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About

Dr. R. Keith Humphries, MD, PhD
Director, Terry Fox Laboratory


Research Interest

  • Genetic control and manipulation of normal and malignant hemopoiesis
  • Stem cell regulation, retroviral gene transfer, transgenic mice

My research concentrates on two major areas. The first is the characterization of genes that underlie the self-renewal and multipotential differentiation capacity of hemopoietic stem cells. The former property is essential for the life long maintenance of hemopoietic function and for regeneration after damage or transplantation; the latter results in the production of the multiple specialized but short lived mature blood cell types.

Most recently, we have focused on the Hox homeobox family of transcription factors as candidate intrinsic regulators of normal primitive hematopoietic cell properties and as participants in leukemic transformation. Expression profiling has documented differential expression of Hox genes in primitive hematopoietic subpopulations and retroviral gene transfer has been used to engineer the overexpression of Hox genes with observed marked effects on hemopoiesis in mouse transplantation and embryonic stem cell models. These studies have revealed remarkable Hox gene specific effects ranging from the ability of HOXB4 to markedly enhance stem cell self-renewal to a leukemogenic activity of other Hox genes. These findings implicate Hox genes and likely upstream regulators of Hox gene expression, downstream targets of Hox genes and interacting proteins in the regulation of normal stem cell self-renewal/differentiation and in leukemic transformation. Work now is directed at better understanding this regulatory gene network in both murine and human hematopoietic cells. This includes further functional studies using genetic engineering in bone marrow, transgenic animals and embryonic stem cells; expression profiling to identify possible target genes; and yeast-2 hybrid analyses to identify novel interacting proteins.

The second major line of investigation is directed towards the development of improved gene transfer methods to primitive hematopoietic stem cells with the goal of improving approaches for gene function studies and gene therapy. This work includes a major emphasis on developing strategies for gene therapy of inherited anemias such as Thalassemia and sickle cell disease. This work includes testing of a variety of novel retro- and lentiviral based vectors carrying potentially therapeutic genes in a variety of in vitro and in vivo models - the latter including transgenic mice that mimic human Thalassemia or sickle cell disease. Novel approaches for non-viral mediated gene transfer to hemopoietic cells are also being explored by utilizing cre/lox recombination methodology.

Publications

Xiang P, Lo C, Argiropoulos B, Lai CB, Rouhi A, Imren S, Jiang X, Mager D & Humphries RK. Identification of E74-like factor 1 (ELF1) as a transcriptional regulator of the Hox co-factor MEIS1. Exp Hematol. 2010 Jun 23 [Epub ahead of print]. View Abstract

Eaves CJ & Humphries RK. Acute myeloid leukemia and the Wnt pathway. N Engl J Med 362: 2326-2327, 2010. View PubMed Link

Heuser M & Humphries RK. Biologic and experimental variation of measured cancer stem cells. Cell Cycle 9: 909-12, 2010. View Abstract

Argiropoulos B, Yung E, xiang P, Lo CY, Kuchenbauer F, Palmqvist L, Reindl C, Heuser M, Sekulovic S, Rosten P, Muranyi A, Goh SL, Featherstone M & Humphries RK. Linkage of the potent leukemogenic activity of Meis1 to cell cycle entry and transcriptional regulation of cyclin D3. Blood 115: 4071-82, 2010. View Abstract

Heuser M, Park G, Moon Y, Berg T, Xiang P, Kuchenbauer F, Vollett S, Lai C & Humphries RK. Extrinsic signals determine myeloid-erythroid lineage switch in MN1 leukemia. Exp Hematol 38:174-9, 2010. View Abstract

Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Fuchenbauer F, Yap D, Humphries RK, Griffith OL, Shah S, Zhu H, Kimbara M, Shashkin P, Charlot JF, Tcherpakov M, Corbett R, Tam A, Varhol R, Smailus D, Moksa M, Zhao Y, Delaney A, Qian H, Birol I, Schein J, Moore R, Holt R, Horsman DE, Connors JM, Jones S, Aparicio S, Hirst M, Gascoyne RD, & Marra MA. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 42:181-5, 2010. View Abstract

Fisher CL, Pineault N, Brookes C, Helgason CD, Ohta H, Bodner C, Hess JL, Humphries RK & Brock HW. Loss-of-function additional sex combs-like1 mutations disrupt hematopoiesis but do not cause severe myelodysplasia or leukemia.  Blood 115: 38-46, 2010. View Abstract

Fisher CL, Lee I, Bloyer S, Bozza S, Chevalier J, Dahl A, Bodner C, Helgason CD, Hess JL, Humphries RK & Brock HW. Additional sex combs-like 1 belongs to the enhancer of trithorax and polycomb group and genetically interacts with Cbx2 in mice.  Dev Biol 337: 9-15, 2010. View Abstract

Starczynowski DT, Kuchenbauer F, Argiropoulos B, Sung S, Morin R, Muranyi A, Hirst M, Hogge D, Marra M, Wells RA, Buckstein R, Lam W, Humphries RK & Karsan A. Identification of miR-145 and miR-146a as mediators of the 5q-syndrome phenotype.  Nat Med 16: 49-58, 2010. View Abstract

Reindl C, Quentmeier H, Petropoulos K, Greif PA, Benthaus T, Argiropoulos B, Mellert G, Vempati S, Duyster J, Buske C, Bohlander SK, Humphries KR, Hiddemann W & Spiekermann K. CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes.  Clin Cancer Res 15: 2238-2247, 2009. View Abstract

Heuser M, Yap DB, Leung M, de Algara TR, Tafech A, McKinney S, Dixon J, Thresher R, Colledge B, Carlton M, Humphries RK, & Aparicio SA. Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood 113 (7): 1432-43, 2009. View Abstract

Heuser M, Sly LM, Argiropoulos B, Kuchenbauer F, Lai C, Weng A, Leung M, Lin G, Brookes C, Fung S, Valk PJ, Delwel R, Lowenberg B, Krystal G, & Humphries RK. Modelling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal. Blood, 2009. View Abstract

Heuser M, Kuchenbauer F, Argiropoulos B, Sekulovic S, Leung M, Stasiak M, Ganser A, & Humphries RK. Priming reloaded? Blood 114 (4): 925-6; author reply 926-7, 2009. View Abstract

Sekulovic S, Imren S & Humphries K. High level in vitro expansion of murine hematopoietic stem cells. In:Current Protocols in Stem Cell Biology. John Wiley & Sons Inc.,NJ., p Unit 2A.7., 2008. View Abstract

Faubert A, Chagraoui J, Mayotte N, Fréchette M, Iscove NN, Humphries RK & Sauvageau G. Complementary and independent function for Hoxb4 and Bmi1 in HSC activity. Cold Spring Harb Symp Quant Biol 2008. View Abstract

Heuser M*, Yap D*, Leung M, de Algara TR, Tafech A, McKinney S, Dixon J, Thresher R, Colledge B, Carlton M, Humphries RK** & Aparicio S**. Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function and extreme sensitivity to DNA demethylation. Blood 2008 (*authors contributed equally to this study; **co-senior authors). View Abstract

