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Dr Xiaoyan Jiang — MD, PhD

Distinguished Scientist

Laboratory Contact

Josephine Leung

Cancer Research Technologist
  604-675-8000 ext 7740
Overview
Research Interest
Publications
Lab Members
Lab Alumni

Education:
MD, Shanghai Second Medical University
PhD, Division of Experimental Medicine, Faculty of Medicine, McGill University

Open Positions:

Highly qualified trainees are welcome to apply at any time by writing directly to xjiang@bccrc.ca.

  • Basic and translational leukemia research
  • Leukemic stem cell biology
  • Gene regulation
  • Drug resistance
  • Proteomics

The overall goal of my research program is to understand the molecular mechanisms and cellular functions of specific oncogenes, tumor suppressor genes, miRNAs and their target genes in the regulation of the properties of cancer/leukemic stem cells, signal transduction events, initiation and progression of human leukemia and drug resistance. The ultimate objective is to identify molecules and pathways that will lead to new, rationally designed, more effective, and less toxic, personalized molecularly targeted therapies. In particular, we are extremely interested in developing mechanism-based combination therapeutic strategies that can directly target drug-insensitive leukemic stem cells.

My research objectives are currently focused on two lines of investigation. One is basic investigation of the molecular mechanisms of several newly identified cancer driver genes as potential therapeutic targets that contribute to the pathogenesis and drug resistance of a number of human leukemias and lymphomas. By analyzing perturbations in primary human leukemic cells, including patient’s leukemic stem/progenitor cells, by global gene expression profiling, in overexpression and knockdown in vitro and in vivo mouse and patient-derived xenograft models, my research group has recently demonstrated that AHI-1 (Abelson helper integration site-1), a scaffold oncoprotein, is highly deregulated in BCR-ABL+ leukemic stem cells and interacts with multiple kinases and other proteins (BCR-ABL, JAK2, β-catenin, DNM2 and γ-Tubulin, etc) to enhance leukemia-initiating activity and drug-resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). We have also been exploring new, complementary therapeutic strategies that can synergistically target key molecular events active in leukemic stem cells and their associated bone marrow niche, autophagy and the Hedgehog signaling pathway, etc, and have uncovered ILK, ATG4B and several miRNAs/target genes as potential biomarkers and therapeutic targets in CML stem/progenitor cells. Understanding dynamic changes in molecular and signaling events regulated by these critical drivers/networks essential for leukemic stem cell functionality/drug resistance will lead to the development of more effective molecularly targeted therapies, critical especially for patients at high risk of drug resistance and disease progression.

The second line of investigation is a translational research effort in human leukemia, which aims to develop new predictive and prognostic tests and improved treatments for human leukemia, in collaboration with local and global clinical leaders, experts in medicinal chemistry and drug design and large drug companies. We have recently identified several unique features of CML stem/progenitor cells and miRNA/target genes that lead to their intrinsic resistance to TKI therapies and might be expected to predict the responsiveness of patients to TKI therapy. These predictive tests will rapidly identify patients who will not benefit from standard TKI monotherapies so that they may be considered rapidly for transplant-based or novel combination treatments to significantly improve outcomes. We have also been testing new therapeutic agents/inhibitors and combination treatment strategies that can effectively eradicate human leukemic stem cells, using our well-established in vitro and in vivo models.

Chen M, Turhan AG, Ding H, Lin Q, Meng K & Jiang X. Targeting BCR-ABL+ stem/progenitor cells and BCR-ABL-T315I mutant cells by effective inhibition of the BCR-ABL-Tyr177-GRB2 complex. Oncotarget 8: 43662-43677, 2017.  View Abstract

Liu X, Rothe K, Yen R, Fruhstorfer C, Maetzig T, Chen M, Forrest D, Humphries RK & Jiang X. A novel AHI-1-BCR-ABL-DNM2 complex regulates leukemic properties of primitive CML cells through enhanced cellular endocytosis and ROS-mediated autophagy. Leukemia 2017. [Epub ahead of print] View Abstract

Seid-Karbasi P, Ye XC, Zhang AW, Gladish N, Cheng SY, Rothe K, Pilsworth JA, Kang MA, Doolittle N, Jiang X, Stirling PC & Wasserman WW. CuboCube: Student creation of a cancer genetics e-textbook using open-access software for social learning. PLoS Biol 15: e2001192, 2017. View Abstract

