The central idea of my research is that appropriate stimulation of the immune system will provide an effective strategy for the treatment and prevention of childhood cancers. Our research, therefore, seeks to understand the influence of the immune system during cancer progression and to use this knowledge to develop approaches to induce therapeutic anti-cancer immune activity. In addition to evaluating the impact of immune responses on established disease, our research seeks to identify the influence of the immune system before cancer is detected. To achieve these goals we use a range of experimental systems, including transgenic mice, adoptive transfer models, human xenograft models, and ex vivo and in vitro analysis of patient samples and human cell lines. It is hoped this broad approach will expedite the development of effective new treatments for children with cancer.
CD47-ligation induced cell death in T-acute lymphoblastic leukemia
Cell Death & Disease
Pascal Leclair, Chi-Chao Liu, Mahdis Monajemi, Gregor S. Reid, Laura M. Sly, Chinten James Lim
Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1ß production
Cell Death & Disease
Anthony C Tang, Seyed M Rahavi, Shan-Yu Fung, Henry Y Lu, Hong Yang, Chinten J Lim, Gregor S Reid, Stuart E Turvey
Cell Cycle-dependent Tumor Engraftment and Migration are Enabled by Aurora A
Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia.
Cancer Immunology, Immunotherapy
Generation of a multi-antigen-directed immune response for durable control of acute lymphoblastic leukemia.
IFN-¿ directly inhibits murine B-cell precursor leukemia-initiating cell proliferation early in life
European Journal of Immunology
Mario Fidanza, Alix E. Seif, Sumin Jo, Amina Kariminia, Nina Rolf, Laura M. Sly, Stephan A. Grupp, Gregor S. D. Reid
alpha-Integrin expression and function modulates presentation of cell surface calreticulin.
Cell death & disease
Liu, C-C and Leclair, P and Monajemi, M and Sly, L M and Reid, G S and Lim, C J
Intravenous immunoglobulin skews macrophages to an anti-inflammatory, IL-10-producing activation state
Journal of Leukocyte Biology
Kozicky, Lisa K. and Zhao, Zheng Yu and Menzies, Susan C. and Fidanza, Mario and Reid, Gregor S. D. and Wilhelmsen, Kevin and Hellman, Judith and Hotte, Naomi and Madsen, Karen L. and Sly, Laura M.
Heterodimer-specific TLR2 stimulation results in divergent functional outcomes in B-cell precursor acute lymphoblastic leukemia
European Journal of Immunology
Rolf, Nina and Kariminia, Amina and Ivison, Sabine and Reid, Gregor S. and Schultz, Kirk R.
Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling
Barrett, D. M. and Seif, A. E. and Carpenito, C. and Teachey, D. T. and Fish, J. D. and June, C. H. and Grupp, S. A. and Reid, G. S. D.
Interferon-gamma-Dependent Infiltration of Human T Cells into Neuroblastoma Tumors In vivo
Clinical Cancer Research
Reid, Gregor S. D. and Shan, Xiaochuan and Coughlin, Christina M. and Lassoued, Wiem and Pawel, Bruce R. and Wexler, Leonard H. and Thiele, Carol J. and Tsokos, Maria and Pinkus, Jack L. and Pinkus, Geraldine S. and Grupp, Stephan A. and Vonderheide, Robert H.
Long-term protection from syngeneic acute lymphoblastic leukemia by CpG ODN-mediated stimulation of innate and adaptive immune responses
Seif, Alix E. and Barrett, David M. and Milone, Michael and Brown, Valerie I. and Grupp, Stephan A. and Reid, Gregor S. D.
Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia and lymphoproliferative disease
Brown, Valerie I. and Seif, Alix E. and Reid, Gregor S. D. and Teachey, David T. and Grupp, Stephan A.
