James R. Downing, MD
James R. Downing, MD

James R. Downing, MD

Member, St. Jude Faculty

  • President and Chief Executive Officer, St. Jude Children's Research Hospital
  • Director, Molecular Pathology Laboratory
  • Donald Pinkel Chair of Childhood Cancer Treatment

Departments

Education

MD – University of Michigan, Ann Arbor (1981)

Honors & Awards

  • 2018 Selected, Marshall Goldsmith’s 100 Coaches Project
  • 2017 E. Donnall Thomas Lecture and Prize from the American Society of Hematology
  • 2017 The Society of Memorial Sloan Kettering Prize 
  • 2016 Elected, American Academy of Arts & Sciences
  • 2016 Appointed, Blue Ribbon Panel for Vice President Joe Biden’s National Cancer Moonshot Initiative
  • 2013 Elected, Institute of Medicine of the National Academy of Sciences (now known as National Academy of Medicine)
  • 2013 Finalist, TIME magazine’s list of the World’s 100 Most Influential People
  • 2012 Association for Molecular Pathology Award for Excellence
  • 2009 American Association for Cancer Research, Team Science Award
  • 2007 The Leukemia & Lymphoma Society's Kenneth B. McCredie Memorial Lecturer
  • 2003 Fellow of American Association for the Advancement of Science (AAAS)
  • 2003 Member, Association of American Physicians
  • 2003 Maude Abbott Lectureship, United States and Canadian Academy of Pathology
  • 1999 Awarded "Alumnus of the Year" University of Michigan, Dearborn
  • 1998 Member, American Society for Clinical Investigation

Research Interests

  • Developmental hematopoiesis and the role of AML1 in the formation of hematopoietic stem cells
  • Mechanisms of Leukemogenesis
  • Mouse genetics
  • Clinical applications of expression profiling

Selected Publications

Wang Z, Liu Q, Wilson CL, Easton J, Mulder H, Chang TC, Rusch MC, Edmonson MN, Rice SV, Ehrhardt MJ, Howell RM, Kesserwan CA, Wu G, Nichols KE, Downing JR, Hudson MM, Zhang J, Yasui Y, Robison LL. Polygenic determinants for subsequent breast cancer risk in survivors of childhood cancer: The St Jude Lifetime Cohort Study (SJLIFE). Clin Cancer Res 24(24)6230-6235, 2018.

Alexander TB, Gu Z, Iacobucci I, Dickerson K, Choi JK, Xu B, Payne-Turner D, Yoshihara H, Loh ML, Horan J, Buldini B, Basso G, Elitzur S, de Haas V, Zwaan CM, Yeoh A, Reinhardt D, Tomizawa D, Kiyokawa N, Lammens T, De Moerloose B, Catchpoole D, Hori H, Moorman A, Moore AS, Hrusak O, Meshinchi S, Orgel E, Devidas M, Borowitz M, Wood B, Heerema NA, Carrol A, Yang YL, Smith MA, Davidsen TM, Hermida LC, Gesuwan P, Marra MA, Ma Y, Mungall AJ, Moore RA, Jones SJM, Valentine M, Janke LJ, Rubnitz JE, Pui CH, Ding L, Liu Y, Zhang J, Nichols KE, Downing JR, Cao X, Shi L, Pounds S, Newman S, Pei D, Guidry Auvil JM, Gerhard DS, Hunger SP, Inaba H, Mullighan CG. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature 562(7727):373-379, 2018.

Wong JC, Bryant V, Lamprecht T, Ma J, Walsh M, Schwartz J, Del Pilar Alzamora M, Mullighan CG, Loh ML, Ribeiro R, Downing JR, Carroll WL, Davis J, Gold S, Rogers PC, Israels S, Yanofsky R, Shannon K, Klco JM. Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes. JCI Insight 3(14), 2018.