Klionsky DJ, Abdelmohsen K,…. Jiang X….. Zorzano A, Susu M Zughaier SM. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 12:1-222, 2016. View Abstract

Lebovitz C, Devorkin L, Bosc D, Rothe K, Singh J, Bally M, Jiang X, Young RN, Lum JJ, Gorski SM. Precision autophagy: will the next wave of selective autophagy markers and specific autophagy inhibitors feed clinical pipelines. Autophagy 3:1949-52, 2015. View Abstract

Landry B, Valencia-Serna J, Gul-Uludağ H, Jiang X, Janowska-Wieczorek A, Brandwein J, Uludag H. Progress in RNAi mediated molecular therapy of acute and chronic myeloid leukemia. Mol. Ther. Nucleic Acids 4:e240. doi: 10.1038/mtna.2015.13, 2015. View Abstract

Huang Y, Su MW, Jiang X (Corresponding author), Zhou Y. Evidence of an oncogenic role of aberrant TOX activation in cutaneous T cell lymphoma. Blood 125:1435-1443, 2015. View Abstract

Esmailzadeh S, Su MW, Zhou Y, Jiang X. BIN1 tumor suppressor regulates Fas/Fas ligand-mediated apoptosis through c-FLIP in cutaneous T-cell Lymphoma. Leukemia 29: 1402-13, 2015. View Abstract

Gul-Uludag H, Valencia-Serna J, Kucharski C, Marquez-Curtis L, Jiang X, Larratt L, Janowska-Wieczorek A and Uludag H. Polymeric nanoparticle-mediated silencing of CD44 receptor in CD34+ acute myeloid leukemia cells. Leukemia Research 38, 1299-1308, 2014. View Abstract

Lin H, Chen M, Rothe K, Lorenzi MV, Woolfson A, Jiang X. Selective JAK2/ABL dual inhibition therapy effectively eliminates TKI-insensitive CML stem/progenitor cells. Oncotarget 2014 5, 8637-8650, 2014. View Abstract

Sahin B, Fife J, Parmar MB, Valencia-Serna J, Gul-Uludağ H, Jiang X, Weinfeld M, Lavasanifar A, Uludağ H. siRNA therapy in cutaneous T-cell lymphoma cells using polymeric carriers. Biomaterials 35, 9382-94, 2014. View Abstract

Huang Y, Litvinov IV, Wang Y, Su MW, Tu P, Jiang X, Kupper TS, Dutz JP, Sasseville D, Zhou Y. Thymocyte selection-associated high mobility group box gene (TOX) is aberrantly over-expressed in mycosis fungoides and correlates with poor prognosis. Oncotarget, 2014. Epub ahead of print View Abstract

Jiang X. Distinguishing CML LSCs from HSCs using CD26. Blood 123(25):3851-2, 2014 View Abstract

Rothe K, Lin H , Lin K, Leung A, Wang HM, Malekesmaeili M, Brinkman RR, Forrest DL, Gorski S, Jiang X. The core autophagy protein ATG4B is a potential biomarker and therapeutic target in CML stem/progenitor cells. Blood 123: 3622-34, 2014. View Abstract

Sloma I, Beer PA, Saw KM, Chan M, Leung D, Raghuram K, Brimacombe C, Johnston B, Lambie K, Forrest DL, Jiang X and Eaves CJ. Genotypic and functional diversity of phenotypically defined primitive hematopoietic cells in patients with chronic myeloid leukemia. Exp Hematol 41: 837-47, 2013. View Abstract

Valencia-Serna J, Gul-Uludag H, Mahdipoor P, Jiang X and Uludag H. Investigating siRNA delivery to chronic myeloid leukemia K562 cells with lipophilic polymers for therapeutic BCR-ABL down-regulation. J Controlled Release 172: 495-503, 2013. View Abstract

Jardon MA, Rothe K, Bortnik S, Vezenkov L, Jiang X, Young RN, Lum JJ, Gorski SM. Autophagy: From structure to metabolism to therapeutic regulation. Autophagy 12: 2180-2182, 2013. View Abstract

