LC, Irving RP, York JD. Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Mar 3/26/2013; 110(13): 5040-5. PMID: 23479625, PMCID: PMC3612647, PII: 1205001110, DOI: 10.1073/pnas.1205001110, ISSN: 1091-6490.

Endo-Streeter S, Tsui MK, Odom AR, Block J, York JD. Structural studies and protein engineering of inositol phosphate multikinase. J. Biol. Chem [print-electronic]. 2012 Oct 10/12/2012; 287(42): 35360-9. PMID: 22896696, PMCID: PMC3471723, PII: M112.365031, DOI: 10.1074/jbc.M112.365031, ISSN: 1083-351X.

Hudson BH, York JD. Roles for nucleotide phosphatases in sulfate assimilation and skeletal disease. Adv Biol Regul. 2012 Jan; 52(1): 229-38. PMID: 22100882, PMCID: PMC3845023, PII: S0065-2571(11)00072-0, DOI: 10.1016/j.advenzreg.2011.11.002, ISSN: 2212-4934.

Hatch AJ, York JD. SnapShot: Inositol phosphates. Cell. 2010 Dec 12/10/2010; 143(6): 1030-1030.e1. PMID: 21145466, PMCID: PMC4299573, PII: S0092-8674(10)01367-X, DOI: 10.1016/j.cell.2010.11.045, ISSN: 1097-4172.

Monserrate JP, York JD. Inositol phosphate synthesis and the nuclear processes they affect. Curr. Opin. Cell Biol [print-electronic]. 2010 Jun; 22(3): 365-73. PMID: 20359876, PII: S0955-0674(10)00030-X, DOI: 10.1016/j.ceb.2010.03.006, ISSN: 1879-0410.

Frederick JP, Tafari AT, Wu SM, Megosh LC, Chiou ST, Irving RP, York JD. A role for a lithium-inhibited Golgi nucleotidase in skeletal development and sulfation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Aug 8/19/2008; 105(33): 11605-12. PMID: 18695242, PMCID: PMC2575314, PII: 0801182105, DOI: 10.1073/pnas.0801182105, ISSN: 1091-6490.

Fridy PC, Otto JC, Dollins DE, York JD. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J. Biol. Chem [print-electronic]. 2007 Oct 10/19/2007; 282(42): 30754-62. PMID: 17690096, PII: M704656200, DOI: 10.1074/jbc.M704656200, ISSN: 0021-9258.

Otto JC, Kelly P, Chiou ST, York JD. Alterations in an inositol phosphate code through synergistic activation of a G protein and inositol phosphate kinases. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Oct 10/2/2007; 104(40): 15653-8. PMID: 17895383, PMCID: PMC1994134, PII: 0705729104, DOI: 10.1073/pnas.0705729104, ISSN: 0027-8424.

Lee YS, Mulugu S, York JD, O'Shea EK. Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science. 2007 Apr 4/6/2007; 316(5821): 109-12. PMID: 17412959, PMCID: PMC2211727, PII: 316/5821/109, DOI: 10.1126/science.1139080, ISSN: 1095-9203.

Mulugu S, Bai W, Fridy PC, Bastidas RJ, Otto JC, Dollins DE, Haystead TA, Ribeiro AA, York JD. A conserved family of enzymes that phosphorylate inositol hexakisphosphate. Science. 2007 Apr 4/6/2007; 316(5821): 106-9. PMID: 17412958, PII: 316/5821/106, DOI: 10.1126/science.1139099, ISSN: 1095-9203.

Frederick JP, Mattiske D, Wofford JA, Megosh LC, Drake LY, Chiou ST, Hogan BL, York JD. An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Jun 6/14/2005; 102(24): 8454-9. PMID: 15939867, PMCID: PMC1150869, PII: 0503706102, DOI: 10.1073/pnas.0503706102, ISSN: 0027-8424.

York SJ, Armbruster BN, Greenwell P, Petes TD, York JD. Inositol diphosphate signaling regulates telomere length. J. Biol. Chem [print-electronic]. 2005 Feb 2/11/2005; 280(6): 4264-9. PMID: 15561716, PII: M412070200, DOI: 10.1074/jbc.M412070200, ISSN: 0021-9258.

Odom AR, Stahlberg A, Wente SR, York JD. A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science. 2000 Mar 3/17/2000; 287(5460): 2026-9. PMID: 10720331, PII: 8365, ISSN: 0036-8075.

York JD, Odom AR, Murphy R, Ives EB, Wente SR. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science. 1999 Jul 7/2/1999; 285(5424): 96-100. PMID: 10390371, PII: 7646, ISSN: 0036-8075.

Guo S, Stolz LE, Lemrow SM, York JD. SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. J. Biol. Chem. 1999 May 5/7/1999; 274(19): 12990-5. PMID: 10224048, ISSN: 0021-9258.