Christopher Paige
Script error: No such module "Draft topics".
Script error: No such module "AfC topic".== 2010 CSI: Hardy Cinader Award recipient ==
- Named in honor of Dr. Hardy Cinader who was one of the immunologists that "founded" immunology in Canada in the 1960s
- This award is awarded to an Immunologist working in Canada who is an exceptional researcher and also has something "extra"
Education:[edit]
1979: Ph.D. in Immunology at Cornell University
1980-1987: A member of the Basel Institute for Immunology in Switzerland
1988-1989: Joined the Ontario Cancer institute
1990: Director of the Arthritis and Autoimmunity Research Centre and the Director of Research at The Wellesley Hospital.
1998: Vice-president in Ontario Cancer, vice-president in research of the University Health Network.
- Professor in the Departments of Medical Biophysics and Immunology at the University of Toronto.
Research Interests[edit]
Cancer Diagnosis and Therapy, Cancer Mechanisms and Models, Stem Cells and Regenerative Medicine
Research Synopsis[edit]
B Cell Development
B lymphocytes produce antibodies and present antigens. They are essential components of the immune response. Failure to regulate the growth, development, and response of B cells can lead to malignancy, immunodeficiency and autoimmunity. Our research efforts are directed towards a better understanding of the process of B cell commitment and the events that allow progression along the B cell pathway. Cellular, biochemical, and molecular techniques are utilized to achieve our research aims.
Understanding biochemical and cellular checkpoints during lymphoid development
We have developed a number of in vitro assays over the years that allow for the careful examination of the stages of B lineage development from multipotent stem cells to fully functional, antibody secreting, plasma cells. We have identified a number of key features and mechanisms of action that mark transitions between stages and defined checkpoints that can result in positive and negative selection. Amongst our current interest are: The role of the peptide, HK1 (a member of the tackykinin family) in regulating early events in the B lineage pool; a potential mechanism for abrogating IL7 responsiveness based on downstream induction of SOCS proteins; and a novel role for IL21 in accelerating B cell development. Out interest in these projects is driven not only by the desire to understand the role of these molecules in normal development but also because the aberrant regulation of any of these can have direct consequences in immune regulated disease.
Immune System and Disease.
Increased understanding of the immune response and, in particular, the biochemical pathways that regulate immunity provide the basis for renewed efforts to develop cancer vaccines. We have developed a syngeneic cell-based anti-leukemia murine model focused on the expression of IL-12 derived from LV transductions. In that work we showed that syngeneic leukemia cells expressing IL-12 can induce protective, long-lasting, and specific immunity. Of interest for clinical application, we also demonstrated that as few as 0.5% of the leukemia cells have to express IL-12 to achieve immunity, as long as each cell produces IL-12 above a certain threshold. Once initiated, the immune response it is effective against all of the leukemia cells, including those that do not express IL-12. Using in vivo and in vitro culture systems we are determining the cells required both to initiate immunity and target and kill leukemia cells. This work is being extended to solid tumours as well. In addition, these techniques are now being modified using primary human leukemia cell blasts from AML, ALL, CML, and CLL in experiments which form the basis for subsequent human clinical trials.
Research achievements[edit]
Publications: 223
Citations: 13,377
Selected recent publications:
- Paige C, Plasencia-Fernandez I, Kume M, Papalampropoulou-Tsiridou M, Lorenzo LE, David ET, He L, Mejia GL, Driskill C, Ferrini F, Feldhaus AL, Garcia-Martinez LF, Akopian AN, De Koninck Y, Dussor G, Price TJ. A Female-Specific Role for Calcitonin Gene-Related Peptide (CGRP) in Rodent Pain Models. J Neurosci. 2022 Mar 9;42(10):1930-1944. doi: 10.1523/JNEUROSCI.1137-21.2022. Epub 2022 Jan 20. PMID: 35058371; PMCID: PMC8916765.
