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STONE, EVERETT M

Everett M Stone

Research Associate Professor, Associate Professor of Oncology
Molecular Biosciences, Department of Oncology


stonesci@utexas.edu

Phone: 512-232-4103

Office Location
MBB

Postal Address
2500 SPEEDWAY
AUSTIN, TX 78712
Everett Stone is a Research Assistant Professor in the Department of Molecular Biosciences at UT Austin where his research efforts focus on the engineering, design, and pharmacological optimization of enzyme therapeutics that can effectively target and degrade small molecule metabolites of importance to diseases caused by inborn errors of metabolism and in cancer. Using directed molecular evolution coupled with high throughput genetic selections and screening strategies his group has successfully engineered several therapeutic enzymes technologies that are currently in clinical trials including an engineered human Arginase for cancer therapy and for treatment of hyperargininemia. Everett is also scientific cofounder of two biopharmaceutical startup companies (Aeglea Biotherapeutics and Kyn Therapeutics) where he serves as consultant in the clinical development of therapeutic enzyme technologies.
  1. Triplett TA, Garrison KC, Marshall N, Donkor M, Blazeck J, Lamb C, Qerqez A, Dekker JD, Tano Y, Wei-Cheng-Lu, Karamitros CS, Ford K, Tan B, Zhang M, McGovern M, Coma S, Kumada Y, Yamany MS, Sentandreu E, Fromm G, Tiziani S, Schreiber TH, Manfredi M, Ehrlich LIR, *Stone E and *Georgiou G. Reversal of IDO-Mediated Cancer Immune Suppression via Systemic Kynurenine Depletion With a Therapeutic Enzyme. 2018 Nature Biotech (In press) (* Corresponding authors)
  1. Poursaitidis I, Wang X, Crighton T, Labuschagne C, Mason D, Cramer SL, Triplett K, Roy R, Pardo OE, Seckl MJ, Rowlinson SW, Stone E, Lamb RF. Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine. Cell Rep. 2017 Mar 14;18(11):2547-2556.
  1. Yan W, *Stone E, *Zhang YJ. Structural Snapshots of an Engineered Cystathionine-γ-lyase Reveal the Critical Role of Electrostatic Interactions in the Active Site. Biochemistry. 2017 Feb 14;56(6):876-885. (* Corresponding authors)
  1. Cramer SL, Saha A, Liu J, Tadi S, Tiziani S, Yan W, Triplett K, Lamb C, Alters SE, Rowlinson S, Zhang YJ, Keating MJ, Huang P, DiGiovanni J, *Georgiou G, *Stone E. Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth. Nat Med. 2017 Jan;23(1):120-127. (* Corresponding authors)
  1. Biswas P, Chavali VR, Agnello G, Stone E, Chakarova C, Duncan JL, Kannabiran C, Homsher M, Bhattacharya SS, Naeem MA, Kimchi A, Sharon D, Iwata T, Riazuddin S, Reddy GB, Hejtmancik JF, Georgiou G, Riazuddin SA, Ayyagari R. A missense mutation in ASRGL1 is involved in causing autosomal recessive retinal degeneration. Hum Mol Genet. 2016 Jun 15;25(12):2483-2497.
  1. Li W, Irani S, Crutchfield A, Hodge K, Matthews W, Patel P, *Zhang YJ, *Stone E. Intramolecular Cleavage of the hASRGL1 Homodimer Occurs in Two Stages. Biochemistry. 2016 Feb 16;55(6):960-9. (* Corresponding authors)
  1. Burrage LC, Sun Q, Elsea SH, Jiang MM, Nagamani SC, Frankel AE, Stone E, Alters SE, Johnson DE, Rowlinson SW, Georgiou G; Members of the Urea Cycle Disorders Consortium, Lee BH. (2015) Human recombinant arginase enzyme reduces plasma arginine in mouse models of arginase deficiency. Hum Mol Genet. Nov 15;24(22):6417-27.
