William Evans, PharmD

William E. Evans, PharmD

Member, St. Jude Faculty
Endowed Chair in Pharmacogenomics

Departments

Pharmaceutical Sciences

Contact Information

William Evans, PharmD
Pharmaceutical Sciences
MS 313, Room I-5108
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: william.evans@stjude.org
Phone: (901) 595-6850

Education

PharmD - University of Tennessee, Memphis


Research Interests

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, Clin Pharmacol Ther 2011). 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 use of genome wide approaches such as gene expression profiling (mRNA, microRNA) of leukemia cells, genome-wide SNP analyses (germline and somatic) and whole exome/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), or by our collaborators in the COG and in Europe (eg, Princess Maxima Center, Utrecht). 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 (Kager et al, JCI 2005; Zaza, Blood 2005) or pharmacologic targets (Diouf et al, JAMA 2015; Paugh et al, Nat Genet 2015) of antileukemic agents as well as the influence of somatic and karyotypic abnormalities on genotype-phenotype concordance (Cheng, Nature Genetics 2005; Diouf et al, Nature Med 2011). Work in the lab is funded by a long-standing R37 from NCI (CA36401, W Evans PI), a UO1 as part of the NIH-funded Pharmacogenetics Research Network (GM92666, M. Relling PI), by a Cancer Center Support grant from NCI (CA21765R. Gilbertson, PI), and by ALSAC, the fundraising organization for St. Jude Children's Research Hospital. The lab comprises a number of post-doctoral fellows, staff scientists, research technologists, bioinformaticists, computational scientists and students, working with collaborators at St. Jude (including Mary Relling, Ching-Hon Pui, Charles Mullighan, Hiroto Inaba, Kirsten Ness, and Jun Yang 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 (HudsonAlpha, University of Chicago) and Europe (Erasmus University, Princess Maxima Center). 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; Paugh et al, Clin Pharm Ther 2011; Dunnenberger et al, Ann Rev Pharmacol Tox 2015).

Evans Research Lab


Selected Publications

Paugh SW, Bonten, EJ, Savic D, Ramsey LB, Thierfelder WE, Gurung P, Malireddi RK, Actis M, Mayasundari A, Min J, Coss DR, Laudermilk LT, Panetta JC, McCorkle JR, FanY, Crews KR, Stocco G, Wilkinson MR, Ferreira AM, Cheng C, Yang W, Karol SE, Fernandez CA, Diouf B, Smith C, Hicks JK, Zanut A, Giordanengo A, Crona D, Bianchi JJ, Holmfeldt L, Mullighan CG, den Boer ML, Pieters R, Jeha S, Dunwell TL, Latif F, Bhojwani D, Carroll WL, Pui CH, Myers RM, Guy RK, Kanneganti TD, Relling MV, Evans WE. NALP3 inflammasome up-regulation and CASP1 cleavage of the glucocorticoid receptor causes glucocorticoid resistance in leukemia cells. Nat Genet 2015. Epub ahead of print. doi:10.1038/ng.3283. PMID: 25938942.

Diouf B, Crews KR, Lew G, Pei D, Cheng C, Bao J, Zheng JJ, Yang W, Fan Y, Wheeler HE, Wing C, Delaney SM, Komatsu M, Paugh SW, McCorkle JR, Lu X, Winick NJ, Carroll WL, Loh ML, Hunger SP, Devidas M, Pui CH, Dolan ME, Relling MV, Evans WE. Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA 313(8):815-23, 2015. doi: 10.1001/jama.2015.0894. PMID: 25710658.

Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay N, Wong FL, Evans WE, Pui CH, Bhatia S, Relling MV. Inherited NUDT15 Variant Is a Genetic Determinant of Mercaptopurine Intolerance in Children With Acute Lymphoblastic Leukemia. J Clin Oncol Jan 26, 2015. Epub ahead of print. pii: JCO.2014.59.4671. PMID: 25624441.

Perez-Andreu V, Roberts KG, Xu H, Smith C, Zhang H, Yang W, Harvey RC, Payne-Turner D, Devidas M, Cheng IM, Carroll WL, Heerema NA, Carroll AJ, Raetz EA, Gastier-Foster JM, Marcucci G, Bloomfield CD, Mrózek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Rowe JM, Luger SM, Tallman MS, Dean M, Burchard EG, Torgerson DG, Yue F, Wang Y, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Loh ML, Willman CL, Hunger SP, Mullighan CG, Yang JJ. A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults. Blood 125(4):680-6, 2015. doi: 10.1182/blood-2014-09-595744. PMID: 25468567.

Dunnenberger HM, Crews KR, Hoffman JM, Caudle KE, Broeckel U, Howard SC, Hunkler RJ, Klein TE, Evans WE, Relling MV. Preemptive Clinical Pharmacogenetics Implementation: Current Programs in Five United States Medical Centers. Annu Rev Pharmacol Toxicol Oct 2, 2014. PMID: 25292429.