Kuchenbauer F*, Morin RD*, Argiropoulos B, Petriv OI, Griffith M, Heuser M, Yung E, Piper J, Delaney A, Prabhu A-L, Zhao Y, McDonald H, Zeng T, Hirst M, Hansen CL, Marra MA & Humphries RK. In-depth characterization of the microRNA transcriptome in a leukemia progression model .Genome Res 18: 1787-97, 2008. (*authors contributed equally to this study). View Abstract

Argiropoulos B, Palmqvist L, Yung E, Kuchenbauer F, Heuser M, Sly LM, Wan A, Krystal G, & Humphries RK. Linkage of Meis1 leukemogenic activity to multiple downstream effectors including Trib2 and Ccl3. Exp Hematol 36 (7): 845-59, 2008. View Abstract

Hirose K, Abramovich C, Argiropoulos B, & Humphries RK. Leukemogenic properties of NUP98-PMX1 are linked to NUP98 and homeodomain sequence functions but not to binding properties of PMX1 to serum response factor. Oncogene, 2008. View Abstract

Rouhi A, Mager DL, Humphries RK, & Kuchenbauer F. MiRNAs, epigenetics, and cancer. Mamm Genome, 2008. View Abstract

Zhang XB, Beard BC, Trobridge GD, Wood BL, Sale GE, Sud R, Humphries RK, & Kiem HP. High incidence of leukemia in large animals after stem cell gene therapy with a HOXB4-expressing retroviral vector. J Clin Invest 118 (4): 1502-10, 2008. View Abstract

Argiropoulos B, & Humphries RK. Hox genes in hematopoiesis and leukemogenesis. Oncogene 26 (47): 6766-76, 2007. View Abstract

Argiropoulos B, Yung E, & Humphries RK. Unraveling the crucial roles of Meis1 in leukemogenesis and normal hematopoiesis. Genes Dev 21 (22): 2845-9, 2007. View Abstract

Cellot S, Krosl J, Chagraoui J, Meloche S, Humphries RK, & Sauvageau G. Sustained in vitro trigger of self-renewal divisions in Hoxb4hiPbx1(10) hematopoietic stem cells. Exp Hematol 35 (5): 802-16, 2007. View Abstract

Heuser M, Argiropoulos B, Kuchenbauer F, Yung E, Piper J, Fung S, Schlenk RF, Dohner K, Hinrichsen T, Rudolph C, Schambach A, Baum C, Schlegelberger B, Dohner H, Ganser A, & Humphries RK. MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML. Blood 110 (5): 1639-47, 2007. View Abstract

Lu M, Glover CH, Tien AH, Humphries RK, Piret JM, & Helgason CD. Involvement of tyrosine kinase signaling in maintaining murine embryonic stem cell functionality. Exp Hematol 35 (8): 1293-302, 2007. View Abstract

Ohta H, Sekulovic S, Bakovic S, Eaves CJ, Pineault N, Gasparetto M, Smith C, Sauvageau G, & Humphries RK. Near-maximal expansions of hematopoietic stem cells in culture using NUP98-HOX fusions. Exp Hematol 35 (5): 817-30, 2007. View Abstract

Palmqvist L, Pineault N, Wasslavik C, & Humphries RK. Candidate genes for expansion and transformation of hematopoietic stem cells by NUP98-HOX fusion genes. PLoS ONE 2 (1): e768, 2007. View Abstract

Zhang XB, Schwartz JL, Humphries RK, & Kiem HP. Effects of HOXB4 overexpression on ex vivo expansion and immortalization of hematopoietic cells from different species. Stem Cells 25 (8): 2074-81, 2007. View Abstract

Deshpande AJ, Cusan M, Rawat VP, Reuter H, Krause A, Pott C, Quintanilla-Martinez L, Kakadia P, Kuchenbauer F, Ahmed F, Delabesse E, Hahn M, Lichter P, Kneba M, Hiddemann W, Macintyre E, Mecucci C, Ludwig WD, Humphries RK, Bohlander SK, Feuring-Buske M, & Buske C. Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia. Cancer Cell 10 (5): 363-74, 2006. View Abstract

Fisher CL, Randazzo F, Humphries RK, & Brock HW. Characterization of Asxl1, a murine homolog of Additional sex combs, and analysis of the Asx-like gene family. Gene 369: 109-18, 2006. View Abstract

Gurevich RM, Rosten PM, Schwieger M, Stocking C, & Humphries RK. Retroviral integration site analysis identifies ICSBP as a collaborating tumor suppressor gene in NUP98-TOP1-induced leukemia. Exp Hematol 34 (9): 1192-201, 2006. View Abstract

Palmqvist L, Argiropoulos B, Pineault N, Abramovich C, Sly LM, Krystal G, Wan A, & Humphries RK. The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia. Blood 108 (3): 1030-6, 2006. View Abstract

Zhang XB, Beard BC, Beebe K, Storer B, Humphries RK, & Kiem HP. Differential effects of HOXB4 on nonhuman primate short- and long-term repopulating cells. PLoS Med 3 (5): e173, 2006. View Abstract

Abramovich C, & Humphries RK. Hox regulation of normal and leukemic hematopoietic stem cells. Curr Opin Hematol 12 (3): 210-6, 2005. View Abstract

Abramovich C, Pineault N, Ohta H, & Humphries RK. Hox genes: from leukemia to hematopoietic stem cell expansion. Ann N Y Acad Sci 1044: 109-16, 2005. View Abstract

Ferrell CM, Dorsam ST, Ohta H, Humphries RK, Derynck MK, Haqq C, Largman C, & Lawrence HJ. Activation of stem-cell specific genes by HOXA9 and HOXA10 homeodomain proteins in CD34+ human cord blood cells. Stem Cells 23 (5): 644-55, 2005. View Abstract

Lawrence HJ, Christensen J, Fong S, Hu YL, Weissman I, Sauvageau G, Humphries RK, & Largman C. Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells. Blood 106 (12): 3988-94, 2005. View Abstract

Milsom MD, Duxbury R, Gagen D, Humphries RK, Schmidt M, von-Kalle C, & Fairbairn LJ. Overexpression of HOXB4 confers a myelo-erythroid differentiation delay in vitro. Leukemia 19 (1): 148-53, 2005. View Abstract

Palmqvist L, Glover CH, Hsu L, Lu M, Bossen B, Piret JM, Humphries RK, & Helgason CD. Correlation of murine embryonic stem cell gene expression profiles with functional measures of pluripotency. Stem Cells 23 (5): 663-80, 2005. View Abstract

Pineault N, Abramovich C, & Humphries RK. Transplantable cell lines generated with NUP98-Hox fusion genes undergo leukemic progression by Meis1 independent of its binding to DNA. Leukemia 19 (4): 636-43, 2005. View Abstract

Schessl C, Rawat VP, Cusan M, Deshpande A, Kohl TM, Rosten PM, Spiekermann K, Humphries RK, Schnittger S, Kern W, Hiddemann W, Quintanilla-Martinez L, Bohlander SK, Feuring-Buske M, & Buske C. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest 115 (8): 2159-68, 2005. View Abstract

Gurevich RM, Aplan PD, & Humphries RK. NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation. Blood 104 (4): 1127-36, 2004. View Abstract

Imren S, Fabry ME, Westerman KA, Pawliuk R, Tang P, Rosten PM, Nagel RL, Leboulch P, Eaves CJ, & Humphries RK. High-level beta-globin expression and preferred intragenic integration after lentiviral transduction of human cord blood stem cells. J Clin Invest 114 (7): 953-62, 2004. View Abstract