  1. Khoury O, Ghazale N, Stone E, El-Sibai M, Frankel AE, Abi-Habib RJ. (2015) Human recombinant arginase I (Co)-PEG5000 [HuArgI (Co)-PEG5000]-induced arginine depletion is selectively cytotoxic to human glioblastoma cells. J Neurooncol. Mar;122(1):75-85.
  1. Chrysostomou C, Quandt EM, Marshall NM, Stone E, Georgiou G. (2015) An alternate pathway of arsenate resistance in E. coli mediated by the glutathione S-transferase GstB. ACS Chem Biol. Mar 20;10(3):875-82.
  1. Agrawal, V., Meininger,C.J., Frenkel,E.P., Woo,J.H., Mauldin, J.P., Stone, E.M., Jo,C., Kleypas, K. and Frankel, A.E. (2014) In vivo evaluation of human recombinant Co-arginase against A375 melanoma; Melanoma Research. Dec;24(6):556-67.
  1. Tanios R, Bekdash A, Kassab E, Stone E, Georgiou G, Frankel AE, Abi-Habib RJ. (2013) Human recombinant arginase I (Co)-PEG5000 [HuArgI(Co)-PEG5000]-induced arginine depletion is selectively cytotoxic to human acute myeloid leukemia cells. Leuk Res. Nov;37(11):1565-71.
  1. Agnello G., Chang L, Lamb C., *Georgiou G. and *Stone E. (2013) Discovery of a Substrate Selectivity Motif in Amino Acid Decarboxylases Unveils a Taurine Biosynthesis Pathway in Prokaryotes, ACS Chemical Biology Oct 18;8(10):2264-71. (* Corresponding authors)
  1. Paley O, Agnello G, Cantor J, Yoo TH,*Georgiou G,*Stone E. (2013) GFP reporter screens for the engineering of amino acid degrading enzymes from libraries expressed in bacteria. Methods Mol Biol. 2013;978:31-44. (* Corresponding authors)
  1. Stone, E., Paley, O., Hu, J., Ekerdt, B., Cheung, N. K., and Georgiou, G. (2012) De novo Engineering of a Human Cysathionine-γ-Lyase for Systemic L-Met Depletion Cancer Therapy, ACS Chemical Biology.
  1. *Romero, P. A., *Stone, E., Lamb, C., Chantranupong, L., Krause, A., Miklos, A. E., Hughes, R. A., Fechtel, B., Ellington, A. D., and Arnold, F. H. (2012) SCHEMA-Designed Variants of Human Arginase I and II Reveal Sequence Elements Important to Stability and Catalysis, ACS Synthetic Biology 1, 221-228.(* Equal authors)
  1. Mauldin, J. P., Zeinali, I., Kleypas, K., Woo, J. H., Blackwood, R. S., Jo, C. H., Stone, E. M., Georgiou, G., and Frankel, A. E. (2012) Recombinant Human Arginase Toxicity in Mice Is Reduced by Citrulline Supplementation, Translational Oncology 5, 26.
  1. Li, W., Cantor, J. R., Yogesha, S., Yang, S., Chantranupong, L., Qingxia Liu, J., Agnello, G., Georgiou, G., *Stone, E. M., and *Zhang, Y. (2012) Uncoupling Intramolecular Processing and Substrate Hydrolysis in the N-terminal Nucleophile Hydrolase hASRGL1 by Circular Permutation, ACS Chemical Biology. (* Corresponding authors)
  1. Cantor, J. R., Panayiotou, V., Agnello, G., *Georgiou, G., and *Stone, E. M. (2012) Engineering reduced-immunogenicity enzymes for amino acid depletion therapy in cancer, Protein Engineering for Therapeutics 502, 291. (* Corresponding authors)
  1. 15. Agrawal, V., Woo, J. H., Mauldin, J. P., Jo, C., Stone, E. M., Georgiou, G., and Frankel, A. E. (2012) Cytotoxicity of human recombinant arginase I (Co)-PEG5000 in the presence of supplemental L-citrulline is dependent on decreased argininosuccinate synthetase expression in human cells, Anti-Cancer Drugs 23, 51.