Chen M, Gallipoli P, DeGeer D, Sloma I, Forrest DL, Chan M, Lai D, Jorgenson H, Ringrose A, Wang HM, Lambie K, Nakamoto H, Saw KM, Turhan A, Arlinghaus R, Barnett MJ, Eaves A, Eaves C, Holyoake TL and Jiang X. Targeting primitive chronic myeloid leukemia cells by effective inhibition of a new AHI-1-BCR-ABL-JAK2 complex. J Natl Cancer Inst 105: 405-423, 2013. View Abstract

Zeng F, Huang SZ, Chen MJ, Gong ZJ, Baldwin D, Qian H, Yan JB, Wang J, Chen X, Xiao YP, Chalandon Y, Ringrose A, Ren ZR, Eaves A, Eaves C & Jiang X. Long-term deregulated human hematopoiesis in goats transplanted in utero with BCR-ABL-transduced Lin-CD34+ cord blood cells. Cell Research 23: 859-862, 2013. View Abstract

Valencia-Serna J, Gul-Uludag H, Tang T, Jiang X and Uludag H. Investigating siRNA delivery to chronic myeloid leukemia K562 cells with lipophilic polymers for therapeutic BCR-ABL down-regulation. J Controlled Release 10: 495-503, 2013. View Abstract

Sloma I, Beer PA, Saw KM, Chan M, Leung D, Raghuram K, Brimacombe C, Johnston B, Lambie K, Forrest DL, Jiang X and Eaves CJ. Genotypic and functional diversity of phenotypically defined primitive hematopoietic cells in patients with chronic myeloid leukemia. Exp Hematology 41: 837-847, 2013. View Abstract

Jardon MA, Rothe K, Bortnik S, Vezenkov L, Jiang X, Young RN, Lum JJ, Gorski SM. Autophagy: From structure to metabolism to therapeutic regulation. Autophagy 12: 1-3, 2013. View Abstract

Landry B, Aliabadi HM, Samuel A, Gul H, Jiang X, Kutsvh O, Uludag H. Effective non-viral delivery of siRNA to acute myeloid leukemia cells with lipid-substituted polyethylenimines  PLoS One 7, e44997, 2012. View Abstract

Liu X, Chen M, Lobo P, An J, Cheng SWG, Moradian A, Morin GB, Van Petegem F and Jiang X. Molecular and structural characterization of the SH3 domain of AHI-1 in regulation of cellular resistance of BCR-ABL+ chronic myeloid leukemia cells to tyrosine kinase inhibitors. Proteomics 12: 2094-2106, 2012.View Abstract

Esmailzadeh S, Jiang X. AHI-1: a novel signaling protein and potential therapeutic target in human leukemia and brain disorders. Oncotarget 12: 918-934, 2011. View Abstract

Wang Y, Su M, Zhou LL, Tu P, Zhang X, Jiang X,  Zhou Y.  Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription. Blood 117:3826-35, 2011. View Abstract

Sloma I, Jiang X, Eaves AC, Eaves CJ.  Insights into the stem cells of chronic myeloid leukemia. Leukemia  24:1823-1833, 2010. View Abstract

Grant H, Jiang X, Stebbing J, Foroni L, Craddock C, Griffiths M, Clark RE, O’Brien    S, Khorashad JS, Gerrard G, Wang L, Irving JAE, Wang M, Karran L, Dyer MJS, Forrest D, Page K, Eaves CJ, Woolfson A. Analysis of BCR-ABL1 tyrosine kinase domain mutational spectra in primitive chronic myeloid leukemia cells suggests a unique mutator phenotype. Leukemia 10: 1817-1821, 2010. View Abstract

Jiang X (Corresponding author), Forrest D, Nicolini F, Turhan A, Guilhot J, Yip C, Holyoake T, Jorgensen H, Lambie K, Saw KM, Pang E, Vukovic R, Lehn P, Ringrose A, Yu M, Brinkman RR, Smith C, Eaves A and Eaves C. Properties of CD34+ CML stem/progenitor cells that correlate with clinical response to imatinib mesylate. Blood 116: 2112-2121, 2010. View Abstract

Xiang P, Lo C, Argiropoulos B, Lai CB, Rouhi A, Imren S, Jiang X, Mager D, Humphries RK. Identification of E74-like factor 1 (ELF1) as a transcriptional regulator of the Hox cofactor MEIS1. Exp Hematol 38:798-808, 2010. View Abstract