Milsom MD, Woolford LB, Margison GP, Humphries RK, & Fairbairn LJ. Enhanced in vivo selection of bone marrow cells by retroviral-mediated coexpression of mutant O6-methylguanine-DNA-methyltransferase and HOXB4. Mol Ther 10 (5): 862-73, 2004. View Abstract

Nicolini FE, Cashman JD, Hogge DE, Humphries RK, & Eaves CJ. NOD/SCID mice engineered to express human IL-3, GM-CSF and Steel factor constitutively mobilize engrafted human progenitors and compromise human stem cell regeneration. Leukemia 18 (2): 341-7, 2004. View Abstract

Oh IH, Fabry ME, Humphries RK, Pawliuk R, Leboulch P, Hoffman R, Nagel RL, & Eaves C. Expression of an anti-sickling beta-globin in human erythroblasts derived from retrovirally transduced primitive normal and sickle cell disease hematopoietic cells. Exp Hematol 32 (5): 461-9, 2004. View Abstract

Pineault N, Abramovich C, Ohta H, & Humphries RK. Differential and common leukemogenic potentials of multiple NUP98-Hox fusion proteins alone or with Meis1. Mol Cell Biol 24 (5): 1907-17, 2004. View Abstract

Rawat VP, Cusan M, Deshpande A, Hiddemann W, Quintanilla-Martinez L, Humphries RK, Bohlander SK, Feuring-Buske M, & Buske C. Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukemia. Proc Natl Acad Sci U S A 101 (3): 817-22, 2004. View Abstract

Sauvageau G, Iscove NN, & Humphries RK. In vitro and in vivo expansion of hematopoietic stem cells. Oncogene 23 (43): 7223-32, 2004. View Abstract

Baran CP, Tridandapani S, Helgason CD, Humphries RK, Krystal G, & Marsh CB. The inositol 5’-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity. J Biol Chem 278 (40): 38628-36, 2003. View Abstract

Bjornsson JM, Larsson N, Brun AC, Magnusson M, Andersson E, Lundstrom P, Larsson J, Repetowska E, Ehinger M, Humphries RK, & Karlsson S. Reduced proliferative capacity of hematopoietic stem cells deficient in Hoxb3 and Hoxb4. Mol Cell Biol 23 (11): 3872-83, 2003. View Abstract

Brun AC, Fan X, Bjornsson JM, Humphries RK, & Karlsson S. Enforced adenoviral vector-mediated expression of HOXB4 in human umbilical cord blood CD34+ cells promotes myeloid differentiation but not proliferation. Mol Ther 8 (4): 618-28, 2003. View Abstract

Crow AR, Song S, Freedman J, Helgason CD, Humphries RK, Siminovitch KA, & Lazarus AH. IVIg-mediated amelioration of murine ITP via FcgammaRIIB is independent of SHIP1, SHP-1, and Btk activity. Blood 102 (2): 558-60, 2003. View Abstract

 Feuring-Buske M, Gerhard B, Cashman J, Humphries RK, Eaves CJ, & Hogge DE. Improved engraftment of human acute myeloid leukemia progenitor cells in beta 2-microglobulin-deficient NOD/SCID mice and in NOD/SCID mice transgenic for human growth factors. Leukemia 17 (4): 760-3, 2003. View Abstract

Helgason CD, Antonchuk J, Bodner C, & Humphries RK. Homeostasis and regeneration of the hematopoietic stem cell pool are altered in SHIP-deficient mice. Blood 102 (10): 3541-7, 2003. View Abstract

Krosl J, Austin P, Beslu N, Kroon E, Humphries RK, & Sauvageau G. In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein. Nat Med 9 (11): 1428-32, 2003. View Abstract

Krosl J, Beslu N, Mayotte N, Humphries RK, & Sauvageau G. The competitive nature of HOXB4-transduced HSC is limited by PBX1: the generation of ultra-competitive stem cells retaining full differentiation potential. Immunity 18 (4): 561-71, 2003. View Abstract

Larrivee B, Lane DR, Pollet I, Olive PL, Humphries RK, & Karsan A. Vascular endothelial growth factor receptor-2 induces survival of hematopoietic progenitor cells. J Biol Chem 278 (24): 22006-13, 2003. View Abstract

Pineault N, Buske C, Feuring-Buske M, Abramovich C, Rosten P, Hogge DE, Aplan PD, & Humphries RK. Induction of acute myeloid leukemia in mice by the human leukemia-specific fusion gene NUP98-HOXD13 in concert with Meis1. Blood 101 (11): 4529-38, 2003. View Abstract

Abramovich C, Chavez EA, Lansdorp PM, & Humphries RK. Functional characterization of multiple domains involved in the subcellular localization of the hematopoietic Pbx interacting protein (HPIP). Oncogene 21 (44): 6766-71, 2002. View Abstract

Antonchuk J, Sauvageau G, & Humphries RK. HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 109 (1): 39-45, 2002. View Abstract

Buske C, Feuring-Buske M, Abramovich C, Spiekermann K, Eaves CJ, Coulombel L, Sauvageau G, Hogge DE, & Humphries RK. Deregulated expression of HOXB4 enhances the primitive growth activity of human hematopoietic cells. Blood 100 (3): 862-8, 2002. View Abstract

Imren S, Payen E, Westerman KA, Pawliuk R, Fabry ME, Eaves CJ, Cavilla B, Wadsworth LD, Beuzard Y, Bouhassira EE, Russell R, London IM, Nagel RL, Leboulch P, & Humphries RK. Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells. Proc Natl Acad Sci U S A 99 (22): 14380-5, 2002. View Abstract

Miller CL, Imren S, Antonchuk J, Kalberer C, Fabry ME, Nagel RL, Humphries RK, & Eaves CJ. Feasibility of using autologous transplantation to evaluate hematopoietic stem cell-based gene therapy strategies in transgenic mouse models of human disease. Mol Ther 6 (3): 422-8, 2002. View Abstract

Nicolini FE, Imren S, Oh IH, Humphries RK, Leboulch P, Fabry ME, Nagel RL, & Eaves CJ. Expression of a human beta-globin transgene in erythroid cells derived from retrovirally transduced transplantable human fetal liver and cord blood cells. Blood 100 (4): 1257-64, 2002. View Abstract

Ohta H, Sawada A, Kim JY, Tokimasa S, Nishiguchi S, Humphries RK, Hara J, & Takihara Y. Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells. J Exp Med 195 (6): 759-70, 2002. View Abstract

Pineault N, Helgason CD, Lawrence HJ, & Humphries RK. Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny. Exp Hematol 30 (1): 49-57, 2002. View Abstract

Takeshita S, Namba N, Zhao JJ, Jiang Y, Genant HK, Silva MJ, Brodt MD, Helgason CD, Kalesnikoff J, Rauh MJ, Humphries RK, Krystal G, Teitelbaum SL, & Ross FP. SHIP-deficient mice are severely osteoporotic due to increased numbers of hyper-resorptive osteoclasts. Nat Med 8 (9): 943-9, 2002. View Abstract

Thorsteinsdottir U, Mamo A, Kroon E, Jerome L, Bijl J, Lawrence HJ, Humphries K, & Sauvageau G. Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood 99 (1): 121-9, 2002. View Abstract

Antonchuk J, Sauvageau G, & Humphries RK. HOXB4 overexpression mediates very rapid stem cell regeneration and competitive hematopoietic repopulation. Exp Hematol 29 (9): 1125-34, 2001. View Abstract

Bjornsson JM, Andersson E, Lundstrom P, Larsson N, Xu X, Repetowska E, Humphries RK, & Karlsson S. Proliferation of primitive myeloid progenitors can be reversibly induced by HOXA10. Blood 98 (12): 3301-8, 2001. View Abstract

Buske C, Feuring-Buske M, Antonchuk J, Rosten P, Hogge DE, Eaves CJ, & Humphries RK. Overexpression of HOXA10 perturbs human lymphomyelopoiesis in vitro and in vivo. Blood 97 (8): 2286-92, 2001. View Abstract

Latour S, Gish G, Helgason CD, Humphries RK, Pawson T, & Veillette A. Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product. Nat Immunol 2 (8): 681-90, 2001. View Abstract

Pawliuk R, Westerman KA, Fabry ME, Payen E, Tighe R, Bouhassira EE, Acharya SA, Ellis J, London IM, Eaves CJ, Humphries RK, Beuzard Y, Nagel RL, & Leboulch P. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science 294 (5550): 2368-71, 2001. View Abstract

Rufer N, Migliaccio M, Antonchuk J, Humphries RK, Roosnek E, & Lansdorp PM. Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential. Blood 98 (3): 597-603, 2001. View Abstract

Abramovich C, Shen WF, Pineault N, Imren S, Montpetit B, Largman C, & Humphries RK. Functional cloning and characterization of a novel nonhomeodomain protein that inhibits the binding of PBX1-HOX complexes to DNA. J Biol Chem 275 (34): 26172-7, 2000. View Abstract

Brauweiler A, Tamir I, Dal Porto J, Benschop RJ, Helgason CD, Humphries RK, Freed JH, & Cambier JC. Differential regulation of B cell development, activation, and death by the src homology 2 domain-containing 5’ inositol phosphatase (SHIP). J Exp Med 191 (9): 1545-54, 2000. View Abstract

Buske C, & Humphries RK. Homeobox genes in leukemogenesis. Int J Hematol 71 (4): 301-8, 2000. View Abstract

Helgason CD, Kalberer CP, Damen JE, Chappel SM, Pineault N, Krystal G, & Humphries RK. A dual role for Src homology 2 domain-containing inositol-5-phosphatase (SHIP) in immunity: aberrant development and enhanced function of b lymphocytes in ship -/- mice. J Exp Med 191 (5): 781-94, 2000. View Abstract

Hennemann B, Chuo JY, Schley PD, Lambie K, Humphries RK, & Eaves CJ. High-efficiency retroviral transduction of mammalian cells on positively charged surfaces. Hum Gene Ther 11 (1): 43-51, 2000. View Abstract

Hennemann B, Oh IH, Chuo JY, Kalberer CP, Schley PD, Rose-John S, Humphries RK, & Eaves CJ. Efficient retrovirus-mediated gene transfer to transplantable human bone marrow cells in the absence of fibronectin. Blood 96 (7): 2432-9, 2000. View Abstract

Kalberer CP, Pawliuk R, Imren S, Bachelot T, Takekoshi KJ, Fabry M, Eaves CJ, London IM, Humphries RK, & Leboulch P. Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human beta-globin in engrafted mice. Proc Natl Acad Sci U S A 97 (10): 5411-5, 2000. View Abstract

Lu L, Chappel MS, Humphries RK, & Osmond DG. Regulation of cell survival during B lymphopoiesis: increased pre-B cell apoptosis in CD24-transgenic mouse bone marrow. Eur J Immunol 30 (9): 2686-91, 2000. View Abstract

Metzler M, Helgason CD, Dragatsis I, Zhang T, Gan L, Pineault N, Zeitlin SO, Humphries RK, & Hayden MR. Huntingtin is required for normal hematopoiesis. Hum Mol Genet 9 (3): 387-94, 2000. View Abstract

Satterthwaite AB, Willis F, Kanchanastit P, Fruman D, Cantley LC, Helgason CD, Humphries RK, Lowell CA, Simon M, Leitges M, Tarakhovsky A, Tedder TF, Lesche R, Wu H, & Witte ON. A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton’s tyrosine kinase. Proc Natl Acad Sci U S A 97 (12): 6687-92, 2000. View Abstract

Ailles LE, Humphries RK, Thomas TE, & Hogge DE. Retroviral marking of acute myelogenous leukemia progenitors that initiate long-term culture and growth in immunodeficient mice. Exp Hematol 27 (11): 1609-20, 1999. View Abstract

Doheny JG, Jervis EJ, Guarna MM, Humphries RK, Warren RA, & Kilburn DG. Cellulose as an inert matrix for presenting cytokines to target cells: production and properties of a stem cell factor-cellulose-binding domain fusion protein. Biochem J 339 ( Pt 2): 429-34, 1999. View Abstract

Hennemann B, Conneally E, Pawliuk R, Leboulch P, Rose-John S, Reid D, Chuo JY, Humphries RK, & Eaves CJ. Optimization of retroviral-mediated gene transfer to human NOD/SCID mouse repopulating cord blood cells through a systematic analysis of protocol variables. Exp Hematol 27 (5): 817-25, 1999. View Abstract

Huber M, Helgason CD, Damen JE, Scheid M, Duronio V, Liu L, Ware MD, Humphries RK, & Krystal G. The role of SHIP in growth factor induced signalling. Prog Biophys Mol Biol 71 (3-4): 423-34, 1999. View Abstract

Huber M, Helgason CD, Damen JE, Scheid MP, Duronio V, Lam V, Humphries RK, & Krystal G. The role of the SRC homology 2-containing inositol 5’-phosphatase in Fc epsilon R1-induced signaling. Curr Top Microbiol Immunol 244: 29-41, 1999. View Abstract

Kawagoe H, Humphries RK, Blair A, Sutherland HJ, & Hogge DE. Expression of HOX genes, HOX cofactors, and MLL in phenotypically and functionally defined subpopulations of leukemic and normal human hematopoietic cells. Leukemia 13 (5): 687-98, 1999. View Abstract

Kim CH, Hangoc G, Cooper S, Helgason CD, Yew S, Humphries RK, Krystal G, & Broxmeyer HE. Altered responsiveness to chemokines due to targeted disruption of SHIP. J Clin Invest 104 (12): 1751-9, 1999. View Abstract

Krystal G, Damen JE, Helgason CD, Huber M, Hughes MR, Kalesnikoff J, Lam V, Rosten P, Ware MD, Yew S, & Humphries RK. SHIPs ahoy. Int J Biochem Cell Biol 31 (10): 1007-10, 1999. View Abstract

Metzler M, Chen N, Helgason CD, Graham RK, Nichol K, McCutcheon K, Nasir J, Humphries RK, Raymond LA, & Hayden MR. Life without huntingtin: normal differentiation into functional neurons. J Neurochem 72 (3): 1009-18, 1999. View Abstract

Thorsteinsdottir U, Sauvageau G, & Humphries RK. Enhanced in vivo regenerative potential of HOXB4-transduced hematopoietic stem cells with regulation of their pool size. Blood 94 (8): 2605-12, 1999. View Abstract

Conneally E, Eaves CJ, & Humphries RK. Efficient retroviral-mediated gene transfer to human cord blood stem cells with in vivo repopulating potential. Blood 91 (9): 3487-93, 1998. View Abstract

Helgason CD, Damen JE, Rosten P, Grewal R, Sorensen P, Chappel SM, Borowski A, Jirik F, Krystal G, & Humphries RK. Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span. Genes Dev 12 (11): 1610-20, 1998. View Abstract

Huber M, Helgason CD, Damen JE, Liu L, Humphries RK, & Krystal G. The src homology 2-containing inositol phosphatase (SHIP) is the gatekeeper of mast cell degranulation. Proc Natl Acad Sci U S A 95 (19): 11330-5, 1998. View Abstract

Huber M, Helgason CD, Scheid MP, Duronio V, Humphries RK, & Krystal G. Targeted disruption of SHIP leads to Steel factor-induced degranulation of mast cells. Embo J 17 (24): 7311-9, 1998. View Abstract

Pawliuk R, Bachelot T, Raftopoulos H, Kalberer C, Humphries RK, Bank A, & Leboulch P. Retroviral vectors aimed at the gene therapy of human beta-globin gene disorders. Ann N Y Acad Sci 850: 151-62, 1998. View Abstract

Bardy P, Conneally E, Emerman JT, Lansdorp PM, Goss G, Humphries RK, & Eaves CJ. Isolation and analysis of different subpopulations of normal human breast epithelial cells after their infection with a retroviral vector encoding a cell surface marker. Breast Cancer Res Treat 44 (2): 153-65, 1997. View Abstract

Damen JE, Liu L, Wakao H, Miyajima A, Rosten P, Jefferson AB, Majerus PW, Krosl J, Humphries RK, & Krystal G. The role of erythropoietin receptor tyrosine phosphorylation in erythropoietin-induced proliferation. Leukemia 11 Suppl 3: 423-5, 1997. View Abstract

Lawrence HJ, Helgason CD, Sauvageau G, Fong S, Izon DJ, Humphries RK, & Largman C. Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis. Blood 89 (6): 1922-30, 1997. View Abstract

Pawliuk R, Eaves CJ, & Humphries RK. Sustained high-level reconstitution of the hematopoietic system by preselected hematopoietic cells expressing a transduced cell-surface antigen. Hum Gene Ther 8 (13): 1595-604, 1997. View Abstract

Sauvageau G, Thorsteinsdottir U, Hough MR, Hugo P, Lawrence HJ, Largman C, & Humphries RK. Overexpression of HOXB3 in hematopoietic cells causes defective lymphoid development and progressive myeloproliferation. Immunity 6 (1): 13-22, 1997. View Abstract

Thorsteinsdottir U, Sauvageau G, Hough MR, Dragowska W, Lansdorp PM, Lawrence HJ, Largman C, & Humphries RK. Overexpression of HOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia. Mol Cell Biol 17 (1): 495-505, 1997. View Abstract

Thorsteinsdottir U, Sauvageau G, & Humphries RK. Hox homeobox genes as regulators of normal and leukemic hematopoiesis. Hematol Oncol Clin North Am 11 (6): 1221-37, 1997. View Abstract

Chappel MS, Hough MR, Mittel A, Takei F, Kay R, & Humphries RK. Cross-linking the murine heat-stable antigen induces apoptosis in B cell precursors and suppresses the anti-CD40-induced proliferation of mature resting B lymphocytes. J Exp Med 184 (5): 1638-49, 1996. View Abstract

Conneally E, Bardy P, Eaves CJ, Thomas T, Chappel S, Shpall EJ, & Humphries RK. Rapid and efficient selection of human hematopoietic cells expressing murine heat-stable antigen as an indicator of retroviral-mediated gene transfer. Blood 87 (2): 456-64, 1996. View Abstract

Damen JE, Liu L, Rosten P, Humphries RK, Jefferson AB, Majerus PW, & Krystal G. The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase. Proc Natl Acad Sci U S A 93 (4): 1689-93, 1996. View Abstract

Helgason CD, Sauvageau G, Lawrence HJ, Largman C, & Humphries RK. Overexpression of HOXB4 enhances the hematopoietic potential of embryonic stem cells differentiated in vitro. Blood 87 (7): 2740-9, 1996. View Abstract

Hough MR, Chappel MS, Sauvageau G, Takei F, Kay R, & Humphries RK. Reduction of early B lymphocyte precursors in transgenic mice overexpressing the murine heat-stable antigen. J Immunol 156 (2): 479-88, 1996. View Abstract

Krosl J, Damen JE, Krystal G, & Humphries RK. Interleukin-3 (IL-3) inhibits erythropoietin-induced differentiation in Ba/F3 cells via the IL-3 receptor alpha subunit. J Biol Chem 271 (44): 27432-7, 1996. View Abstract

Lawrence HJ, Sauvageau G, Humphries RK, & Largman C. The role of HOX homeobox genes in normal and leukemic hematopoiesis. Stem Cells 14 (3): 281-91, 1996. View Abstract

Medin JA, Migita M, Pawliuk R, Jacobson S, Amiri M, Kluepfel-Stahl S, Brady RO, Humphries RK, & Karlsson S. A bicistronic therapeutic retroviral vector enables sorting of transduced CD34+ cells and corrects the enzyme deficiency in cells from Gaucher patients. Blood 87 (5): 1754-62, 1996. View Abstract

Pawliuk R, Eaves C, & Humphries RK. Evidence of both ontogeny and transplant dose-regulated expansion of hematopoietic stem cells in vivo. Blood 88 (8): 2852-8, 1996. View Abstract

Shen WF, Chang CP, Rozenfeld S, Sauvageau G, Humphries RK, Lu M, Lawrence HJ, Cleary ML, & Largman C. Hox homeodomain proteins exhibit selective complex stabilities with Pbx and DNA. Nucleic Acids Res 24 (5): 898-906, 1996. View Abstract

Ware MD, Rosten P, Damen JE, Liu L, Humphries RK, & Krystal G. Cloning and characterization of human SHIP, the 145-kD inositol 5-phosphatase that associates with SHC after cytokine stimulation. Blood 88 (8): 2833-40, 1996. View Abstract

Damen JE, Wakao H, Miyajima A, Krosl J, Humphries RK, Cutler RL, & Krystal G. Tyrosine 343 in the erythropoietin receptor positively regulates erythropoietin-induced cell proliferation and Stat5 activation. Embo J 14 (22): 5557-68, 1995. View Abstract

Krosl J, Damen JE, Krystal G, & Humphries RK. Erythropoietin and interleukin-3 induce distinct events in erythropoietin receptor-expressing BA/F3 cells. Blood 85 (1): 50-6, 1995. View Abstract

Krystal G, Humphries K, & Damen J. A second erythropoietin receptor subunit. Blood 85 (9): 2641, 1995. View Abstract

Lawrence HJ, Sauvageau G, Ahmadi N, Lopez AR, LeBeau MM, Link M, Humphries K, & Largman C. Stage- and lineage-specific expression of the HOXA10 homeobox gene in normal and leukemic hematopoietic cells. Exp Hematol 23 (11): 1160-6, 1995. View Abstract

Lewis ME, Forsythe IJ, Marth JD, Brunzell JD, Hayden MR, & Humphries RK. Retroviral-mediated gene transfer and expression of human lipoprotein lipase in somatic cells. Hum Gene Ther 6 (7): 853-63, 1995. View Abstract

Migita M, Medin JA, Pawliuk R, Jacobson S, Nagle JW, Anderson S, Amiri M, Humphries RK, & Karlsson S. Selection of transduced CD34+ progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors. Proc Natl Acad Sci U S A 92 (26): 12075-9, 1995. View Abstract

Sauvageau G, Thorsteinsdottir U, Eaves CJ, Lawrence HJ, Largman C, Lansdorp PM, & Humphries RK. Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev 9 (14): 1753-65, 1995. View Abstract

Barnett MJ, Eaves CJ, Phillips GL, Gascoyne RD, Hogge DE, Horsman DE, Humphries RK, Klingemann HG, Lansdorp PM, Nantel SH, & et al. Autografting with cultured marrow in chronic myeloid leukemia: results of a pilot study. Blood 84 (3): 724-32, 1994. View Abstract

Hogge DE, Sutherland HJ, Cashman JD, Lansdorp PM, Humphries RK, & Eaves CJ. Cytokines acting early in human haematopoiesis. Baillieres Clin Haematol 7 (1): 49-63, 1994. View Abstract

Hough MR, Rosten PM, Sexton TL, Kay R, & Humphries RK. Mapping of CD24 and homologous sequences to multiple chromosomal loci. Genomics 22 (1): 154-61, 1994. View Abstract

Hough MR, Takei F, Humphries RK, & Kay R. Defective development of thymocytes overexpressing the costimulatory molecule, heat-stable antigen. J Exp Med 179 (1): 177-84, 1994. View Abstract

Leboulch P, Huang GM, Humphries RK, Oh YH, Eaves CJ, Tuan DY, & London IM. Mutagenesis of retroviral vectors transducing human beta-globin gene and beta-globin locus control region derivatives results in stable transmission of an active transcriptional structure. Embo J 13 (13): 3065-76, 1994. View Abstract

Pawliuk R, Kay R, Lansdorp P, & Humphries RK. Selection of retrovirally transduced hematopoietic cells using CD24 as a marker of gene transfer. Blood 84 (9): 2868-77, 1994. View Abstract

Rebel VI, Dragowska W, Eaves CJ, Humphries RK, & Lansdorp PM. Amplification of Sca-1+ Lin- WGA+ cells in serum-free cultures containing steel factor, interleukin-6, and erythropoietin with maintenance of cells with long-term in vivo reconstituting potential. Blood 83 (1): 128-36, 1994. View Abstract

Sauvageau G, Lansdorp PM, Eaves CJ, Hogge DE, Dragowska WH, Reid DS, Largman C, Lawrence HJ, & Humphries RK. Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc Natl Acad Sci U S A 91 (25): 12223-7, 1994. View Abstract

Fraser CC, Thacker JD, Hogge DE, Fatur-Saunders D, Takei F, & Humphries RK. Alterations in lymphopoiesis after hematopoietic reconstitution with IL-7 virus-infected bone marrow. J Immunol 151 (5): 2409-18, 1993. View Abstract

Damen J, Mui AL, Hughes P, Humphries K, & Krystal G. Erythropoietin-induced tyrosine phosphorylations in a high erythropoietin receptor-expressing lymphoid cell line. Blood 80 (8): 1923-32, 1992. View Abstract

Eaves CJ, Sutherland HJ, Udomsakdi C, Lansdorp PM, Szilvassy SJ, Fraser CC, Humphries RK, Barnett MJ, Phillips GL, & Eaves AC. The human hematopoietic stem cell in vitro and in vivo. Blood Cells 18 (2): 301-7, 1992. View Abstract

Fraser CC, Szilvassy SJ, Eaves CJ, & Humphries RK. Proliferation of totipotent hematopoietic stem cells in vitro with retention of long-term competitive in vivo reconstituting ability. Proc Natl Acad Sci U S A 89 (5): 1968-72, 1992. View Abstract

Hughes PF, Thacker JD, Hogge D, Sutherland HJ, Thomas TE, Lansdorp PM, Eaves CJ, & Humphries RK. Retroviral gene transfer to primitive normal and leukemic hematopoietic cells using clinically applicable procedures. J Clin Invest 89 (6): 1817-24, 1992. View Abstract

Mui AL, Kay RJ, Humphries RK, & Krystal G. Ligand-induced phosphorylation of the murine interleukin 3 receptor signals its cleavage. Proc Natl Acad Sci U S A 89 (22): 10812-6, 1992. View Abstract

Mui AL, Kay RJ, Humphries RK, & Krystal G. Purification of the murine interleukin 3 receptor. J Biol Chem 267 (23): 16523-30, 1992. View Abstract

Munt B, Erb S, Humphries K, Shepherd J, Scudamore C, Anderson F, Lam V, Shackleton C, & Krystal G. Monitoring hemangioblastoma tumor burden using plasma erythropoietin levels. Int J Hematol 56 (2): 185-7, 1992. View Abstract

Turhan AG, Cashman JD, Eaves CJ, Humphries RK, & Eaves AC. Variable expression of features of normal and neoplastic stem cells in patients with thrombocytosis. Br J Haematol 82 (1): 50-7, 1992. View Abstract

Barnett MJ, Sutherland HJ, Eaves AC, Hogge DE, Humphries RK, Klingemann HG, Lansdorp PM, Phillips GL, Reece DE, Shepherd JD, & et al. Human hematopoietic stem cells in long-term culture: quantitation and manipulation. Bone Marrow Transplant 7 Suppl 1: 70, 1991. View Abstract

Dougherty GJ, Landorp PM, Cooper DL, & Humphries RK. Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte “homing” receptor expressed by hemopoietic cells. J Exp Med 174 (1): 1-5, 1991. View Abstract

Eaves CJ, Cashman JD, Kay RJ, Dougherty GJ, Otsuka T, Gaboury LA, Hogge DE, Lansdorp PM, Eaves AC, & Humphries RK. Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. II. Analysis of positive and negative regulators produced by stromal cells within the adherent layer. Blood 78 (1): 110-7, 1991. View Abstract

Eaves CJ, Cashman JD, Sutherland HJ, Otsuka T, Humphries RK, Hogge DE, Lansdorp PL, & Eaves AC. Molecular analysis of primitive hematopoietic cell proliferation control mechanisms. Ann N Y Acad Sci 628: 298-306, 1991. View Abstract

Eaves CJ, Sutherland HJ, Cashman JD, Otsuka T, Lansdorp PM, Humphries RK, Eaves AC, & Hogge DE. Regulation of primitive human hematopoietic cells in long-term marrow culture. Semin Hematol 28 (2): 126-31, 1991. View Abstract

Hogge DE, Cashman JD, Humphries RK, & Eaves CJ. Differential and synergistic effects of human granulocyte-macrophage colony-stimulating factor and human granulocyte colony-stimulating factor on hematopoiesis in human long-term marrow cultures. Blood 77 (3): 493-9, 1991. View Abstract

