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Dr. Jim Xiang

Dr. Jim Xiang is a Senior Research Scientist at the Saskatchewan Cancer Agency and Professor, Division Of Oncology, College of Medicine, University of Saskatchewan since 1996.

Dr. Xiang received his M.D. at the Shanghai University of Medicine in 1970, and obtained his M.S. in 1983 and his Ph.D. in 1986 at the University Florida.

Location:
Cancer Cluster
Room 4D30.1 Health Science Building
107 Wiggins Road
University of Saskatchewan
Saskatoon, SK S7N 5E5
Phone: 306-966-7039
Email: jim.xiang@saskcancer.ca

Research Activities

Dr. Xiang’s Lab focuses on (i) studying the molecular mechanism regulating CD8+ T cell fate and memory formation, (ii) assessing the critical role of CD4+ T cell help in CD8+ T cell immunity, and (iii) developing novel HER2- and Gag-specific exosome-targeted T cell vaccines for HER2+ breast cancer and HIV-1 patients.

1. Molecular pathways for CD8+ T cell fate and memory: Understanding the molecular pathway controlling CD8+ T cell fate and memory is critically important in vaccine development and immunotherapy. We recently discover that mannose-6 phosphate receptor (M6PR) specific for lytic granule Granzyme-B (GB) plays a critical role controlling T cell fate. M6PRhigh CD8+ T cells die of GB-mediated lethal hit, while M6PRlow ones survive in the contraction. We further elucidate that pro-inflammation cytokine IL-2 induces M6PRhigh CD8+ T cells while pro-survival cytokine IL-7 stimulates M6PRlow ones differentiating into long-term memory T cells. The IL-2-stimutaed strong activation of mTORC1 up-regulates motor protein KIF13A leading delivery of more M6PR onto cell surface of IL-2-activated CD8+ T cells susceptible for GB-mediated killing, and vis-à-vis for the IL-7-stimulated weak mTORC1 activation. We are currently studying the molecular pathway regulating the memory T cell differentiation of IL-7-induced M6PRlow CD8+ T cells.

2. A new concept "Th-APC": A long-standing paradox in cellular immunology concerns the conditional requirement for CD4+ T cells in priming of CD8+ cytotoxic T lymphocyte (CTL)responses. We found that CD4+ Th cells can acquire synapse-composed pMHC I and II and CSM from APCs via trogocytosis, and become Th‐APCs capable of stimulating CD8+ T cell response and memory.Therefore, this new conceptual advance may have great impacts in antitumor and autoimmune responses. We are currently studying molecular mechanisms of CD4+ T cell help in CD8+ T cell immunity and memory.

3. Exosome-targeted T cell-based vaccines: Based upon the new concept of “Th-APC”, we developed CD4+ T cell‐based vaccines using polyclonal CD4+ T cells with uptake of Ag‐specific dendritic cell (DC)-released exosomes (EXO), and demonstrate that the novel vaccine is capable of directly stimulating potent CD8+ CTL effector and memory responses, counteracting CD4+ Tr‐mediated immune suppression, and converting CTL exhaustion via its CD40L signaling activation of mTORC1 pathway in chronic infection. We are currently developing HER-2/neu-specific and HIV-1 Gag-specific exosome-targeted T cell vaccines for treatment of HER-2/neu-positive breast cancer and HIV-1 patients. 

Selected Recent Publications

1. Xie Y, Wang L, Frewald A, Qureshi M, Chen Y and Xiang J. Novel T cell-based vaccine capable of stimulating long-term functional CTL memory against B16 melanoma via CD40L signaling. Cell Mol Immunol. 10: 72-77, 2013.

2. Umeshappa C S, Nanjundappa R, Freywald A and Xiang J. Differential requirements of CD4+ T cell signals for effector cytotoxic T lymphocyte (CTL) priming and functional memory CTL development at higher CD8+ T cell precursor frequency. Immunol 138: 298-306, 2013.

3. Wang L, Xie Y, Ahmed K, Ahmed S, Sami A, Chibbar R, Xu Q, Kane S, Hao S, Mulligan S and Xiang J. Exosomal pMHC-I complexes target T cell-based vaccine to directly stimulate CTL responses leading to antitumor immunity in transgenic FVBneuN and HLA-A2/HER2 mice and eradicating trastuzumab-resistant tumor in athymic nude mice. Breast Cancer Res Treat 140: 273-284, 2013.

4. Wang R, Freywald A, Chen Y, Xu J and Xiang J. Transgene 41BBL-engineered vaccine stimulates potent Gag-specific therapeutic and long-term immunity via priming CD44+CD62LhighIL-7R+ CTLs with up- and down-regulation of anti- and pro-apoptosis genes. Cell Mol Immunol, 12: 456-465, 2015.

5. Ahmed K, Wang L, Griebel P, Mousseau D and Xiang J. Differential expression of mannose-6-phosphate receptor regulates T cell contraction. J Leuk Biol, 98: 313-318, 2015.

6. Zhao T, Tan X, Umeshappa C, Ma H, Gao H, Deng Y, Freywald A and Xiang J. Simulated microgravity promotes cell apoptosis through suppression of Uev1A/TICAM/TRAF/NF-kB-regulated anti-apoptosis and p53/PCNA- and ATM/ATR-Chk1/2-controlled DNA-damage response pathways. J Cell Biochem. 117: 2138-2148, 2016.

7. Xu A, Ye Z, Wu J, Leary S, Li R and Xiang J. Irradiation-induced lymphopenia promotes T cell survival via IL-15 signaling STAT5/Bcl2 pathway and enhances T cell memory via IL-15 activation of FOXO/Eomes memory and ULK1/Atg7 autophage pathways. Cell Bioscience. 6: 30, 2016.

8. Wang R, Xu A, Zhang X, Wu J, Freywald A, Xu J and Xiang J. Novel exosome-targeted T cell-based vaccine counteracts T cell anergy and converts CTL exhaustion in chronic infection via CD40L signaling through the mTORC1 pathway. Cell Mol Immunol, 14: 529-545, 2017.

9. Mu C, Zhang X, Wang L, Xu A, Ahmed A, Pang X, Chibbar R, Freywald A, Huang J, Zhu Y and Xiang J. Enhanced suppression of polyclonal CD8+25+ regulatory T cells via exosomal arming of antigen-specific peptide/MHC complexes. J Leuk Biol. 101: 1221-1231, 2017.

10. Khawaja Ashfaque Ahmed and Xiang J. mTORC1 regulates mannose-6-phosphate receptor and T cell vulnerability to regulatory T cells by controlling kinesin KIF13A. Cell Discovery, 3: 17011, 2017.

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