Pamela Ohashi

Pamela Sumiko Ohashi, PhD, FRSC is a Canadian medical researcher. She is Co-Director of the Campbell Family Institute for Breast Cancer Research, Director of the Cancer Immune Therapy Program at the Princess Margaret Cancer Centre and a Professor at the University of Toronto.

Pamela Ohashi
Alma materUniversity of Toronto
Scientific career
FieldsCancer Immunotherapy
ThesisMolecular analysis and expression of T cell antigen receptor genes
Doctoral advisorTak Wah Mak

Education

Ohashi obtained her BSc in Biology from York University in 1982.[1]

She received her PhD from the University of Toronto Department of Immunology in 1988. Her graduate supervisor was Tak Wah Mak.[1][2]

Scientific career

In her undergraduate studies at York University, Ohashi did wet lab research in the laboratories of James Friesen, John Heddle, and Ron Pearlman.[1]

Following an interest in immunology, she pursued a PhD in Tak Mak’s lab at Princess Margaret Hospital, graduating in 1988.[1][2]

Ohashi conducted post-doctoral research with Rolf Zinkernagel and Hans Hengartner at the University of Zurich until 1991.[1][2][3]

In 1992, Ohashi established a research program at Princess Margaret Hospital, where she is now a Senior Scientist.[4]

Ohashi is a Professor in the Departments of Medical Biophysics and Immunology at the University of Toronto.[3][5]

At Princess Margaret Cancer Centre, Ohashi is Co-Director of the Campbell Family Institute for Breast Cancer Research, and Director of the Cancer Immune Therapy Program.

Her achievements resulted in her appointment as Canada Research Chair in Autoimmunity and Tumour Immunity.[6]

Research

Ohashi undertook a fourth year undergraduate research project with Dr Ron Pearlman on genomic analysis of Tetrahymena repetitive sequences.[1][7]

In her PhD research on T Cell Receptors (TCR), Ohashi found that expression of beta chain cDNA was essential for the expression of a functional TCR/CD3 complex on the cell surface. This complex was shown to be responsible for mediating signal transduction via specific stimulation of the TCR of Jurkat cells.[8] She created mouse lines with transgenic T cells expressing rearranged TCR genes and showed evidence supporting the model that commitment to certain T cell lineages occurs prior to the rearrangement of the composite receptor genes.[9]

Ohashi’s early work focused on understanding basic mechanisms of T cell tolerance versus activation. She was a pioneer in showing conclusively that thymocyte selection is based on an affinity/avidity model.[2][10][11] She was also the first to demonstrate that self-reactive peripheral T cells can remain in a naïve state in the T cell repertoire; a concept that has become widely known as T cell “ignorance”.[2][12]  

This has led to Ohashi’s current approach in understanding how to manipulate and improve cytotoxic T cells to enhance the immune response against cancer.[1] She demonstrated that ignorant T cells could be activated against tumours and showed that altering the molecular programming of dendritic cells can alter the steady state and promote T cell activation in the absence of conventional dendritic cell maturation signals.[2][13][14][15] This is a novel way to break T cell tolerance in vivo and provides important insights into potential mechanisms of autoimmunity.[2][16]

Ohashi directs the translational program of Princess Margaret Cancer Centre's Cancer Immune Therapy Program, designing and running clinical trials using novel immune therapeutic approaches to treat cancer patients.[4] Ohashi was key investigator on the first Phase I clinical trial to use adoptive cell therapy for ovarian cancer.[17]

Awards and distinctions

2018: Robert L Noble Prize[3][18]

2015: Member of the Board of Directors of the Society for Immunotherapy of Cancer[3][19]

2014: Hardy Cinader Award[2]

2011: CSI Investigator Award[20]

2006: Fellow of the Royal Society of Canada[21]

2003: Pharmingen Investigator Award[22]

1998: William E. Rawls Award[1][2]

Chair of the AACR Immunotherapy Steering committee[3]

Founding Senior Editor: Cancer Immunology Research[3]