Targeting Notch signaling in autoimmune and lymphoproliferative disease
Teachey, David T. and Seif, Alix E. and Brown, Valerie I. and Bruno, Marlo and Bunte, Ralph M. and Chang, Yueh J. and Choi, John K. and Fish, Jonathan D. and Hall, Junior and Reid, Gregor S. and Ryan, Theresa and Sheen, Cecilia and Zweidler-McKay, Patrick and Grupp, Stephan A.
Detection of WT1-specific T cells in paediatric acute lymphoblastic leukaemia patients in first remission
British Journal of Haematology
Barbaric, Draga and Corthals, Sophie L. and Jastaniah, Wasil A. and Asalanian, Soudabeh and Shimizu, Hiromi and Reid, Gregor S. D. and Schultz, Kirk R.
mTOR inhibitors are synergistic with methotrexate: an effective combination to treat acute lymphoblastic leukemia
Teachey, David T. and Sheen, Cecilia and Hall, Junior and Ryan, Theresa and Brown, Valerie I. and Fish, Jonathan and Reid, Gregor S. D. and Seif, Alix E. and Norris, Robin and Chang, Yueh J. and Carroll, Martin and Grupp, Stephan A.
Altered Toll-like receptor 9 responses in circulating B cells at the onset of extensive chronic graft-versus-host disease
Biology of Blood and Marrow Transplantation
She, Kevin and Gilman, Andrew L. and Aslanian, Soudabeh and Shimizu, Hiromi and Krailo, Mark and Chen, Zhengjia and Reid, Gregor S. and Wall, Donna and Goldman, Fred and Schultz, Kirk R.
In vivo control of acute lymphoblastic leukemia by immunostimulatory CpG oligonucleotides
Fujii, Hisaki and Trudeau, Jacqueline D. and Teachey, David T. and Fish, Jonathan D. and Grupp, Stephan A. and Schultz, Kirk R. and Reid, Gregor S. D.
Differential immune effects mediated by Toll-like receptors stimulation in precursor B-cell acute lymphoblastic leukaemia
British Journal of Haematology
Corthals, SL and Wynne, K and She, K and Shimizu, H and Curman, D and Garbutt, K and Reid, GSD
HLA-DM expression is elevated in ETV6-AML1 translocation-positive pediatric acute lymphoblastic leukemia
Jastaniah, WA and Alessandri, AJ and Reid, GSD and Schultz, KR
CpG stimulation of precursor B-lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells toward a Th1 response
Reid, GSD and She, K and Terrett, L and Food, MR and Trudeau, JD and Schultz, KR
Immune evasion strategies of pediatric precursor-B acute lymphoblastic leukemia after allogeneic bone marrow transplantation - a case study
Barbaric, D and Wynne, K and Aslanian, S and Bond, M and Reid, GSD
The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization
Journal of Immunology
Davidson, DJ and Currie, AJ and Reid, GSD and Bowdish, DME and MacDonald, KL and Ma, RC and Hancock, REW and Speert, DP
Progression of spontaneous autoimmune diabetes is associated with a switch in the killing mechanism used by autoreactive CTL
Qin, HL and Trudeau, JD and Reid, GSD and Lee, IF and Dutz, JP and Santamaria, P and Verchere, CB and Tan, RS
Expression of the adaptor protein BLNK/SLP-65 in childhood acute lymphoblastic leukemia
Imai, C and Ross, ME and Reid, G and Coustan-Smith, E and Schultz, KR and Pui, CH and Downing, JR and Campana, D
Primary immunodeficiency to pneumococcal infection due to a defect in toll-like receptor signaling
Journal of Pediatrics
Currie, AJ and Davidson, DJ and Reid, GSD and Bharya, S and MacDonald, KL and Devon, RS and Speert, DP
Altered patterns of T cell cytokine production induced by relapsed pre-B ALL cells
Reid, GSD and Terrett, L and Alessandri, AJ and Grubb, S and Stork, L and Seibel, N and Gaynon, P and Schultz, KR
ETV6 (TEL)-AML1 pre-B acute lymphoblastic leukaemia cells are associated with a distinct antigen-presenting phenotype
British Journal of Haematology
Alessandri, AJ and Reid, GSD and Bader, SA and Massing, BG and Sorensen, PHB and Schultz, KR
Differential killing of pre-B acute lymphoblastic leukaemia cells by activated NK cells and the NK-92 ci cell line
