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Research
Member, St. Jude Faculty
Director and CEO, St. Jude Children's Research Hospital
Administration
Pharmaceutical Sciences
William Evans, PharmD
Administration
MS 272, Room C-7045K
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: william.evans@stjude.org
Phone: (901) 595-3301
PharmD - University of Tennessee, Memphis
Research in the Evans lab is focused on the pharmacogenomics of anticancer agents, with an emphasis on childhood acute lymphoblastic leukemia (ALL) (reviewed in Evans and Relling, Science 1999; Evans and Relling, Nature, 2004; Pui and Evans, NEJM, 2006; Paugh et al, Curr Opin Ped. 2010). Several approaches are currently being used to identify genes and genome variations that are important determinants of the disposition and effects of antileukemic agents, including the interrogation of candidate genes and the application of genome wide approaches such as gene expression profiling (mRNA, miRNA) of leukemia cells and genomewide SNP analyses (germline and somatic) and genome sequencing of patient cohorts that have been uniformly treated and evaluated on prospective clinical trials at St. Jude Children's Research Hospital (reviewed in Evans and Relling, Nature, 2004). Ongoing studies are investigating genes that the lab has linked with resistance to antileukemic agents (Holleman et al, NEJM, 2004; Lugthart et al, Cancer Cell, 2005), and genes linked to the disposition of antileukemic agents (Kager et al, JCI, 2005; Zaza, Blood, 2005), as well as the influence of somatic and karyotypic abnormalities on genotype-phenotype concordance (Cheng, Nature Genetics, 2005). Work in the lab is funded by an R37 from NCI, a UO1 as part of the NIH-funded Pharmacogenetics Research Network (M. Relling PI), by a Cancer Center Support grant from NCI (R. Gilbertson, PI), and by ALSAC the fundraising organization for St. Jude Children's Research Hospital. The lab comprises a number of post-doctoral fellows, research technologists, scientists, bioinformaticists, computer scientists and students, working with collaborators at St. Jude (including Mary Relling and Ching-Hon Pui as major collaborators, plus additional physicians, clinical pharmacists, research nurses and other staff at St. Jude), and with collaborators at other institutions in the US and Europe. The lab's overall goals are to elucidate genomic determinants of toxicity and efficacy of anticancer agents and translate this knowledge into new diagnostics and treatment strategies to optimize the therapy of ALL (see Relling et al, Lancet Oncol, 2010 ).
Downing JR, Wilson RK, Zhang J, Mardis ER, Pui CH, Ding L, Ley TJ, Evans WE. The pediatric cancer genome project. Nat Genet 44 (6):619-622, 2012. doi: 10.1038/ng.2287. PMID: 22641210
Xu H, Cheng C, Devidas M, Pei D, Fan Y, Yang W, Neale G, Scheet P, Burchard EG, Torgerson DG, Eng C, Dean M, Antillon F, Winick NJ, Martin PL, Willman CL, Camitta BM, Reaman GH, Carroll WL, Loh M, Evans WE, Pui CH, Hunger SP, Relling MV, Yang JJ. ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia. J Clin Oncol Mar 1;30(7):751-7, 2012. Epub 2012 Jan 30. PubMed PMID: 22291082.
Kawedia JD, Liu C, Pei D, Cheng C, Fernandez CA, Howard SC, Campana D, Panetta JC, Bowman WP, Evans WE, Pui CH, Relling MV. Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia. Blood Feb 16;119(7):1658-64, 2012. Epub 2011 Nov 23. PubMed PMID: 22117041.
Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature Jan 11;481(7380):157-63, 2012. doi:10.1038/nature10725. PubMed PMID: 22237106; PubMed Central PMCID: PMC3267575.
Ramsey LB, Bruun GH, Yang W, Treviño LR, Vattathil S, Scheet P, Cheng C, Rosner GL, Giacomini KM, Fan Y, Sparreboom A, Mikkelsen TS, Corydon TJ, Pui CH, Evans WE, Relling MV. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res Jan;22(1):1-8, 2012. Epub 2011 Dec 6. PubMed PMID: 22147369; PubMed Central PMCID: PMC3246196.
Diouf B, Cheng Q, Krynetskaia NF, Yang W, Cheok M, Pei D, Fan Y, Cheng C, Krynetskiy EY, Geng H, Chen S, Thierfelder WE, Mullighan CG, Downing JR, Hsieh P, Pui CH, Relling MV, Evans WE. Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells. Nat Med 17:1298-303, 2011.
Paugh SW, Stocco G, McCorkle JR, Diouf B, Crews KR, Evans WE. Cancer pharmacogenomics. Clin Pharmacol Ther 90:461-6, 2011.
Mikkelsen TS, Sparreboom A, Cheng C, Zhou Y, Boyett JM, Raimondi SC, Panetta JC, Bowman WP, Sandlund JT, Pui CH, Relling MV, Evans WE. Shortening infusion time for high-dose methotrexate alters antileukemic effects: a randomized prospective clinical trial. Journal of Clinical Oncology, May 2011.
Yang JJ, Cheng C, Devidas M, Cao X, Fan Y, Campana D, Yang W, Neale G, Cox NJ, Scheet P, Borowitz MJ, Winick NJ, Martin PL, Willman CL, Bowman WP, Camitta BM, Carroll A, Reaman GH, Carroll WL, Loh M, Hunger SP, Pui CH, Evans WE, Relling MV. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. Nature Genetics, 2011.