Kay R, Rosten PM, & Humphries RK. CD24, a signal transducer modulating B cell activation responses, is a very short peptide with a glycosyl phosphatidylinositol membrane anchor. J Immunol 147 (4): 1412-6, 1991. View Abstract

Otsuka T, Eaves CJ, Humphries RK, Hogge DE, & Eaves AC. Lack of evidence for abnormal autocrine or paracrine mechanisms underlying the uncontrolled proliferation of primitive chronic myeloid leukemia progenitor cells. Leukemia 5 (10): 861-8, 1991. View Abstract

Otsuka T, Humphries RK, Hogge DE, Eaves AC, & Eaves CJ. Continuous activation of primitive hematopoietic cells in long-term human marrow cultures containing irradiated tumor cells. J Cell Physiol 148 (3): 370-9, 1991. View Abstract

St Amand J, Beard C, Humphries K, & Astell CR. Analysis of splice junctions and in vitro and in vivo translation potential of the small, abundant B19 parvovirus RNAs. Virology 183 (1): 133-42, 1991. View Abstract

Turhan AG, Eaves CJ, Humphries RK, Phillips GL, & Eaves AC. Reversing clonality in leukemia. Semin Hematol 28 (3 Suppl 4): 5-8, 1991. View Abstract

Fraser CC, Eaves CJ, Szilvassy SJ, & Humphries RK. Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells. Blood 76 (6): 1071-6, 1990. View Abstract

Iyer J, Duerst RE, Looney JN, Humphries RK, Abboud CN, & Frantz CN. An 80,000-kd glycoprotein cell surface antigen found only on nonhematopoietic cells in human bone marrow. Exp Hematol 18 (5): 384-9, 1990. View Abstract

Kay R, Dougherty GJ, & Humphries RK. Heterogeneous modifications of the 114/A10 protein of interleukin-3-dependent cells are concentrated in a highly repetitive amino-terminal domain. J Biol Chem 265 (9): 4962-8, 1990. View Abstract

Kay R, Takei F, & Humphries RK. Expression cloning of a cDNA encoding M1/69-J11d heat-stable antigens. J Immunol 145 (6): 1952-9, 1990. View Abstract

Szilvassy SJ, Humphries RK, Lansdorp PM, Eaves AC, & Eaves CJ. Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy. Proc Natl Acad Sci U S A 87 (22): 8736-40, 1990. View Abstract

Turhan AG, Humphries RK, Eaves CJ, Barnett MJ, Phillips GL, Kalousek DK, Klingemann HG, Lansdorp PL, Reece DE, Shepherd JD, & et al. Detection of breakpoint cluster region- negative and nonclonal hematopoiesis in vitro and in vivo after transplantation of cells selected in cultures of chronic myeloid leukemia marrow. Blood 76 (11): 2404-10, 1990. View Abstract

Wognum AW, Lansdorp PM, Humphries RK, & Krystal G. Detection and isolation of the erythropoietin receptor using biotinylated erythropoietin. Blood 76 (4): 697-705, 1990. View Abstract

Dougherty GJ, Dougherty ST, Kay RJ, Landsdorp P, & Humphries RK. Identification and characterization of 114/A10, an antigen highly expressed on the surface of murine myeloid and erythroid progenitor cells and IL-3-dependent cell lines. Exp Hematol 17 (8): 877-82, 1989. View Abstract

Dougherty GJ, Kay RJ, & Humphries RK. Molecular cloning of 114/A10, a cell surface antigen containing highly conserved repeated elements, which is expressed by murine hemopoietic progenitor cells and interleukin-3-dependent cell lines. J Biol Chem 264 (11): 6509-14, 1989. View Abstract

Hughes PF, Eaves CJ, Hogge DE, & Humphries RK. High-efficiency gene transfer to human hematopoietic cells maintained in long-term marrow culture. Blood 74 (6): 1915-22, 1989. View Abstract

Szilvassy SJ, Fraser CC, Eaves CJ, Lansdorp PM, Eaves AC, & Humphries RK. Retrovirus-mediated gene transfer to purified hemopoietic stem cells with long-term lympho-myelopoietic repopulating ability. Proc Natl Acad Sci U S A 86 (22): 8798-802, 1989. View Abstract

Szilvassy SJ, Lansdorp PM, Humphries RK, Eaves AC, & Eaves CJ. Isolation in a single step of a highly enriched murine hematopoietic stem cell population with competitive long-term repopulating ability. Blood 74 (3): 930-9, 1989. View Abstract

Turhan AG, Humphries RK, Phillips GL, Eaves AC, & Eaves CJ. Clonal hematopoiesis demonstrated by X-linked DNA polymorphisms after allogeneic bone marrow transplantation. N Engl J Med 320 (25): 1655-61, 1989. View Abstract

Fraser C, Humphries RK, & Mager DL. Chromosomal distribution of the RTVL-H family of human endogenous retrovirus-like sequences. Genomics 2 (4): 280-7, 1988. View Abstract

Humphries RK, Abraham S, Krystal G, Lansdorp P, Lemoine F, & Eaves CJ. Activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells. Exp Hematol 16 (9): 774-81, 1988. View Abstract

Lemoine FM, Humphries RK, Abraham SD, Krystal G, & Eaves CJ. Partial characterization of a novel stromal cell-derived pre-B-cell growth factor active on normal and immortalized pre-B cells. Exp Hematol 16 (8): 718-26, 1988. View Abstract

Lemoine FM, Krystal G, Humphries RK, & Eaves CJ. Autocrine production of pre-B-cell stimulating activity by a variety of transformed murine pre-B-cell lines. Cancer Res 48 (22): 6438-43, 1988. View Abstract

Turhan AG, Eaves CJ, Kalousek DK, Eaves AC, & Humphries RK. Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 71 (5): 1495-8, 1988. View Abstract

Turhan AG, Humphries RK, Cashman JD, Cuthbert DA, Eaves CJ, & Eaves AC. Transient suppression of clonal hemopoiesis associated with pregnancy in a patient with a myeloproliferative disorder. J Clin Invest 81 (6): 1999-2003, 1988. View Abstract

Hogge DE, & Humphries RK. Gene transfer to primary normal and malignant human hemopoietic progenitors using recombinant retroviruses. Blood 69 (2): 611-7, 1987. View Abstract

Wong PM, Humphries RK, Chen TR, & Eaves CJ. Evidence for a multistep pathogenesis in the generation of tumorigenic cell lines from hemopoietic colonies exposed to Abelson virus in vitro. Exp Hematol 15 (3): 280-7, 1987. View Abstract

Dover GJ, Humphries RK, Moore JG, Ley TJ, Young NS, Charache S, & Nienhuis AW. Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production. Blood 67 (3): 735-8, 1986. View Abstract

Moore JG, Humphries RK, Frank MM, & Young N. Characterization of the hematopoietic defect in paroxysmal nocturnal hemoglobinuria. Exp Hematol 14 (3): 222-9, 1986. View Abstract

Anderson WF, Goldberg S, Kantoff P, Berg P, Eglitis M, & Humphries RK. Attempts at gene therapy in beta-thalassemic mice. Ann N Y Acad Sci 445: 445-51, 1985. View Abstract

Dover GJ, Humphries RK, Young N, Ley T, Boyer S, Charache S, & Nienhuis A. Pharmacologic manipulation of fetal hemoglobin synthesis. Prog Clin Biol Res 191: 447-54, 1985. View Abstract

