James R. Downing, MD

James R. Downing, MD

Member, St. Jude Faculty
Scientific Director, St. Jude Children's Research Hospital
Associate Director of Basic Research, Cancer Center
Co-Leader, Hematological Malignancies Program
Director, Molecular Pathology Laboratory

Departments

Administration
Pathology

Contact Information

James Downing, MD
Administration
MS271, Room C-7045M
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: james.downing@stjude.org
Phone: (901) 595-3956
FAX: (901) 595-3749

Education

MD - University of Michigan, Ann Arbor (1981)


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

The AML1/CBF beta transcription factor complex in normal and leukemic hematopoiesis


Selected Publications

Mullighan CG, Miller CB, Radtke I, Philips LA, Dalton J, Ma J, White D, Hughes TP, Le Beau MM, Pui, C-H, Relling MV, Shurtleff SA, Downing JR. BCR-ABL1 lymphoblastic leukemia is characterized by the deletion of Ikaros. Nature 2008 (in press).

Mullighan CG, Kennedy A, Zhou X, Radtke I, Phillips LA, Shurtleff SA, Downing JR. Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias. Leukemia 21: 2000-9, 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 S, Downing JR. Genome wide analysis of genetic alterations in acute lymphoblastic leukemia. Nature 446:758-64, 2007.

Flotho C, Coustan-Smith E, Pei D, Iwamoto S, Song G, Cheng C, Pui CH, Downing JR, Campana D. Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2. Blood 108:1050-1057, 2006.

Lu J, Getz G, Miska EA, Lamb J, Alverez-Saavedra EA, Sweet-Cordero A, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub T. MicroRNA expression profiles classify human cancers. Nature 435:834-8, 2005.

Ross ME, Mahfouz R, Onciu M, Liu H-C, Zhou X, Song G, Shurtleff SA, Pounds S, Cheng C, Ma J, Ribeiro RC, Rubnitz JE, Girtman K, Williams WK, Raimondi SC, Liang D-C, Shih L-Y, Pui C-H, Downing JR. Gene expression profiling of pediatric acute myelogenous leukemia. Blood 104:3679-3687, 2004.

Lorsbach RB, Moore J, Ang SO, Sun W, Lenny N, Downing JR. Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression. Blood 103:2522-2529, 2004.

Pui CH, Relling MV, Downing JR. Mechanisms of Disease: Acute Lymphoblastic Leukemia. New Engl J Med 350: 1535-1548, 2004.

Sun W, Downing JR. Haploinsufficiency of AML1 results in a decrease in the number of LTR-HSCs, while simultaneously inducing an increase in more mature progenitors. Blood 104: 3565-3572, 2004.

Ross ME, Xiaodong Z, Song G, Shurtleff SA, Girtman K, Williams WK, Liu HC, Mahfouz R, Raimondi SC, Lenny N, Patel A, Downing JR. Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood 102:2951-2959, 2003.

Downing JR, Shannon KM. Acute leukemia. A pediatric perspective. Cancer Cell 2: 437-45, 2002.

Yeoh E, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Jinyan L, Liu H, Pui CH, Evans WE, Naeve C, Wong L, Downing JR. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1: 133-143, 2002.

Higuchi H, O’Brien D, Kumaravelu P, Lenny N, Yeoh E-J, 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.

Cai Z, de Bruijn M, Ma X, Dortland B, Luteijn T, Downing JR, Dzierzak E. Haploinsuffiency of AML1 affects the temporal and spatial generation of hematopoietic stem cells in the mouse embryo. Immunity 12: 423-431, 2000.

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.

Okuda T, Cai Z, Yang S, Lenny N, Lyu C-j, van Deursen J, 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.

Rubnitz JE, Downing JR, Pui C-H, Shurtleff SA, Raimondi SC, Evans WE, Head DR, Crist WM, Rivera GK, Hancock ML, Boyett JM, Buijs A, Grosveld and Behm FG. TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J of Clin Onc 15: 1150-1157, 1997.

Kamijo T, Zindy F, Roussel M, Quelle DE, Downing JR, Ashmun RA, Grosveld G, and Sherr CJ. Tumor Suppression at the mouse INK4a locus mediated by the alternative reading frame produce p19ARF. Cell 91: 649-659, 1997.

Okuda T, Deursen JV, Hiebert SW, Grosveld G, Downing JR. AML-1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84: 321-330, 1996.

Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML, Pui C-H, 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.

Okuda T, Shurtleff SA, Valentine MB, Raimondi SC, Head DR, Behm F, Curcio-Brint AM, Liu Q, Pui C-H, Sherr CJ, Beach D, Look AT, Downing JR. Frequent deletion of p16INK4a/MTS1 and p15INK4b/MTS2 in pediatric lymphoblastic leukemia. Blood 85: 2321-2330, 1995.

Last update: April 2008

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