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Dr Xiaoyan Jiang — MD, PhD

Distinguished Scientist

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Laboratory Contact

Josephine Leung

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

Education:
MD, Shanghai Second Medical University
PhD, Molecular Biology, McGill University

Open Positions:

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

  • Molecular and cellular mechanisms of oncogenes and tumor suppressor genes in the development of leukemia
  • Gene regulation
  • Leukemic stem cell biology
  • Basic and translational leukemia research
  • Proteomics

The overall goal of my research program is to understand the molecular mechanisms of gene regulation and the cellular functions of oncogenes and tumor suppressor genes in the development of human leukemia. The ultimate objective is to identify molecules and pathways that will lead to new, rationally designed, more effective, and less toxic molecularly targeted therapies.

My research objectives are currently focused on delineating the normal functions and transforming properties of a novel oncogene, Ahi-1/AHI-1 (Abelson helper integration site 1). Ahi-1 is a recently identified gene that is commonly activated by provirus insertional mutagenesis, possibly in cooperation with other oncogenes (v-abl and Myc) or with a tumor suppressor gene (NF1), in different types of murine leukemias and lymphomas. Ahi-1 is unique in its possession of a SH3 domain, multiple SH3 binding sites and multiple WD40-repeat domains, suggesting that it has novel signaling activities. Interestingly, in leukemias involving Ahi-1 mutations, truncated Ahi-1/viral fused transcripts are produced, including splice variants in which the SH3 domain is deleted. We have recently demonstrated that Ahi-1/AHI-1 transcript levels are normally down-regulated during both early murine and human hematopoietic cell differentiation and are highly deregulated in human leukemic cells, particularly in highly enriched populations of BCR-ABL+ leukemic stem cells (lin-CD34+CD38-) from patients with chronic myeloid leukemia (CML) where levels of BCR-ABL transcripts are also elevated. We are now further characterizing the functions of Ahi-1 and its isoforms during normal mouse development and during early stages of normal hematopoietic cell differentiation and examining the biological changes of human AHI-1 and its isoforms in human leukemic stem/progenitors cells.

We have recently developed two important new models of BCR-ABL-mediated leukemia in mice. These allow the development of disease from a cell with stem cell properties to be followed over a period of 2-4 months, thus recreating a pathogenesis that more closely resembles the emergence of human chronic phase CML. Using these new models, we investigate the leukemogenic consequences of deregulated expression of different Ahi-1/AHI-1 isoforms alone and in concert with other oncogenes and tumor suppressor genes in the development of leukemia in vivo and the resulting altered factor-dependence or skewed or blocked ability to differentiate in vitro. The transforming properties of Ahi-1/AHI-1 are further evaluated by suppression of Ahi-1/AHI-1 (or other co-operating genes) expression in vitro and in vivo through virus-mediated RNA interference.

Another objective of my research is to understand the biological functions of Ahi-1/AHI-1 as a modular molecule that is likely to mediate specific protein-protein interactions to affect novel signaling pathways. Gene expression profiling and proteomic approaches have been applied to identify and characterize Ahi-1/AHI-1 interacting proteins involved in regulation of normal and leukemic stem/progenitor cell proliferation, self-renewal and differentiation.

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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

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Dr Min Chen

PhD
Research Associate
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Rachel Yuanshen Huang

Postdoctoral Fellow

Josephine Leung

Msc
Cancer Research Technologist
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Leon Hanyang Lin

Graduate Student
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Will Xiaohu Liu

Graduate Student
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Vanessa Porter

Graduate Student
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Katharina Rothe

Postdoctoral Fellow
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Dr. Jiechuang Su

PhD
Postdoctoral Fellow
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Kelly Turner

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Ryan Yen

Graduate Student
Vancouver, BC --  22 October 2013 -- Amy Yu - Terry Fox Laboratory (Photo: BC Cancer Agency)

Amy Yu

PMP
Research Projects Manager