Molecular Medicine Laboratory & Chieng Genomics Centre
(Director: Youwen Zhou, MD, PhD)
Name:
Academic Titles:
Zhou, Youwen
1. Associate Professor
2. Chieng Genomics Centre Director
and Senior Scientist
Degrees / Designations:
MD, PhD, FRCPC
Primary Area of Research:
Biomarker discovery and clinical
applications for cancers and skin
diseases
Secondary Area(s) of Research: Drug development for cancer and
skin inflammation
Email:
ywzhou@interchange.ubc.ca
Phone:
604-875-4747
Fax:
604-873-9919
Assistant:
Bay Gumboc
Assistant Phone:
604-875-4747
Mailing Address:
835 West 10th Ave
Vancouver, BC V6Z 4E8, Canada
Clinical Appointments
Skin oncologist, British Columbia
Cancer Agency
Staff dermatologist, Vancouver
General Hospital
Research Areas
The focus of the Molecular Medicine Lab is on biomarker discovery and application in the
diagnosis, treatment and therapeutic development for cancers and skin diseases
Summary
Genomic tools such as transcriptional profiling and whole genome SNP scanning are used to
identify disease-specific gene markers for common skin diseases such as skin lymphoma,
melanoma, vitiligo, rosacea and hyperhidrosis. These markers are then evaluated for their
significance as diagnostic markers or therapeutic targets.
Current Projects
1. Development of diagnostic and therapeutic antibodies for cancer and skin diseases:
Multiple biomarkers discovered from this laboratory (patent pending) show superior sensitivity
and specificity for the diagnosis and prognostication of melanoma and skin lymphoma compared
with the currently available tools. Therefore, one of the main research areas of the lab is to
develop robust monoclonal antibodies so that these markers can be translated into clinical use. In
addition, several antibodies against cancer antigens also possess cancer growth inhibition and
anti-inflammation properties. These antibodies will serve as early leads for the development of
therapeutic antibodies against metastatic cancers and human inflammatory diseases.
2. Cutaneous T cell lymphoma and Sezary syndrome:
Sezary syndrome is an aggressive form of cutaneous T cell lymphoma (CTCL) that has high
mortality. This lab has identified unique and novel biomarkers for the malignant cells. At
present, these markers are being developed into diagnostic tools (patent pending), and unique
research tools for large scale preparation of CTCL cells so that previously impractical integrated
genomic analysis on these cells can now take place.
3. Identification and functional characterization of genetic skin diseases using next
generation sequencing technologies:
Many human diseases, including most of skin diseases have origins in the genetic
characteristics of the affected individuals. The maturation of the large scale and high-fidelity
genomic sequencing and whole genome mapping techniques has made it possible to
systematically identify these genetic traits. The Molecular Medicine Lab, and the associated
Chieng Genomics Centre, is studying several such genetic skin diseases, including vitiligo and
hyperhidrosis, with the aim of understanding their genetic basis.
Selected Publications
1. Zhang Y, Wang Y, Yu R, Huang R, Su M, Dutz J, Martinka M, Xiao C, Zhang X, Zheng Z,
and Zhou Y. Molecular markers of early stage mycosis fungoides. J Invest Dermatol. 2011
(In press)
2. Zhu K, Lv YM, Yin X, Wang Z, He S, Cheng H, Hu D, Zhang Z, Li Y, Zuo X, Zhou Y,
Yang S, Zhang XJ and Zhang F. Psoriasis Stepwise Regression Analysis of MHC Loci
Identifies Shared Genetic Variants with Vitiligo. PLOS One (Published on line, July 2011)
3. Liu Y, Lv Y, Yang X, Ren Y, Zhang X, Guo B, Li M, Gao M, Zuo X, Zhou F, Chen G, Yin
X, