Position:
Professor
Division:
Hematology
Research Interests:

Gene Transfer and Gene Therapy, Hematology/Stem Cell Biology, Molecular Genetic Regulaton of Hemopoiesis

Education:
B.Sc. (Honors), University of Alberta, Physics
M.Sc., University of Toronto, Biophysics
MD, University of British Columbia
Ph.D., University of British Columbia, Medical Genetics
Recent Publications:
  • •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: 109-118, 2006.
  • •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 34:1191-1036, 2006.
  • •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: 1030-1036, 2006.
  • •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: e173-0687-0698, 2006.
  • •Deshpande AJ, Cusan M, Rawat VPS, Krause A, Reuter H, Quintanilla-Martinez L, Pott C, Kuchenbauer F, Ahmed F, Lichter P, Kneba M, Hiddemann W, Humphries RK, Bohlander SK, Feuring-Buske M & Buske C. Acute myeloid leukemia is propagated by a transformed lymphoid progenitor in a mouse model of CALM/AF10 positive leukemia.  Cancer Cell 10: 363-374, 2006.
  • •Cellot S, Krosl J, Chagraoui J, Humphries RK & Sauvageau G. Sustained in vitro trigger of self-renewal divisions in Hoxb4hiPbx1lo hematopoietic stem cells (submitted).
  • •Hirose K, Abramovich C & 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 (submitted).
  • •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: 1293-1302, 2007.
  • •Ohta H*, Sekulovic S*, Bakovic S, Eaves CJ, Pineault N, Gasparetto M, Smith C, Sauvageau G & Humphries RK. Near-maximal expansion of hematopoietic stem cells in culture using NUP98-HOX fusions.  Exp Hematol 35: 817-830, 2007. (*Authors contributed equally to this study).
  • •Ohta H, Sekulovic S, Bakovic S, Eaves CJ, Pineault N, Sauvageau G & Humphries K. Near maximal expansions of hematopoietic stem cells in culture using NUP98-HOX fusion genes (submitted).
  • •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: e768 2007.
  • •Zhang XB, Schwartz JS, Humphries RK & Kiem HP. Effects of HOXB4 overexpression on ex vivo expansion and immortalization of hematopoietc cells from different species.  Stem Cells 25: 2074-2081, 2007.
  • •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: 845-859, 2008.
  • •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  73: 555-564, 2008.
  • •Hirose K, Abramovich C & 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  27:  6056-67, 2008.
  • •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).
  • •Zhang XB, Beard BC, Trobridge GD, Wood BL, Sale GE, Sud R, Humphries RK & Kiem H-P. High incidence of leukemia after stem-cell gene therapy in large animals with a HOXB4-expressing vector.  J Clin Invest 118: 1502-1510, 2008.
  • •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, 2009.
  • •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 113: 1432-1443, 2009. (*authors contributed equally to this study; **co-senior authors).
  • •Heuser M, Kuchenbauer F, Argiropoulos B, Sekulovic S, Leung M, Stasiak M, Ganser A & Humphries RK. Priming reloaded?  Blood 114: 925-926, 2009.
  • •Heuser M, Sly L, 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 114: 3983-3993, 2009.
  • •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.
  • •Argiropoulos B, Palmqvist L, Imren S, Miller M, Rouhi A, Mager DL & Humphries RK. Meis1 disrupts the genomic imprint of Dlk1 in a NUP98-HOXD13 leukemia model. Leukemia 24: 1788-1791, 2010.
  • •Argiropoulos B, Yung E, Xiang P, Lo CY, Kuchenbauer F, Palmqvist L, Reindl C, Heuser M, Sekulovic S, Rosten P, Muranyi A, Goh S-L, 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.
  • •Eaves CJ & Humphries RK. Acute myeloid leukemia and the Wnt pathway. N Engl J Med 362: 2326-2327, 2010.
  • •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.
  • •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.
  • •Heuser M & Humphries RK. Biologic and experimental variation of measured cancer stem cells. Cell Cycle 9: 909-12, 2010.
  • •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: 174-179, 2010.
  • •Imren S*, Zhang XB*, Humphries RK* & Kiem HP*. Insights into leukemia-initiating cell frequency and self-renewal from a novel canine model of leukemia. Exp Hematol 39: 124-32, 2010.
  • •Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer 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. Insights into leukemia-initiating cell frequency and self-renewal from a novel canine model of leukemia Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet 42: 181-185, 2010.
  • •Petriv OI, Kuchenbauer F, Delaney AD, Lecault V, White A, Kent D, Marmolejo L, Heuser M, Berg T, Copley M, Ruschmann J, Sekulovic S, Benz C, Kuroda E, Ho V, Antignano F, Halim T, Giambra V, Krystal G, Takei F, Weng AP, Piret J, Eaves C, Marra MA, Humphries RK & Hansen CL. Comprehensive microRNA expression profiling of the hematopoietic hierarchy. Proc Natl Acad Sci USA 107: 15443-15448, 2010.
  • •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.
  • •Starczynowski DT, Kuchenbauer F, Wegrzyn J, Rouhi A, Petriv O, Hansen CL, Humphries RK & Karsan A. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol 39:167-178, 2010.
  • •Starczynowski DT, Morin R, McPherson A, Lam J, Chari R, Wegrzyn J, Kuchenbauer F, Hirst M, Tohyama K, Humphries RK, Lam WL, Marra M & Karsan A. Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations. Blood 117: 595-604, 2010.
  • •Watts KL, Delaney C, Humphries RK, Bernstein I & Kiem HP. Combination of HOXB4 and delta-1 ligand improves expansion of cord blood cells. Blood 116: 5859-66, 2010.
  • •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 38: 798-828, 2010.
  • •Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, Morin RD, Mungall AJ, Meissner B, Boyle M, Marquez VE, Marra MA, Gascoyne RD, Humphries RK, Arrowsmith CH, Morin GB & Aparicio SA. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood 2010. (Epub ahead of print).
  • •Yung E, Sekulovic S, Argiropoulos B, Lai CK, Leung M, Berg T, Vollett S, Chang VCD, Wan A, Wong S & Humphries RK. Delineating domains and functions of NUP98 contributing to the leukemogenic activity of NUP98-HOX fusions. Leuk Res 2010. (Epub ahead of print).
  • •Petriv OI, Hansen CL, Humphries RK & Kuchenbauer F. Probing the complexity of miRNA expression across hematopoiesis. Cell Cycle 10:2-3, 2011.