Lamba JK, Cao X, Raimondi SC, Rafiee R, Downing JR, Shi L, Gruber T, Ribeiro RC, Rubnitz JE, Pounds SB. Correction,  Integrated epigenetic and genetic analysis identifies markers of prognostic significance in pediatric acute myeloid leukemia. Oncotarget 9(54):30473, 2018.

Stewart E, Federico SM, Chen X, Shelat AA, Bradley C, Gordon B, Karlstrom A, Twarog NR, Clay MR, Bahrami A, Freeman BB 3rd, Xu B, Zhou X, Wu J, Honnell V, Ocarz M, Blankenship K, Dapper J, Mardis ER, Wilson RK, Downing J, Zhang J, Easton J, Pappo A, Dyer MA. Orthotopic patient-derived xenografts of paediatric solid tumours. Nature 549:96-100, 2017. PMCID: PMC5659286 

Faber ZJ, Chen X, Gedman AL, Boggs K, Cheng J, Ma J, Radtke I, Chao JR, Walsh MP, Song G, Andersson AK, Dang J, Dong L, Liu Y, Huether R, Cai Z, Mulder H, Wu G, Edmonson M, Rusch M, Qu C, Li Y, Vadodaria B, Wang J, Hedlund E, Cao X, Yergeau D, Nakitandwe J, Pounds SB, Shurtleff S, Fulton RS, Fulton LL, Easton J, Parganas E, Pui CH, Rubnitz JE, Ding L, Mardis ER, Wilson RK, Gruber TA, Mullighan CG, Schlenk RF, Paschka P, Dohner K, Dohner H, Bullinger L, Zhang J, Klco JM, Downing JR. The genomic landscape of core-binding factor acute myeloid leukemias. Nat Genet 48:1551-1556, 2016. PMCID: PMC5508996

Zhang J, McCastlain K, Yoshihara H, Xu B, Chang Y, Churchman ML, Wu G, Li Y, Wei L, Iacobucci I, Liu Y, Qu C, Wen J, Edmonson M, Payne-Turner D, Kaufmann KB, Takayanagi SI, Wienholds E, Waanders E, Ntziachristos P, Bakogianni S, Wang J, Aifantis I, Roberts KG, Ma J, Song G, Easton J, Mulder HL, Chen X, Newman S, Ma X, Rusch M, Gupta P, Boggs K, Vadodaria B, Dalton J, Liu Y, Valentine ML, Ding L, Lu C, Fulton RS, Fulton L, Tabib Y, Ochoa K, Devidas M, Pei D, Cheng C, Yang J, Evans WE, Relling MV, Pui CH, Jeha S, Harvey RC, Chen IL, Willman CL, Marcucci G, Bloomfield CD, Kohlschmidt J, Mrozek K, Paietta E, Tallman MS, Stock W, Foster MC, Racevskis J, Rowe JM, Luger S, Kornblau SM, Shurtleff SA, Raimondi SC, Mardis ER, Wilson RK, Dick JE, Hunger SP, Loh ML, Downing JR, Mullighan CG. Deregulation of DUX4 and ERG in acute lymphoblastic leukemia. Nat Genet 48:1481-1489, 2016. PMCID: PMC5144107

Zhou X, Edmonson MN, Wilkinson MR, Patel A, Wu G, Liu Y, Li Y, Zhang Z, Rusch MC, Parker M, Becksfort J, Downing JR, Zhang J. Exploring genomic alteration in pediatric cancer using ProteinPaint. Nat Genet 48:4-6, 2016. PMCID: PMC4892362

Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson MR, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Wang S, Weaver MS, Ding L, Mardis ER, Wilson RK, Gajjar A, Ellison DW, Pappo AS, Pui CH, Nichols KE, Downing JR. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med 373:2336-2346, 2015. PMCID: PMC4734119