  1. 14. Agrawal, V., Alpini, S. E. J., Stone, E. M., Frenkel, E. P., and Frankel, A. E. (2012) Targeting methionine auxotrophy in cancer: discovery & exploration, Expert opinion on biological therapy 12, 53-61.
  1. Stone, E., Chantranupong, L., Gonzalez, C., O'Neal, J., Rani, M., VanDenBerg, C., and Georgiou, G.(2011) Strategies for optimizing the serum persistence of engineered human Arginase I for cancer therapy, Journal of Controlled Release.
  1. 12. Glazer, E. S., Stone, E. M., Zhu, C., Massey, K. L., Hamir, A. N., and Curley, S. A. (2011) Bioengineered human arginase I with enhanced activity and stability controls hepatocellular and pancreatic carcinoma xenografts, Translational oncology 4, 138.
  1. *Cantor, J. R., *Stone, E. M., and Georgiou, G. (2011) Expression and Biochemical Characterization of the Human Enzyme N-Terminal Asparagine Amidohydrolase (hNTAN1), Biochemistry 50, 3025. (* Equal authors)
  1. Stone, E. M., Glazer, E. S., Chantranupong, L., Cherukuri, P., Breece, R. M., Tierney, D. L., Curley, S. A., Iverson, B. L., and Georgiou, G. (2010) Replacing Mn2+ with Co2+ in human arginase I enhances cytotoxicity toward l-arginine auxotrophic cancer cell lines, ACS chemical biology 5, 333-342.
  1. Stone, E. M., Chantranupong, L., and Georgiou, G. (2010) The second-shell metal ligands of human arginase affect coordination of the nucleophile and substrate, Biochemistry 49, 10582.
  1. Cantor, J. R., Stone, E. M., Chantranupong, L., and Georgiou, G. (2009) The Human Asparaginase-like Protein 1 hASRGL1 Is an Ntn Hydrolase with β-Aspartyl Peptidase Activity, Biochemistry 48, 11026-11031.
  1. Linsky, T. W., Monzingo, A. F., Stone, E. M., Robertus, J. D., and Fast, W. (2008) Promiscuous partitioning of a covalent intermediate common in the pentein superfamily, Chemistry & Biology 15, 467-475.
  1. Stone, E. M., Costello, A. L., Tierney, D. L., and Fast, W. (2006) Substrate-assisted cysteinedeprotonation in the mechanism of dimethylargininase (DDAH) from Pseudomonas aeruginosa, Biochemistry 45, 5618-5630.
  1. Thomas, P. W., Stone, E. M., Costello, A. L., Tierney, D. L., and Fast, W. (2005) The quorumquenching lactonase from Bacillus thuringiensis is a metalloprotein, Biochemistry 44, 7559-7569.
  1. Stone, E. M., Schaller, T. H., Bianchi, H., Person, M. D., and Fast, W. (2005) Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase, Biochemistry 44, 13744-13752.
  1. Stone, E. M., Person, M.D., Costello, N. J., and Fast, W. (2005) Characterization of a transient covalent adduct formed during dimethylarginine dimethylaminohydrolase catalysis, Biochemistry 44, 7069-7078.
  1. Stone, E. M., and Fast, W. (2005) A continuous spectrophotometric assay for dimethylarginine dimethylaminohydrolase, Analytical Biochemistry 343, 335.
  1. Liu, D., Lepore, B. W., Petsko, G. A., Thomas, P. W., Stone, E. M., Fast, W., and Ringe, D. (2005) Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis, PNAS 102, 11882-11887.

2017 Emerging Inventor of the year, UT Austin

Chemical Biology

Drugs, Drug Discovery & Diagnostics

Enzymology