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Youwen Zhou, MD, University of British Columbia, Vancouver, BC. Sezary syndrome (SS) is a severe type of skin lymphoma, a cancer derived from T lymphocytes in the skin. Patients typically develop extensive red skin rash and swollen lymph glands, and suffer from intense uncontrollable itchiness of the entire skin surface. There is no treatment at present. Therefore, the patients die shortly after disease onset. The patient’s blood stream contains the hall mark cancer cells, called Sezary cells. These cells have the highly unusual structure, resembling the appearance of the brain. Compared with normal T lymphocytes, the Sezary cells are resistant to programmed cell death and can produce abnormal sets of inflammation controlling molecules called cytokines. However, the molecular mechanism of these bahavioural and molecular aberrations in the Sezary cells remains unclear. Clues from our preliminary research lead us to hypothesize that lack of a chromatin organizer protein, SATB1, is responsible for many of these abnormalities. In this project, we will test this hypothesis. First, we will use specialized molecular tools such as retroviral mediated gene transfer, to restore SATB1 production in Sezary cells. Then we will perform a large number of cellular and molecular tests to find out if the Sezary cell abnormalities are normalized. If these abnormalities are corrected by such manipulations of the SATB1 gene, it may be possible to develop a therapy for Sezary syndrome using a similar strategy in the future. Peer-Reviewed Publications Supported by the Canadian Dermatology Foundation 1. Dai D, Makretsov N, Campos E, Martinka M, Huang C, Zhou, Y, Huntsman D, and Li G. Increased expression of integrin linked kinase correlates with melanoma invasion. Clinical Cancer Research 2003; 9:4409-4414. 2. Su MW, Dorocicz I, Degawska V, Voss N, Ho V, Li G, Gascoyne R and Zhou, Y. Aberrant Expression of T-plastin gene in Sezary Cells. Cancer Research 2003; 63:7122- 7127. 3. Zhou, Y, Dai D, Martinka M, Su M, Zhang Y, Campos E, Dorocicz I, Tang L, Huntsman D, Nelson C, Ho, V, Li G. Osteopontin expression correlates with melanoma invasion. J Invest Dermatol 2005; 124(5):1044-52. 4. Tang, L, Dai, D, Martinka, M., Su, MW, Zhang, Y, Li, G and Zhou, Y Aberrant Expression of CTHRC1 in human cancers. Clinical Cancer Research 2006; 12:3716-3722 5. Ringrose A, Zhou Y, Pang E, Zhou L, Lin AE-J, Sheng G, Li XJ, Weng A, Su M-W, Pittelkow MR and Jiang X. Evidence for an Oncogenic Role of AHI-1 in Sezary Syndrome, a Leukemic Variant of Human Cutaneous T-cell Lymphomas. Leukemia 2006; 20:1593-601 6. Liang, Y., Yang, S., Zhou, Y., Cui, J., Ren, Y., Chen, J., Fan, X., Sun, L., Xiao, F., Gao, M., Fang, Q., Xu, S., Huang, W., and Zhang, X. Evidence for two susceptibility loci on Chromosome 22q12 and 6p21-p22 in generalized vitiligo families. J Invest Dermatol 2007; 127(11):2552-57 7. Tang, L., Huang C, Su, MW, Zhang, Y, Ip, W, Martinka, M, and Zhou, Y. Endothelin 3 autocrine pathway in metastatic melanoma. J. Cutaneous Med. Surg. 2008;12(2):64-70 8. Huang C, Tian J, Tao J, Liu Y, Li Y, Yang L, Zhang J, Li Y, Chen S, Lin N, Shen G, Tu Y, and Zhou Y Endothelin signaling axis activates osteopontin expression through PI3 kinase pathway in A375 melanoma cells. Journal of Dermatological Science. 2008;52:130-134 © 2009 |