Andersson AK, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J, Huether R, Kriwacki R, Rusch M, Wu G, Li Y, Mulder H, Raimondi S, Pounds S, Kang G, Shi L, Becksfort J, Gupta P, Payne-Turner D, Vadodaria B, Boggs K, Yergeau D, Manne J, Song G, Edmonson M, Nagahawatte P, Wei L, Cheng C, Pei D, Sutton R, Venn NC, Chetcuti A, Rush A, Catchpoole D, Heldrup J, Fioretos T, Lu C, Ding L, Pui CH, Shurtleff S, Mullighan CG, Mardis ER, Wilson RK, Gruber TA, Zhang J, Downing JR. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nat Genet 47:330-337, 2015. PMCID: PMC4553269

Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46:444-450, 2014. PMCID: PMC4056452

Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs K, Yergeau D, Vadodaria B, Mulder HL, Becksfort J, Gupta P, Huether R, Ma J, Song G, Gajjar A, Merchant T, Boop F, Smith AA, Ding L, Lu C, Ochoa K, Zhao D, Fulton RS, Fulton LL, Mardis ER, Wilson RK, Downing JR, Green DR, Zhang J, Ellison DW, Gilbertson RJ. C11orf95-RELA fusions drive oncogenic NF-kappa B signalling in ependymoma CORRIGENDUM (vol 506, pg 451, 2014). Nature 508:554-, 2014.

Huether R, Dong L, Chen X, Wu G, Parker M, Wei L, Ma J, Edmonson MN, Hedlund EK, Rusch MC, Shurtleff SA, Mulder HL, Boggs K, Vadordaria B, Cheng J, Yergeau D, Song G, Becksfort J, Lemmon G, Weber C, Cai Z, Dang J, Walsh M, Gedman AL, Faber Z, Easton J, Gruber T, Kriwacki RW, Partridge JF, Ding L, Wilson RK, Mardis ER, Mullighan CG, Gilbertson RJ, Baker SJ, Zambetti G, Ellison DW, Zhang J, Downing JR. The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat Commun 5:3630-, 2014. PMCID: PMC4119022

Gruber TA, Larson Gedman A, Zhang J, Koss CS, Marada S, Ta HQ, Chen SC, Su X, Ogden SK, Dang J, Wu G, Gupta V, Andersson AK, Pounds S, Shi L, Easton J, Barbato MI, Mulder HL, Manne J, Wang J, Rusch M, Ranade S, Ganti R, Parker M, Ma J, Radtke I, Ding L, Cazzaniga G, Biondi A, Kornblau SM, Ravandi F, Kantarjian H, Nimer SD, Dohner K, Dohner H, Ley TJ, Ballerini P, Shurtleff S, Tomizawa D, Adachi S, Hayashi Y, Tawa A, Shih LY, Liang DC, Rubnitz JE, Pui CH, Mardis ER, Wilson RK, Downing JR. An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell 22:683-697, 2012. PMCID: PMC3547667

Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, Phoenix TN, Hedlund E, Wei L, Zhu X, Chalhoub N, Baker SJ, Huether R, Kriwacki R, Curley N, Thiruvenkatam R, Wang J, Wu G, Rusch M, Hong X, Becksfort J, Gupta P, Ma J, Easton J, Vadodaria B, Onar-Thomas A, Lin T, Li S, Pounds S, Paugh S, Zhao D, Kawauchi D, Roussel MF, Finkelstein D, Ellison DW, Lau CC, Bouffet E, Hassall T, Gururangan S, Cohn R, Fulton RS, Fulton LL, Dooling DJ, Ochoa K, Gajjar A, Mardis ER, Wilson RK, Downing JR, Zhang J, Gilbertson RJ. Novel mutations target distinct subgroups of medulloblastoma. Nature 488:43-48, 2012. PMCID: PMC3412905

Downing JR, Wilson RK, Zhang J, Mardis ER, Pui CH, Ding L, Ley TJ, Evans WE. The pediatric cancer genome project. Nat Genet 44:619-622, 2012. PMCID: PMC3619412

