• Schultz, Kirk

    Titles
    Head, Childhood Cancer & Blood Research cluster, CFRI
    Senior Clinician Scientist, CFRI
    Professor, Division of Hematology and Oncology, Department of Pediatrics, University of British Columbia
    Degrees / Designations
    MD
    Primary Area of Research
    Childhood Cancer & Blood Research
    Secondary Area(s) of Research
    Immunity in Health & Disease
    Phone
    604-875-3886 / 604-875-2406
    Fax
    604-875-2911
    Lab Phone
    Mailing Address
    Child & Family Research Institute
    Room A5-165, 950 West 28th Avenue
    Vancouver, BC V5Z 4H4
    Affiliate Websites
    Research Areas
    • Immune system
    • Childhood leukemia
    • Blood and marrow transplantation
    • Tumour immunology 
    Summary

    We are attempting to harness the immune system to cure child leukemia and to use blood-derived stem cells to cure other life threatening childhood diseases.

    Currently, blood and marrow transplantation (BMT) is the only successful form of immune therapy for childhood leukemia. Our research group focuses on harnessing the immune forces unleashed by BMT to improve immune therapy for childhood leukemia. By increasing our understanding of these important immune forces, we hope to also improve the ability to provide safe tissue transplants when needed. Lastly, our group is focused on developing approaches to extend the ability to use blood-derived stem cells to regenerate damaged tissues, correct the immune system, and save children and adolescents from life threatening childhood diseases.

    Current Projects
    My work has evaluated clinically driven issues related to hematopoietic cell transplantation. Clinical investigations have focused on age-related factors affecting graph-versus-host disease (GVHD), graft-failure and graft-versus-leukemia (GVL). Laboratory investigations have used pre-clinical models and the performance of correlative studies in humans to investigate the mechanisms of GVHD and GVL and to develop experimental approaches to modulate these phenomena.

    Our laboratory has evaluated the hypothesis that manipulation of MHC class II antigen presentation can alter T cell responses to endogenous antigens. We have investigated the importance of two MHC class II antigen presenting cells in vivo, B cells and dendritic cells, for T cell priming responses to leukemia, and minor histocompatibility antigens (MiHC). We have also investigated whether inhibition of MHC class II antigen presentation by lysosomotropic agents such as chloroquine can inhibit T cell responses to MiHC and development of GVHD. We have translated these pre-clinical observations into clinical studies. We have been one of the first groups to identify chronic GVHD biomarkers in children.

    We are also investigating approaches to increasing T cell responses to leukemia by immunization approaches focused on overcoming defects in antigen presentation of endogenous antigens that are either specific to the malignancy or over-expressed in the malignancy. We have focused on the ability of all cells to act as antigen presenting cells and utilizing TLR agonists that affect both leukemic cell immunogenicity and anti-leukemia immune response.

    I have been very involved in developing clinical trials focused on improving therapy for GVHD and Acute Lymphoblastic Leukemia. I am a prominent member of clinical co-operative groups including the Children’s Oncology Group (COG), Canadian Blood and Marrow Transplantation Group (CBMTG), Chronic GHVD Consensus Group (NIH sponsored), and C17 (a Canadian pediatric oncology research group). I am currently the group chair of the Pediatric BMT Consortium, a cooperative group that includes over 85 pediatric BMT centers in North America, Australia and New Zealand.
    Selected Publications
    Suttorp M, Yaniv I, Schultz KR. Controversies in the treatment of CML in children and adolescents: TKIs versus BMT? Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S115-22.

    Goyal RK, Lin Y, Schultz KR, Ferrell RE, Kim Y, Fairfull L, Livote E, Yanik G, Atlas M. Tumor necrosis factor-alpha gene polymorphisms are associated with severity of acute graft-versus-host disease following matched unrelated donor bone marrow transplantation in children: a Pediatric Blood and Marrow Transplant Consortium study. Biol Blood Marrow Transplant. 2010 Jul;16(7):927-936.e1. Epub 2010 Jan 25.

    Pulsipher MA, Horwitz EM, Haight AE, Kadota R, Chen AR, Frangoul H, Cooper LJ, Jacobsohn DA, Goyal RK, Mitchell D, Nieder ML, Yanik G, Cowan MJ, Soni S, Gardner S, Shenoy S, Taylor D, Cairo M, Schultz KR. Advancement of pediatric blood and marrow transplantation research in North America: priorities of the Pediatric Blood and Marrow Transplant Consortium. Biol Blood Marrow Transplant. 2010 Sep;16(9):1212-21. Epub 2010 Jan 14. Review.

    Schultz KR, Prestidge T, Camitta B.Philadelphia chromosome-positive acute lymphoblastic leukemia in children: new and emerging treatment options. Expert Rev Hematol. 2010 Dec;3(6):731-42.

