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CIHR Skin Research Training Centre
Affiliated Mentors: Dr. Xiaoyan Jiang
Xiaoyan Jiang, MD, PhD
Senior Scientist
Associate Professor, Medical Genetics, University of British Columbia
Associate Member, Medicine, University of British Columbia
Adjunct Professor, Shanghai Institute of Medical Genetics, Shanghai Jiaotong University
Michael Smith Foundation for Health Research Scholar

Terry Fox Laboratory
BC Cancer Agency
675 West 10th Avenue, 
Vancouver BC
Canada V5Z 1L3
Tel: 604-675-8141
Fax: 604-877-0712
Website: http://www.terryfoxlab.ca/people/XJiang/xiaoyan.aspx
Email: xjiang@bccrc.ca
                                                                                                                    

Education

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

Awards and honors

1990-1991 Max Binz Fellowship, McGill University
1992-1994 Hydro-Quebec Fellowship, McGill 21st Century Fund
1993 Roger Boucher Prize for Excellent Research, Clinical Research Institute of Montreal, McGill University
1997-2000 Travel Awards, American Society of Hematology Conference (4 successive years)
2005-2006 Merit Award, Faculty of Medicine, University of British Columbia
2005-2010 Michael Smith Foundation for Health Research Career Investigator Award
2008-2011 Merit Award, Faculty of Medicine, University of British Columbia

Grant Support

Canadian Institutes of Health Research
Canadian Cancer Society Research Institute
Leukemia & Lymphoma Society of Canada
Canadian Cancer Society
Cancer Research Society
 AB Cancer Foundation
Novartis
Bristol-Myers Squibb

Research interest

My research interests are focused on elucidating the molecular pathway perturbations that cause and sustain human leukemia and lymphomas. The ultimate objective is to identify new, rationally designed, molecularly targeted therapies that will be more effective and less toxic than those presently available. Currently, I am pursuing this interest through two lines of investigation. One is a more basic investigation of the molecular mechanisms by which AHI-1, a novel oncogene and signaling molecule, may contribute to the pathogenesis of a number of human leukemias and lymphomas, including chronic myeloid leukemia (CML) and cutaneous T-cell lymphomas (CTCL). By analyzing perturbations in primary human cells and in overexpression and knockdown models, my research group has recently identified a novel AHI-1-BCR-ABL-JAK2 interaction complex that modulates BCR-ABL transforming activity and tyrosine kinase inhibitor response of CML stem/progenitor cells. Understanding the functions of this interaction complex could lead to the development of new molecularly targeted therapies.

The second line of investigation is a translational research effort to develop improved prognosis indicators and treatments for CML and CTCL. The goals of these studies are to develop new predictive tests and to identify new agents, or combinations of agents, that can effectively eradicate CML stem cells, in collaboration with Drs. D. Forrest and C. Eaves at the BCCA; and to understand the molecular roles of AHI-1, HCK and BIN1 tumor suppressor and their potential clinical applications as biomarkers in human CTCL, in collaboration with Dr. Y. Zhou at the BCCA.

Current lab members

Min Chen (Postdoctoral Fellow)
Kevin Lin (Postdoctoral Fellow)
Sharmin Esmailzadeh (PhD student)
Katharina Rothe (PhD student)
Leon Lin (PhD student)
Will Liu (PhD student)
Yuanshen Huang (PhD student)
Damian Lai (MSc student)
Helena Wang (Research technician) 

Selected recent publications

  1. 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 (March 20 issue, 2013).
  2. Zeng F, 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, Huang SZ & Jiang X. Long-term deregulated human hematopoiesis in goats transplanted in utero with BCR-ABL-transduced Lin-CD34+ cord blood cells. Cell Research (In press).
  3. Liu X, Chen M, Lobo P, An J, Cheng SWG, Moradian A, Morin GB, Van Petegem F & 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.
  4. Landry B, Aliabadi HM, Samuel A, Gul H, X. Jiang, Kutsvh O, and Uludag H. Effective non-viral delivery of siRNA to acute myeloid leukemia cells with lipid-substituted polyethylenimines PLOS One 7, e44997, 2012.
  5. 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.
  6. 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.
  7. Sloma I, Jiang X, Eaves AC, Eaves CJ. Insights into the stem cells of chronic myeloid leukemia. Leukemia 24:1823-1833, 2010.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.  

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