Cheung NK, Zhang J, Lu C, Parker M, Bahrami A, Tickoo SK , Heguy A, Pappo AS, Federico S, Dalton J, Cheung IY, Ding L, Fulton R, Wang J, Chen X, Becksfort J, Wu J, Billups CA, Ellison D, Mardis ER, Wilson RK, Downing JR, Dyer MA, St Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project . Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA 307:1062-1071, 2012. PMCID: PMC3527076

Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Zhang J, Baker SJ. St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251-253, 2012. PMCID: PMC3288377

Zhang J, Benavente CA, McEvoy J, Flores-Otero J, Ding L, Chen X, Ulyanov A, Wu G, Wilson M, Wang J, Brennan R, Rusch M, Manning AL, Ma J, Easton J, Shurtleff S, Mullighan C, Pounds S, Mukatira S, Gupta P, Neale G, Zhao D, Lu C, Fulton RS, Fulton LL, Hong X, Dooling DJ, Ochoa K, Naeve C, Dyson NJ, Mardis ER, Bahrami A, Ellison D, Wilson RK, Downing JR, Dyer MA. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature 481:329-334, 2012. PMCID: PMC328995

Andersson AK, Miller DW, Lynch JA, Lemoff AS, Cai Z, Pounds SB, Radtke I, Yan B, Schuetz JD, Rubnitz JE, Ribeiro RC, Raimondi SC, Zhang J, Mullighan CG, Shurtleff SA, Schulman BA, Downing JR. IDH1 and IDH2 mutations in pediatric acute leukemia. Leukemia 25:1570-1577, 2011. PMCID: PMC3883450

Mullighan CG, Zhang J, Kasper LH, Lerach S, Payne-Turner D, Phillips LA, Heatley SL, Holmfeldt L, Collins-Underwood JR, Ma J, Buetow KH, Pui CH, Baker SD, Brindle PK, Downing JR. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature 471:235-239, 2011. PMCID: PMC3076610

Mullighan CG, Phillips LA, Su X, Ma J, Miller CB, Shurtleff SA, Downing JR. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 322:1377-1380, 2008. PMCID: PMC2746051

Mullighan CG, Miller CB, Radtke I, Phillips LA, Dalton J, Ma J, White D, Hughes TP, Le Beau MM, Pui CH, Relling MV, Shurtleff SA, Downing JR. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 453:110-114, 2008.

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 446:758-764, 2007.

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature 435:834-838, 2005.

Higuchi M, O'Brien D, Kumaravelu P, Lenny N, Yeoh EJ, Downing JR. Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell 1:63-74, 2002.

Pui CH, Behm FG, Downing JR, Hancock ML, Shurtleff SA, Ribeiro RC, Head DR, Mahmoud HH, Sandlund JT, Furman WL, Roberts WM, Crist WM, Raimondi SC. 11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia. Classic Papers Current Comments 1:95-101, 2000.

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Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES. Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring. Science 286:531-537, 1999.

Fenrick R, Amann JM, Lutterbach B, Wang LL, Westendorf JJ, Downing JR, Hiebert SW. Both TEL and AML-1 contribute repression domains to the t(12;21) fusion protein. Mol Cell Biol 19(10):6566-6574, 1999.

Lowenberg B, Downing JR, Burnett A. Medical progress - Acute myeloid leukemia [Review]. N Engl J Med 341(14):1051-1062, 1999.

McWhirter JR, Neuteboom STC, Wancewicz EV, Monia BP, Downing JR, Murre C. Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia. Proc Natl Acad Sci U S A 96(20):11464-11469, 1999.

Rubnitz JE, Downing JR, Pui CH. Significance of the TEL-AML fusion gene in childhood AML. Leukemia 13(9):1470-1471, 1999.

Downing JR. The AML1-ETO chimaeric transcription factor in acute myeloid leukaemia: biology and clinical significance. Br J Haematol 106(2):296-308, 1999.