- Sacher AG, St Paul M, Paige CJ, Ohashi PS. Cytotoxic CD4+ T Cells in Bladder Cancer-A New License to Kill. Cancer Cell. 2020 Jul 13;38(1):28-30. doi: 10.1016/j.ccell.2020.06.013. PMID: 32663467.
- Morelli AE, Sumpter TL, Rojas-Canales DM, Bandyopadhyay M, Chen Z, Tkacheva O, Shufesky WJ, Wallace CT, Watkins SC, Berger A, Paige CJ, Falo LD Jr, Larregina AT. Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells. Cell Rep. 2020 Mar 10;30(10):3448-3465.e8. doi: 10.1016/j.celrep.2020.02.054. PMID: 32160549; PMCID: PMC7169378.
- Berger A, Colpitts SJ, Seabrook MSS, Furlonger CL, Bendix MB, Moreau JM, McKillop WM, Medin JA, Paige CJ. Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model. J Immunother Cancer. 2019 Dec 19;7(1):355. doi: 10.1186/s40425-019-0777-8. PMID: 31856922; PMCID: PMC6924073.
- Shikatani EA, Besla R, Ensan S, Upadhye A, Khyzha N, Li A, Emoto T, Chiu F, Degousee N, Moreau JM, Perry HM, Thayaparan D, Cheng HS, Pacheco S, Smyth D, Noyan H, Zavitz CCJ, Bauer CMT, Hilgendorf I, Libby P, Swirski FK, Gommerman JL, Fish JE, Stampfli MR, Cybulsky MI, Rubin BB, Paige CJ, Bender TP, McNamara CA, Husain M, Robbins CS. c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells. Cell Rep. 2019 May 21;27(8):2304-2312.e6. doi: 10.1016/j.celrep.2019.04.090. PMID: 31116977.
- Cen SY, Moreau JM, Furlonger C, Berger A, Paige CJ. Differential regulation of IgA+ B cells in vitro by stromal cells from distinctive anatomical compartments. J Leukoc Biol. 2019 Mar;105(3):507-518. doi: 10.1002/JLB.1A0517-172RR. Epub 2018 Dec 21. PMID: 30576006.
- Schaefer N, Zheng F, van Brederode J, Berger A, Leacock S, Hirata H, Paige CJ, Harvey RJ, Alzheimer C, Villmann C. Functional Consequences of the Postnatal Switch From Neonatal to Mutant Adult Glycine Receptor α1 Subunits in the Shaky Mouse Model of Startle Disease. Front Mol Neurosci. 2018 May 24;11:167. doi: 10.3389/fnmol.2018.00167. PMID: 29910711; PMCID: PMC5992992.
- Li M, Kouzmina E, McCusker M, Rodin D, Boutros PC, Paige CJ, Rodin G. Cytokines and depression in cancer patients and caregivers. Neuropsychiatr Dis Treat. 2017 Nov 28;13:2903-2911. doi: 10.2147/NDT.S144774. PMID: 29238195; PMCID: PMC5713706.
- Moreau JM, Cen S, Berger A, Furlonger C, Paige CJ. Bone marrow basophils provide survival signals to immature B cells in vitro but are dispensable in vivo. PLoS One. 2017 Sep 28;12(9):e0185509. doi: 10.1371/journal.pone.0185509. PMID: 28957409; PMCID: PMC5619841.
- Schaefer N, Berger A, van Brederode J, Zheng F, Zhang Y, Leacock S, Littau L, Jablonka S, Malhotra S, Topf M, Winter F, Davydova D, Lynch JW, Paige CJ, Alzheimer C, Harvey RJ, Villmann C. Disruption of a Structurally Important Extracellular Element in the Glycine Receptor Leads to Decreased Synaptic Integration and Signaling Resulting in Severe Startle Disease. J Neurosci. 2017 Aug 16;37(33):7948-7961. doi: 10.1523/JNEUROSCI.0009-17.2017. Epub 2017 Jul 19. PMID: 28724750; PMCID: PMC5559766.
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