Clinical and Experimental Immunology
Reid, GSD and Bharya, S and Klingemann, HG and Schultz, KR
TAP expression provides a general method for improving the recognition of malignant cells in vivo
Alimonti, J and Zhang, QJ and Gabathuler, R and Reid, G and Chen, SS and Jefferies, WA
Surrogate antigen processing mediated by TAP-dependent antigenic peptide secretion
Journal of Cell Biology
Gabathuler, R and Alimonti, J and Zhang, QJ and Kolaitis, G and Reid, G and Jefferies, WA
Novel peptide-binding proteins and peptide transport in normal and TAP-deficient microsomes
Marusina, K and Reid, G and Gabathuler, R and Jefferies, W and Monaco, JJ
COMPARISON OF CELL-LINES DEFICIENT IN ANTIGEN PRESENTATION REVEALS A FUNCTIONAL-ROLE FOR TAP-1 ALONE IN ANTIGEN-PROCESSING
Journal of Experimental Medicine
GABATHULER, R and REID, G and KOLAITIS, G and DRISCOLL, J and JEFFERIES, WA
TRANSPORT AND EXPRESSION IN HUMAN MELANOMAS OF A TRANSFERRIN-LIKE GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEIN
Journal of Biological Chemistry
FOOD, MR and ROTHENBERGER, S and GABATHULER, R and HAIDL, ID and REID, G and JEFFERIES, WA
THE ROLE OF THE OVARY AND NUTRITIONAL SIGNALS IN THE REGULATION OF FAT-BODY YOLK PROTEIN GENE-EXPRESSION IN DROSOPHILA-MELANOGASTER
Journal of Insect Physiology
BOWNES, M and REID, G
Immune influence on ALL development. Infection has long been postulated to play a role in the progression of childhood ALL. Using novel models of this disease we are actively identifying the influence of the immune system during a pre-leukemic state on the onset of ALL. Our research indicates that the immune system may exert considerable control over early pre-leukemic cell expansion, but other mechanisms, such as growth factor availability, may also be important. Our long-term goal is to identify the growth constraints on pre-leukemic expansion, understand the influence of infection on these constraints, and use this knowledge to develop targeted strategies to reduce the incidence of primary disease and relapse.
Immune therapy for acute lymphoblastic leukemia (ALL). This research addresses the issue of ALL immunogenicity and the induction of anti-ALL immune activity as a strategy to eradicate residual disease after chemotherapy. Our work has described the ability of immunostimulatory DNA (CpG ODN) treatment both to enhance the immunogenicity of primary human ALL blasts and to stimulate significant anti-ALL immune activity resulting in T cell-mediated protection against disease progression. This work provided the first report of immune-mediated killing of primary human ALL in vivo in the absence of adoptive transfer of lymphocytes or stem cell transplantation, and indicates that toll-like receptor signaling may provide a clinically feasible strategy for augmenting immune responses against ALL. A clinical trial based on this approach is aboout to commence. The next major step in our development of CpG ODN as an immune therapy for ALL will involve the examination of their ability to induce anti-leukemia immune activity after chemotherapy in a spontaneous mouse model of ALL, and to generate ALL-specific T cells against autologous leukemia blasts from patients. By using such models, in which immune tolerance must be overcome, this ongoing work will be the most stringent pre-clinical testing yet of an immune therapy for pediatric leukemia. The goal of these studies is to provide insights that will optimize the clinical application of this approach.Grants
Canadian Institutes of Health Research
Canadian Cancer Society
Leukemia & Lymphoma Society of CanadaResearch Group Members
S.M Reza Rahavi, Doctoral Student
Brenda Tse, Research Coordinator
Arnawaz Kaleem, Technician
Ali Farrokhi, Postdoctoral Fellow