Greenberger JS, Humphries RK, Messner H, Reid DM, & Sakakeeny MA. Molecularly cloned and expressed murine T-cell gene product is biologically similar to interleukin-3. Exp Hematol 13 (4): 249-60, 1985. View Abstract

Humphries RK, Berg P, DiPietro J, Bernstein S, Baur A, Nienhuis AW, & Anderson WF. Transfer of human and murine globin-gene sequences into transgenic mice. Am J Hum Genet 37 (2): 295-310, 1985. View Abstract

Humphries RK, Dover G, Young NS, Moore JG, Charache S, Ley T, & Nienhuis AW. 5-Azacytidine acts directly on both erythroid precursors and progenitors to increase production of fetal hemoglobin. J Clin Invest 75 (2): 547-57, 1985. View Abstract

Karlsson S, Humphries RK, Gluzman Y, & Nienhuis AW. Transfer of genes into hematopoietic cells using recombinant DNA viruses. Proc Natl Acad Sci U S A 82 (1): 158-62, 1985. View Abstract

Nienhuis AW, Ley TJ, Humphries RK, Young NS, & Dover G. Pharmacological manipulation of fetal hemoglobin synthesis in patients with severe beta-thalassemia. Ann N Y Acad Sci 445: 198-211, 1985. View Abstract

Chen MJ, Shimada T, Moulton AD, Cline A, Humphries RK, Maizel J, & Nienhuis AW. The functional human dihydrofolate reductase gene. J Biol Chem 259 (6): 3933-43, 1984. View Abstract

Humphries RK, Ley TJ, Anagnou NP, Baur AW, & Nienhuis AW. Beta O-39 thalassemia gene: a premature termination codon causes beta-mRNA deficiency without affecting cytoplasmic beta-mRNA stability. Blood 64 (1): 23-32, 1984. View Abstract

Humphries RK, & Young N. Aplastic anemia and stem cell biology. Prog Clin Biol Res 148: 3-12, 1984. View Abstract

Young N, Harrison M, Moore J, Mortimer P, & Humphries RK. Direct demonstration of the human parvovirus in erythroid progenitor cells infected in vitro. J Clin Invest 74 (6): 2024-32, 1984. View Abstract

Young NS, Moore JG, & Humphries RK. The human parvovirus and in vitro hematopoietic colony formation. Prog Clin Biol Res 148: 129-39, 1984. View Abstract

Young NS, Mortimer PP, Moore JG, & Humphries RK. Characterization of a virus that causes transient aplastic crisis. J Clin Invest 73 (1): 224-30, 1984. View Abstract

Zoumbos NC, Ferris WO, Hsu SM, Goodman S, Griffith P, Sharrow SO, Humphries RK, Nienhuis AW, & Young N. Analysis of lymphocyte subsets in patients with aplastic anaemia. Br J Haematol 58 (1): 95-105, 1984. View Abstract

Cashman J, Henkelman D, Humphries K, Eaves C, & Eaves A. Individual BFU-E in polycythemia vera produce both erythropoietin dependent and independent progeny. Blood 61 (5): 876-84, 1983. View Abstract

Dean A, Ley TJ, Humphries RK, Fordis CM, Jr., & Schechter AN. Abundance and structure of globin mRNA in K562 human leukemia cells. Prog Clin Biol Res 134: 323-34, 1983. View Abstract

Dean A, Ley TJ, Humphries RK, Fordis M, & Schechter AN. Inducible transcription of five globin genes in K562 human leukemia cells. Proc Natl Acad Sci U S A 80 (18): 5515-9, 1983. View Abstract

Goldsmith ME, Humphries RK, Ley T, Cline A, Kantor JA, & Nienhuis AW. “Silent” nucleotide substitution in a beta+-thalassemia globin gene activates splice site in coding sequence RNA. Proc Natl Acad Sci U S A 80 (8): 2318-22, 1983. View Abstract

Greenberger JS, Sakakeeny MA, Humphries RK, Eaves CJ, & Eckner RJ. Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci U S A 80 (10): 2931-5, 1983. View Abstract

Humphries RK, Ley T, Goldsmith ME, Kantor JA, Cline AC, & Nienhuis AW. “Silent” nucleotide substitution in codon 24 of a beta+ thalassemia globin gene activates splice site in coding sequence RNA. Prog Clin Biol Res 134: 123-6, 1983. View Abstract

Mortimer PP, Humphries RK, Moore JG, Purcell RH, & Young NS. A human parvovirus-like virus inhibits haematopoietic colony formation in vitro. Nature 302 (5907): 426-9, 1983. View Abstract

Humphries RK, Ley T, Turner P, Moulton AD, & Nienhuis AW. Differences in human alpha-, beta- and delta-globin gene expression in monkey kidney cells. Cell 30 (1): 173-83, 1982. View Abstract

Ley TJ, DeSimone J, Anagnou NP, Keller GH, Humphries RK, Turner PH, Young NS, Keller P, & Nienhuis AW. 5-azacytidine selectively increases gamma-globin synthesis in a patient with beta+ thalassemia. N Engl J Med 307 (24): 1469-75, 1982. View Abstract

Humphries RK, Eaves AC, & Eaves CJ. Self-renewal of hemopoietic stem cells during mixed colony formation in vitro. Proc Natl Acad Sci U S A 78 (6): 3629-33, 1981. View Abstract

Eaves CJ, Humphries RK, & Eaves AC. Marrow flask cultures—a system for examining early erythropoietic differentiation events. Blood Cells 5 (3): 377-87, 1979. View Abstract

Humphries RK, Eaves AC, & Eaves CJ. Characterization of a primitive erythropoietic progenitor found in mouse marrow before and after several weeks in culture. Blood 53 (4): 746-63, 1979. View Abstract

Humphries RK, Jacky PB, Dill FJ, Eaves AC, & Eaves CJ. CFU-S in individual erythroid colonies derived in vitro from adult mouse marrow. Nature 279 (5715): 718-20, 1979. View Abstract

Humphries RK, & Miller RG. Volume analysis of human peripheral blood leukocytes. Ser Haematol 5 (2): 142-62, 1972. View Abstract

 

Lab Members


Humphries Lab

Postdoctoral Fellows
Dr. Eric Yung, PhD
Dr. Ping Xiang, PhD
Dr. Tobias Berg, MD
Dr. Jens Ruschmann, PhD

Graduate Students
Michelle Miller
Sanja Sekulovic
Courteney Lai
Paul Miller



Research/Co-op Students
Anisa Salmi
Dennis Lo
Garrett Rhyasen
Sandy Wong
Harry Chang
Tracee Wee

Research Associate
Dr. Suzan Imren, MD

Technicians
Patty Rosten

Open Positions

None available at this time.

Mailing Address:

   

Terry Fox Laboratory
BC Cancer Agency
675 West 10th Avenue,
Vancouver BC
Canada V5Z 1L3

Email:
khumphri@bccrc.ca
Phone Number:
604-675-8140

Terry Fox Laboratory
BC Cancer Agency
675 West 10th Avenue,
Vancouver BC
Canada V5Z 1L3

 

© 2007. BC Cancer Agency. All rights reserved.
www.terryfoxlab.ca  =  tfl.bccrc.ca