    Shaw PJ, Kan F, Woo Ahn K, Spellman SR, Aljurf M, Ayas M, Burke M, Cairo MS, Chen AR, Davies SM, Frangoul H, Gajewski J, Gale RP, Godder K, Hale GA, Heemskerk MB, Horan J, Kamani N, Kasow KA, Chan KW, Lee SJ, Leung WH, Lewis VA, Miklos D, Oudshoorn M, Petersdorf EW, Ringdén O, Sanders J, Schultz KR, Seber A, Setterholm M, Wall DA, Yu L, Pulsipher MA.Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors. Blood. 2010 Nov 11;116(19):4007-15. Epub 2010 Jul 29.

    Rolf N, Kariminia A, Ivison S, Schultz KR. Therapeutic Potential for Toll-Like-Receptor 2 Agonists in Pediatric Acute Lymphoblastic Leukemia (pre-B ALL): Induction of Apoptosis and Anti-ALL Immunogenicity. (ASH Travel Award) 52. Annual Meeting of the American Society of Hematology, Dec.3-7, 2010, Orlando/FL, USA, Blood 116, 21: 381 (2010).

    Rolf N, Kariminia A, Ivison S, Schultz KR. In Vitro Studies On The Impact Of TLR2 Agonists On The Cytotoxic Potential Of Chemotherapy And Immune Responses In pre-B Acute Lymphoblastic Leukemia (ALL). 2nd International Conference on Immunotherapy in Pediatric Oncology, Oct.11-12, 2010 Houston/TX, USA.

    Woodard P, Carpenter PA, Davies SM, Gross TG, He W, Zhang MJ, Horn BN, Margolis DA, Perentesis JP, Sanders JE, Schultz KR, Seber A, Woods WG, Eapen M. Unrelated donor bone marrow transplantation for myelodysplastic syndrome in children. Biol Blood Marrow Transplant. 2010 Aug 30.

    Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010 Aug 10;28(23):3730-8. Epub 2010 Jul 12.

    Schultz KR. Haploidentical transplantation in children. Blood. 2010 Apr 29;115(17):3420-1

    Baird K, Cooke K, Schultz KR. Chronic graft-versus-host disease (GVHD) in children. Pediatr Clin North Am. 2010 Feb;57(1):297-322. Review.

    Cuvelier GD, Kariminia A, Fujii H, Aslanian S, Wall D, Goldman F, Grupp SA, Dunn SE, Krailo M, Shapiro LH, Gilman A, Schultz KR. Anti-CD13 Abs in children with extensive chronic GVHD and their relation to soluble CD13 after allogeneic blood and marrow transplantation from a Children's Oncology Groups Study, ASCT0031. Bone Marrow Transplant. 2010 Nov;45(11):1653-7. Epub 2010 Mar 1.

    Lehman AM, Schultz KR, Poskitt K, Bjornson B, Keyes R, Waters PJ, Clarke LA, Everett R, McConnell D, Stockler S. Intracranial calcification after cord blood neonatal transplantation for krabbe disease. Neuropediatrics. 2009 Aug;40(4):189-91. Epub 2010 Feb 4.

    Medyouf H, Gao X, Armstrong F, Gusscott S, Liu Q, Gedman AL, Matherly LH, Schultz KR, Pflumio F, You MJ, Weng AP. Acute T-cell leukemias remain dependent on Notch signaling despite PTEN and INK4A/ARF loss. Blood. 2010 Feb 11;115(6):1175-84. Epub 2009 Dec 11.

    Reid, GDS, Grupp, S, Schultz KR.: Tumor Immunology and Immunotherapy In: Carroll W and Finlay J, eds. Cancer in Children and Adolescents Jones & Bartlett Publishers, Sudbury Mass; 2009. Chap 4.

    Schultz KR.: Pathophysiology Of Chronic GVHD In: Vogelsang G, Pavletic S, eds. Chronic Graft Versus Host Disease: Principles And Practice Of Interdisciplinary Management Cambridge Press; 2009.Chap 3,p17-45.

    Cuvelier GD, Schultz KR, Davis J, Hirschfeld AF, Junker AK, Tan R, Turvey SE.: Optimizing outcomes of hematopoietic stem cell transplantation for severe combined immunodeficiency. Clin Immunol. 2009 May;131(2):179-88.

    Griffith LM, Pavletic SZ, Lee SJ, Martin PJ, Schultz KR, Vogelsang GB.: Chronic Graft-versus-Host Disease--implementation of the National Institutes of Health Consensus Criteria for Clinical Trials. Biol Blood Marrow Transplant. 2008 Apr;14(4):379-84.

    Hunger SP, Loh KM, Baker KS, Schultz KR.: Controversies of and unique issues in hematopoietic cell transplantation for infant leukemia. Biol Blood Transplant. 2008 Jan;15(1 Supp):79-83.