Pui CH, Pei D, Campana D, Bowman WP, Sandlund JT, Kaste SC, Ribeiro RC, Rubnitz JE, Coustan-Smith E, Jeha S, Cheng C, Metzger ML, Bhojwani D, Inaba H, Raimondi SC, Onciu M, Howard SC, Leung W, Downing JR, Evans WE, Relling MV. Improved prognosis for older adolescents with acute lymphoblastic leukemia. Journal of Clinical Oncology, 2011.
Kawedia JD, Kaste SC, Pei D, Panetta JC, Cai X, Cheng C, Neale G, Howard SC, Evans WE, Pui CH, Relling MV. Pharmacokinetic, pharmacodynamic and pharmacogenetic determinants of osteonecrosis in children with acute lymphoblastic leukemia. Blood, 2011.
Chen SH, Yang W, Fan Y, Stocco G, Crews KR, Yang JJ, Paugh SW, Pui CH, Evans WE, Relling MV. A genome-wide approach identifies that the aspartate metabolism pathway contributes to asparaginase sensitivity. Leukemia, 2011.
Panetta JC, Sparreboom A, Pui CH, Relling MV, Evans WE. Modeling mechanisms of in vivo variability in methotrexate accumulation and folate pathway inhibition in acute lymphoblastic leukemia cells.PLoS Comput Biol 6(12), 2010.
Chen SH, Pei D, Yang W, Cheng C, Jeha S, Cox NJ, Evans WE, Pui CH, Relling MV. Genetic variations in GRIA1 on chromosome 5q33 related to asparaginase hypersensitivity. Clin Pharmacol Ther 88(2):191-6, 2010.
Relling MV, Altman RB, Goetz MP, Evans WE. Clinical implementation of pharmacogenomics: overcoming genetic exceptionalism. Lancet Oncol 11(6):507-9, 2010.
Yang W, Treviño LR, Yang JJ, Scheet P, Pui CH, Evans WE, Relling MV. ARID5B SNP rs10821936 is associated with risk of childhood acute lymphoblastic leukemia in blacks and contributes to racial differences in leukemia incidence. Leukemia 24(4):894-6, 2010.
Treviño LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D, Chan D, Sparreboom A, Giacomini KM, Pui CH, Evans WE, Relling MV. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 10;27(35):5972-8, 2009.
Treviño LR, Yang W, French D, Hunger SP, Carroll WL, Devidas M, Willman C, Neale G, Downing J, Raimondi SC, Pui CH, Evans WE, Relling MV. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet 41(9):1001-5, 2009.
Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, Ribeiro RC, Rubnitz JE, Raimondi SC, Onciu M, Coustan-Smith E, Kun LE, Jeha S, Cheng C, Howard SC, Simmons V, Bayles A, Metzger ML, Boyett JM, Leung W, Handgretinger R, Downing JR, Evans WE, Relling MV. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med Jun 25;360(26):2730-41, 2009.
Yang JJ, Cheng C, Yang W, Pei D, Cao X, Fan Y, Pounds SB, Neale G, Treviño LR, French D, Campana D, Downing JR, Evans WE, Pui CH, Devidas M, Bowman WP, Camitta BM, Willman CL, Davies SM, Borowitz MJ, Carroll WL, Hunger SP, Relling MV. Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. JAMA 301:393-403, 2009.
Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, Van Zutven LJ, Beverloo HB, Van der Spek PJ, Escherich G, Horstmann MA, Janka-Schaub GE, Kamps WA, Evans WE, Pieters R. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 10:125-34, 2009.
Pottier N, Yang W, Assem M, Panetta JC, Pei D, Paugh SW, Cheng C, Den Boer ML, Relling MV, Pieters R, Evans WE, Cheok MH. The SWI/SNF chromatin-remodeling complex and glucocorticoid resistance in acute lymphoblastic leukemia. J Natl Cancer Inst Dec 17;100(24):1792-803, 2008.
Stocco G, Cheok MH, Crews KR, Dervieux T, French D, Pei D, Yang W, Cheng C, Pui CH, Relling MV, Evans WE. Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther 85:164-72, 2009.
Sorich MJ, Pottier N, Pei D, Yang W, Kager L, Stocco G, Cheng C, Panetta JC, Pui CH, Relling MV, Cheok MH, Evans WE. In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile. PLoS Med Apr 15;5(4):e83, 2008.
Hijiya N, Hudson MM, Lensing S, Zacher M, Onciu M, Behm FG, Razzouk BI, Ribeiro RC, Rubnitz JE, Sandlund JT, Rivera GK, Evans WE, Relling MV, Pui CH. Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA Mar 21;297(11):1207-15, 2007.
Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature Apr 12;446(7137):758-64, 2007.
Jones TS, Yang W, Evans WE, Relling MV. Using HapMap Tools in Pharmacogenomic Discovery: The Thiopurine Methyltransferase Polymorphism. Clin Pharmacol Ther May;81(5):729-34, 2007.
Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, Hijiya N, Rizzari C, Rosner GL, Frudakis T, Pui CH, Evans WE, Relling MV. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood May 15;109(10):4151-7, 2007.
Cheng Q, Cheng C, Crews KR, Ribeiro RC, Pui CH, Relling MV, Evans WE. Epigenetic regulation of human gamma-glutamyl hydrolase activity in acute lymphoblastic leukemia cells. Am J Hum Genet 79(2):264-74, 2006.
Pui CH, Evans WE. Treatment of Acute Lymphoblastic Leukemia. New Eng J Med 354;166-78, 2006.
Cheok MH, Evans WE. Acute lymphoblastic leukemia: a model for the pharmacogenomics of cancer therapy. Nat Rev Cancer 6:117-129, 2006.
For a complete listing view Evans Lab publications via the National Library of Medicine's PubMed.
Last update: August 2012