Rogers SL, Zhao Y, Jiang X, Eaves CJ, Mager DL and Rouhi A. Expression of the leukemic prognostic marker CD7 is linked to epigenetic modification in chronic myeloid leukemia. Mol Cancer 7: 41, 2010. View Abstract

Kennah E, Ringrose A, Zhou LL, Esmailzadeh S, Qian H, Su MW, Zhou Y, Jiang X.  Identification of tyrosine kinase, HCK, and  tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells.  Blood 113 (19): 4646-55, 2009.  View Abstract

Forrest DL, Jiang X, Eaves CJ & Smith CL. An approach to the management of chronic myeloid leukemia in British Columbia. Curr Oncol 15: 48-55, 2008.  View Article

Jiang X, Zhao Y, Forrest D, Smith C, Eaves A and Eaves C.  Stem Cell Biomarkers in Chronic Myeloid Leukemia.  Disease Markers 24:201-216, 2008.  View Abstract

Sheng G, Xu X, Lin Y-F, Wang C-E, Rong J, Cheng D, Peng J, Jiang X, Li S-H & Li X-J. Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice. J Clin Invest 118: 2785-2795, 2008.  View Article
       
Zhou LL, Zhao Y, Ringrose A, DeGeer D, Kennah E, Lin AEJ, Sheng G, Li X-J, Turhan A & Jiang X. AH1-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells.  J Exp Med 205: 2657-2671, 2008.  View Article

Jiang X, Saw KM, Eaves A, & Eaves C. Instability of BCR-ABL gene in primary and cultured chronic myeloid leukemia stem cells. J  Natl Cancer Inst 99 (9): 680-93, 2007. View Abstract

Jiang X, Smith C, Eaves A, & Eaves C. The challenges of targeting chronic myeloid leukemia stem cells. Clin Lymphoma Myeloma 7 Suppl 2: S71-80, 2007.  View Abstract

Jiang X, Zhao Y, Smith C, Gasparetto M, Turhan A, Eaves A, & Eaves C. Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies. Leukemia 21 (5): 926-35, 2007.  View Abstract

Jorgensen HG, Copland M, Allan EK, Jiang X, Eaves A, Eaves C, & Holyoake TL. Intermittent exposure of  primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate. Clin Cancer Res 12 (2): 626-33, 2006. View Article

Ringrose A, Zhou Y, Pang E, Zhou L, Lin AE, Sheng G, Li XJ, Weng A, Su MW, Pittelkow MR, & Jiang X. Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas. Leukemia 20 (9): 1593-601, 2006.  View Article

Zeng F, Chen MJ, Baldwin DA, Gong ZJ, Yan JB, Qian H, Wang J, Jiang X, Ren ZR, Sun D, & Huang SZ. Multiorgan engraftment and differentiation of human cord blood CD34+ Lin- cells in goats assessed by gene expression profiling. Proc Natl Acad Sci USA 103 (20): 7801-6, 2006.  View Article

Chalandon Y, Jiang X, Christ O, Loutet S, Thanopoulou E, Eaves A, & Eaves C. BCR-ABL-transduced human cord blood cells produce abnormal populations in immunodeficient mice. Leukemia 19 (3): 442-8, 2005. View Article

Eisterer W, Jiang X, Christ O, Glimm H, Lee KH, Pang E, Lambie K, Shaw G, Holyoake TL, Petzer AL, Auewarakul C, Barnett MJ,  Eaves CJ, & Eaves AC. Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a  model of the human disease. Leukemia 19 (3): 435-41, 2005.  View Article

Chalandon Y, Jiang X, Loutet S, Eaves AC, & Eaves CJ. Growth autonomy and lineage switching in BCR-ABL-transduced human cord  blood cells depend on different functional domains of BCR-ABL. Leukemia 18 (5): 1006-12, 2004.  View Abstract

Jiang X, Zhao Y, Chan WY, Vercauteren S, Pang E, Kennedy S, Nicolini F, Eaves A, & Eaves C. Deregulated expression in Ph+  human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia. Blood 103 (10): 3897-904,  2004.  View Abstract

Eaves C, Jiang X, Eisterer W, Chalandon Y, Porada G, Zanjani E, & Eaves A. New models to investigate mechanisms of disease genesis from primitive BCR-ABL(+) hematopoietic cells. Ann N Y Acad Sci 996: 1-9, 2003. View Abstract