References
  1. "Alumni Spotlight - Pamela Ohashi". York University.
  2. "Cinader Award - Pamela Ohashi" (PDF). Canadian Society for Immunology.
  3. "Governance - Pamela S. Ohashi, PhD, FRSC". American Association for Cancer Research.
  4. "Researcher - Pamela S Ohashi". University Health Network.
  5. "Faculty - Pamela S Ohashi". Department of Immunology.
  6. Government of Canada, Industry Canada (2012-11-29). "Canada Research Chairs". www.chairs-chaires.gc.ca. Retrieved 2020-06-11.
  7. Brunk, Clifford F.; Tsao, Smiley G. S.; Diamond, Catherine H.; Ohashi, Pamela S.; Tsao, Nora N. G.; Pearlman, Ronald E. (1982-09-01). "Reorganization of unique and repetitive sequences during nuclear development in Tetrahymena thermophila". Canadian Journal of Biochemistry. 60 (9): 847–853. doi:10.1139/o82-107. ISSN 0008-4018. PMID 7172094.
  8. Ohashi, Pamela S.; Mak, Tak W.; Van den Elsen, Peter; Yanagi, Yusuke; Yoshikai, Yasunobu; Calman, Andrew F.; Terhorst, Cox; Stobo, John D.; Weiss, Arthur (August 1985). "Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer". Nature. 316 (6029): 606–609. doi:10.1038/316606a0. ISSN 0028-0836. PMID 4033759. S2CID 4329876.
  9. Ohashi, Pamela S.; Wallace, Valerie A.; Broughton, Heather; Ohashi, Cara T.; Ferrick, David A.; Jost, Veronica; Mak, Tak W.; Hengartner, Hans; Pircher, Hanspeter (1990). "Specific deletion of the J-Cδ locus in murine α/β T cell clones and studies using transgenic mice". European Journal of Immunology. 20 (3): 517–522. doi:10.1002/eji.1830200309. ISSN 1521-4141. PMID 2318248.
  10. Ohashi, Pamela S.; Pircher, Hanspeter; Bürki, Kurt; Zinkernagel, Rolf M.; Hengartner, Hans (August 1990). "Distinct sequence of negative or positive selection implied by thymocyte T-cell receptor densities". Nature. 346 (6287): 861–863. doi:10.1038/346861a0. ISSN 0028-0836. PMID 1975427. S2CID 4241143.
  11. Kawai, Kazuhiro; Ohashi, Pamela S. (March 1995). "Immunological function of a defined T-cell population tolerized to low-affinity self antigens". Nature. 374 (6517): 68–69. doi:10.1038/374068a0. ISSN 0028-0836. PMID 7870174. S2CID 4325817.
  12. Ohashi, Pamela S.; Oehen, Stephan; Buerki, Kurt; Pircher, Hanspeter; Ohashi, Cara T.; Odermatt, Bernhard; Malissen, Bernard; Zinkernagel, Rolf M.; Hengartner, Hans (April 1991). "Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice". Cell. 65 (2): 305–317. doi:10.1016/0092-8674(91)90164-T. PMID 1901764. S2CID 8293666.
  13. Speiser, Daniel E.; Miranda, Renata; Zakarian, Arsen; Bachmann, Martin F.; McKall-Faienza, Kim; Odermatt, Bernhard; Hanahan, Douglas; Zinkernagel, Rolf M.; Ohashi, Pamela S. (1997-08-29). "Self Antigens Expressed by Solid Tumors Do Not Efficiently Stimulate Naive or Activated T Cells: Implications for Immunotherapy". Journal of Experimental Medicine. 186 (5): 645–653. doi:10.1084/jem.186.5.645. ISSN 0022-1007. PMC 2199023. PMID 9271580.
  14. Nguyen, Linh T.; Elford, Alisha R.; Murakami, Kiichi; Garza, Kristine M.; Schoenberger, Stephen P.; Odermatt, Bernhard; Speiser, Daniel E.; Ohashi, Pamela S. (2002-02-18). "Tumor Growth Enhances Cross-Presentation Leading to Limited T Cell Activation without Tolerance". Journal of Experimental Medicine. 195 (4): 423–435. doi:10.1084/jem.20010032. ISSN 1540-9538. PMC 2193619. PMID 11854356.
  15. Dissanayake, Dilan; Hall, Håkan; Berg-Brown, Nancy; Elford, Alisha R; Hamilton, Sara R; Murakami, Kiichi; Deluca, Leslie Summers; Gommerman, Jennifer L; Ohashi, Pamela S (December 2011). "Nuclear factor-κB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells". Nature Medicine. 17 (12): 1663–1667. doi:10.1038/nm.2556. ISSN 1078-8956. PMID 22081022. S2CID 1245361.
  16. Johnson, Dylan J.; Ohashi, Pamela S. (May 2013). "Molecular programming of steady-state dendritic cells: impact on autoimmunity and tumor immune surveillance: Molecular programming of steady-state dendritic cells". Annals of the New York Academy of Sciences. 1284 (1): 46–51. doi:10.1111/nyas.12114. PMID 23651192.
  17. "Clinical Trial Ohashi". BioCanRx. 2016-10-12. Retrieved 2020-06-11.
  18. "CCS honours Canada's best cancer researchers - Canadian Cancer Society". www.cancer.ca. Retrieved 2020-06-11.
  19. "SITC Expands Global Reach, Elects Key Opinion Leaders to the Board - Society for Immunotherapy of Cancer (SITC)". www.sitcancer.org. Retrieved 2020-06-11.
  20. "Award Winners". Canadian Society for Immunology.
  21. "Fellows | Page 89 | The Royal Society of Canada". rsc-src.ca. Retrieved 2020-06-11.
  22. "AAI-PharMingen Investigator Award". American Association of Immunology.
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