Ramsey LB, Janke LJ, Edick MJ, Cheng C, Williams RT, Sherr CJ, Evans WE, Relling MV. Host thiopurine methyltransferase status affects mercaptopurine antileukemic effectiveness in a murine model. Pharmacogenet Genomics 24(5):263-71, 2014. doi: 10.1097/FPC.0000000000000044. PMID: 24710003.

Perez-Andreu V, Roberts KG, Harvey RC, Yang W, Cheng C, Pei D, Xu H, Gastier-Foster J, E S, Lim JY, Chen IM, Fan Y, Devidas M, Borowitz MJ, Smith C, Neale G, Burchard EG, Torgerson DG, Klussmann FA, Villagran CR, Winick NJ, Camitta BM, Raetz E, Wood B, Yue F, Carroll WL, Larsen E, Bowman WP, Loh ML, Dean M, Bhojwani D, Pui CH, Evans WE, Relling MV, Hunger SP, Willman CL, Mullighan CG, Yang JJ. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nat Genet 45(12):1494-8, 2013. doi: 10.1038/ng.2803. PMID: 24141364.

Pui CH, Evans WE. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol 50(3):185-96, 2013. doi: 10.1053/j.seminhematol.2013.06.007. PMID: 23953334. PMCID: PMC3771494.

Xu H, Yang W, Perez-Andreu V, Devidas M, Fan Y, Cheng C, Pei D, Scheet P, Burchard EG, Eng C, Huntsman S, Torgerson DG, Dean M, Winick NJ, Martin PL, Camitta BM, Bowman WP, Willman CL, Carroll WL, Mullighan CG, Bhojwani D, Hunger SP, Pui CH, Evans WE, Relling MV, Loh ML, Yang JJ. Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations. J Natl Cancer Inst May 15;105(10):733-42, 2013. doi: 10.1093/jnci/djt042. Epub 2013 Mar 19. PMID: 23512250

Evans WE, Crews KR, Pui CH. A Health-Care System Perspective on Implementing Genomic Medicine: Pediatric Acute Lymphoblastic Leukemia as a Paradigm. Clin Pharmacol Ther Jan 17, 2013. doi: 10.1038/clpt.2013.9. [Epub ahead of print] PMID: 23462885

Meyer JA, Wang J, Hogan LE, Yang JJ, Dandekar S, Patel JP, Tang Z, Zumbo P, Li S, Zavadil J, Levine RL, Cardozo T, Hunger SP, Raetz EA, Evans WE, Morrison DJ, Mason CE, Carroll WL. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet Mar;45(3):290-4, 2013. doi: 10.1038/ng.2558. Epub 2013 Feb 3. PMID: 23462885

Ramsey LB, Panetta JC, Smith C, Yang W, Fan Y, Winick NJ, Martin PL, Cheng C, Devidas M, Pui CH, Evans WE, Hunger SP, Loh M, Relling MV. Genome-wide study of methotrexate clearance replicates SLCO1B1. Blood Feb 7;121(6):898-904. doi: 10.1182/blood-2012-08-452839. Epub 2012 Dec 11. PMID: 23233662

Hunger SP, Baruchel A, Biondi A, Evans WE, Jeha S, Loh M, Moericke A, Pieters R, Relling MV, Schmiegelow K, Schrappe M, Silverman LB, Stanulla M, Valsecchi MG, Vora A, Pui CH. The thirteenth international childhood acute lymphoblastic leukemia workshop report: La Jolla, CA, USA, December 7-9, 2011. Pediatr Blood Cancer Feb;60(2):344-8, 2013. doi: 10.1002/pbc.24354. Epub 2012 Sep 28. PMID: 23024117

Yang JJ, Cheng C, Devidas M, Cao X, Campana D, Yang W, Fan Y, Neale G, Cox N, Scheet P, Borowitz MJ, Winick NJ, Martin PL, Bowman WP, Camitta B, Reaman GH, Carroll WL, Willman CL, Hunger SP, Evans WE, Pui CH, Loh M, Relling MV. Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia. Blood Nov 15;120(20):4197-204, 2012. doi: 10.1182/blood-2012-07-440107. Epub 2012 Sep 24. PMID: 23007406

Hicks JK, Crews KR, Hoffman JM, Kornegay NM, Wilkinson MR, Lorier R, Stoddard A, Yang W, Smith C, Fernandez CA, Cross SJ, Haidar C, Baker DK, Howard SC, Evans WE, Broeckel U, Relling MV. A clinician-driven automated system for integration of pharmacogenetic interpretations into an electronic medical record. Clin Pharmacol Ther Nov;92(5):563-6, 2012. doi: 10.1038/clpt.2012.140. Epub 2012 Sep 19. PMID: 22990750

Crews KR, Hicks JK, Pui CH, Relling MV, Evans WE. Pharmacogenomics and individualized medicine: translating science into practice. Clin Pharmacol Ther Oct;92(4):467-75, 2012. doi: 10.1038/clpt.2012.120. Epub 2012 Sep 5. PMID: 22948889

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.

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.

For a complete listing view Evans Lab publications via the National Library of Medicine's PubMed.


Last update: July 2013