Jiang X, Stuible M, Chalandon Y, Li A, Chan WY, Eisterer W, Krystal G, Eaves A, & Eaves C. Evidence for a positive role of SHIP in the BCR-ABL-mediated transformation of primitive murine hematopoietic cells and in human chronic myeloid leukemia. Blood 102 (8): 2976-84, 2003. View Abstract

Jorgensen HG, Allan EK, Jiang X, Liakopoulou E, Richmond L, Eaves CJ, Eaves AC, & Holyoake TL. Stage-specific alterations in serum levels of G-CSF in chronic myeloid leukaemia. Leukemia 17 (7): 1430-2, 2003. View Abstract

Chalandon Y, Jiang X, Hazlewood G, Loutet S, Conneally E, Eaves A, & Eaves C. Modulation of p210(BCR-ABL) activity in   transduced primary human hematopoietic cells controls lineage programming. Blood 99 (9): 3197-204, 2002.  View Abstract

Eisterer W, Jiang X, Bachelot T, Pawliuk R, Abramovich C, Leboulch P, Hogge D, & Eaves C. Unfulfilled promise of endostatin in a  gene therapy-xenotransplant model of human acute lymphocytic leukemia. Mol Ther 5 (4): 352-9, 2002.  View Abstract

Holyoake TL, Jiang X, Drummond MW, Eaves AC, & Eaves CJ. Elucidating critical mechanisms of deregulated stem cell turnover in the chronic phase of chronic myeloid leukemia. Leukemia 16 (4): 549-58, 2002.  View Abstract

Jiang X, Ng E, Yip C, Eisterer W, Chalandon Y, Stuible M, Eaves A, & Eaves CJ. Primitive interleukin 3 null hematopoietic cells  transduced with BCR-ABL show accelerated loss after culture of factor-independence in vitro and leukemogenic activity in vivo. Blood    100 (10): 3731-40, 2002.  View Abstract

Jiang X, Hanna Z, Kaouass M, Girard L, & Jolicoeur P. Ahi-1, a novel gene encoding a modular protein with WD40-repeat and SH3 domains, is targeted by the Ahi-1 and Mis-2 provirus integrations. J Virol 76 (18): 9046-59, 2002.   View Abstract

Holyoake TL, Jiang X, Jorgensen HG, Graham S, Alcorn MJ, Laird C, Eaves AC, & Eaves CJ. Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with up-regulation of
expression of interleukin-3. Blood 97 (3): 720-8, 2001.  View Abstract

Jiang X, Fujisaki T, Nicolini F, Berger M, Holyoake T, Eisterer W, Eaves C, & Eaves A. Autonomous multi-lineage differentiation in vitro of primitive CD34+ cells from patients with chronic myeloid leukemia. Leukemia 14 (6): 1112-21, 2000.  View Abstract

Holyoake T, Jiang X, Eaves C, & Eaves A. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood 94 (6): 2056-64, 1999.  View Abstract

Jiang X, Lopez A, Holyoake T, Eaves A, & Eaves C. Autocrine production and action of IL-3 and granulocyte colony-stimulating factor  in chronic myeloid leukemia. Proc Natl Acad Sci U S A 96 (22): 12804-9, 1999.  View Abstract

Dr Min Chen

PhD
Research Associate

Josephine Leung

Msc
Cancer Research Technologist

Xiaojia Niu

Visiting Graduate Student

Vanessa Porter

Graduate Student

Dr. Katharina Rothe

PhD
Postdoctoral Fellow

Kelly Turner

Graduate Student

Jason Wang

Graduate Student

Ryan Yen

Graduate Student

Amy Yu

PMP
Research Projects Manager

Jiang Lab - 2011

 

Jiang lab - 2010

 

Jiang Lab - 2009

 

 

 

 

Rachel Huang, PhD student, 2010-2016 / Postdoctoral Fellow, 2016-2017

Will (Xiaohu) Liu, PhD student, 2010-2016

Leon (Hanyang) Lin, PhD student, 2010-2016

Damian Lai, MSc student, 2012-2015

Sharmin Esmailzadeh, PhD student, 2008-2014

Donna DeGeer, MSc student, 2007-2010

Erin Kennah, MSc student, 2006-2008

Sean Kennedy, MSc student, 2004-2007