Harada H, Harada Y, O'Brien DP, Rice DS, Naeve CW, Downing JR. HERF1, a novel hematopoiesis-specific RING finger protein, is required for terminal differentiation of erythroid cells. Mol Cell Biol 19(5):3808-3815, 1999.

Bodner SM, Naeve CW, Rakestraw KM, Jones BG, Valentine VA, Valentine MB, Luthardt FW, Willman CL, Raimondi SC, Downing JR, Roussel MF, Sherr CJ, Look AT. Cloning and chromosomal localization of the gene encoding human cyclin D-binding Myb-like protein (hDMP1). Gene 229(1-2):223-228, 1999.

Uchida H, Downing JR, Miyazaki Y, Frank R, Zhang J, Nimer SD. Three distinct domains in TEL-AML1 are required for transcriptional repression of the IL-3 promoter. Oncogene 18(4):1015-1022, 1999.

Rubnitz JE, Behm FG, Wichlan D, Ryan C, Sandlund JT, Ribeiro RC, Rivera GK, Hancock ML, Relling MV, Evans WE, Pui CH, Downing JR. Low frequency of TEL-AML1 in relapsed acute lymphoblastic leukemia supports a favorable prognosis for this genetic subgroup. Leukemia 13(1):19-21, 1999.

Rubnitz JE, Pui CH, Downing JR. The role of TEL fusion genes in pediatric leukemias. Leukemia 13(1):6-13, 1999.

Rubnitz JE, Camitta BM, Mahmoud H, Raimondi SC, Carroll AJ, Borowitz MJ, Shuster JJ, Link MP, Pullen DJ, Downing JR, Behm FG, Pui CH. Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation. J Clin Oncol 17(1):191-196, 1999.

Okuda T, Cai Z, Yang S, Lenny N, Lyu C, van Deursen JMA, Harada H, Downing JR. Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. Blood 91:3134-3143, 1998.

Pui C, Rubnitz JE, Hancock ML, Downing JR, Raimondi SC, Rivera GK, Sandlund JT, Ribeiro RC, Head DR, Relling MV, Evans WE, Behm FG. Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. J Clin Oncol 16(12):3768-3773, 1998.

Scurto P, Hsu Rocha M, Kane JR, Williams WK, Haney DM, Conn WP, Shurtleff SA, Downing JR. A multiplex RT-PCR assay for the detection of chimeric transcripts encoded by the risk-stratifying translocations of pediatric acute lymphoblastic leukemia. Leukemia 12(12):1994-2005, 1998.

Westendorf JJ, Yamamato CM, Lenny N, Downing JR, Selsted ME, Hiebert SW. The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-a, inhibits C/EBP-a-dependent transcription, and blocks granulocytic differentiation. Mol Cell Biol 18(1):322-333, 1998.

Rubnitz JE, Downing JR, Crist WM. Pathobiology and clinical significance of molecular genetic findings in childhood tumors. Adv Pediatr 45:315-336, 1998.

Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G, Sherr CJ. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91(5): 649-659, 1997.

Raimondi SC, Shurtleff SA, Downing JR, Rubnitz J, Mathew S, Hancock M, Pui C, Rivera GK, Grosveld GC, Behm FG. 12p abnormalities and the TEL gene (ETV6) in childhood acute lymphoblastic leukemia. Blood 90(11):4559-4566, 1997.

Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84:321-330, 1996.

Hiebert SW, Sun W, Davis JN, Golub T, Shurtleff S, Buijs A, Downing JR, Grosveld G, Roussell MF, Gilliland DG, Lenny N, Meyers S. The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription. Mol Cell Biol 16(4):1349-1355, 1996.

Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML, Chan GC, Pui CH, Grosveld G, Downing JR. TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 9:1985-1989, 1995. 

Parham DM, Shapiro DN, Downing JR, Webber BL, Douglass EC. Solid alveolar rhabdomyosarcomas with the t(2;13). Report of two cases with diagnostic implications. Am J Surg Pathol 18(5):474-478, 1994.

Last update: February 2019