    Grupp SA, Frangoul H, Wall D, Pulsipher MA, Levine JE, Schultz KR. Use of G-CSF in Matched Sibling Donor Pediatric Allogeneic Transplantation: A Consensus Statement from the Children's Oncology Group (COG) Transplant Discipline Committee and Pediatric Blood and Marrow Transplant Consortium (PBMTC) Executive Committee. Pediatr Blood Cancer. 2006 Apr;46(4):414-21.

     

    Schultz KR, Miklos DB, Fowler D, Cooke K,  Shizuru J, Emmanuel E, Holler E, Ferrara J, Shulman H, Lee SJ, Martin P, Filipovich AH, Flowers MED, Weisdorf D, Couriel D, Lachenbruch PA, Mittleman B, Vogelsang GB15, Pavletic SZ Towards Biomarkers For Chronic Graft Versus Host Disease: NIH Consensus Development Project On Criteria For Clinical Trials In Chronic Graft-Versus-Host Disease: III Biomarker Working Group Report  Biol Blood Marrow Transplant 2006 Feb;12(2):126-137.

     

    Jastaniah WA, Alessandri AJ, Reid GSD, Schultz KR HLA-DM expression is elevated in ETV6-AML1 translocation positive pediatric acute lymphoblastic leukemia Leukemia Res 2005 Sep 24.

     

    Reid GS, She K, Terrett L, Food MR, Trudeau JD, Schultz KR. CpG stimulation of precursor B lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells towards a Th1 response. Blood. 2005 105:3641-7.

     

    Shier LR, Schultz KR, Imren S, Regan J, Issekutz A, Sadek I, Gilman A, Panzarella T, Eaves CJ, Couban S. Differential Effects of G-CSF on Marrow and Blood-Derived Hematopoietic and Immune Cell Populations in Healthy Human Donors. Biol Blood Marrow Transplantation St ;10(9):624-34,2004.
     
    Schultz KR, Reid G. The Unique Biology and Characteristics of TEL-AML1 (ETV6-CBFA2) Acute Lymphoblastic Leukemia: Potential Therapeutic Approaches. ASCO Educational Book (In press), 2004.
     
    Reid GSD, Terrett L, Allessandri A, Grubb S, Stork L, Seibel N, Gaynon P, Schultz KR. Altered Patterns of T Cell Cytokine Production Induced by Relapsed Pre-B ALL Cells/ :eil Res 2-3'27(12):1135-42.
     
    Schultz KR, Su WN, Hsiao C-C, Jevon G, Bader S, Gilman AL. Chloroquine Prevention Of Murine MHC Disparate Acute Graft-Versus-Host Disease Correlates With Inhibition Of Spleenic Response To CpG Oligodeoxynucleotides And Alterations In T Cell Cytokine Production, Biol Blood Marrow Transplant 8(12):648-55, 2002.
      
    Alessandri AJ, Reid GS, Bader SA, Massing BG, Sorensen PH, Schultz KR. ETV6 (TEL)-AML1 pre-B acute lymphoblastic leukaemia cells are associated with a distinct antigen-presenting phenotype. Br J Haematol. 116:266-72, 2002.
     
    Reid G, Bharya S and Schultz KR. Phosphoinositide-dependent and -independent natural cell killing of pre-B acute lymphoblastic leukemia cells by IL-2 activated NK cells and NK-92ci Clin Exp Immunol. 129:265-271, 2002. 

    Grants
    Honours & Awards

    Geoffrey L. Hammond Lectureship Award, CFRI Member Recognition Awards, 2013
    NIH/NIAID – U54 grant – 2009-2014
    CIHR Biomarkers in Chronic GVHD grant – 2009-2014
    St. Baldrick’s Foundation Grant – 2009-2011
    NIHLBI/NIC Grant – 2006-2011
    CIHR/Wyeth Clinical Research Chair in Transplantation – 2003-2008



    Research Group Members
    Sabine Ivison – Research Associate, Schultz Lab
    Amina Karaminia - Lab technician, Schultz Lab
    Dr. Nina Rolf - Postdoctoral Oncology Research Fellow, Schultz Lab
    Jacob Rozmus – Postdoctoral Oncology Research Fellow, Schultz Lab
    Peter Subrt – Research Coordinator
    Clinical Research Group:
    Dr. Mason Bond
    Dr. John Wu
    Dr. David Dix
    Dr. Caron Strahlendorf
    Dr. Rod Rassekh
    Dr. Chris Fryer
    Dr. Jeff Davis
    Dr. Juliette Hukin
    Dr. Sheila Prichard
    Dr. Paul Rogers
    Dr. Poul Sorensen
    Ruth Milner
    Colleen Fitzgerald – Clinical Research Manager
    • Jessica Davis – CRA
    • Valla Sahraei - CRA
    Nita Takeuchi - Senior Research Associate, Clinical Research
    • Stephanie Badour - CRA
    • Martina Barbour - CRA
    • Fatima Dharsee - CRA
    • Mary-Joan Galvez - CRA
    • Joanne Shinde - CRA
    • Buffy Menjou - CRA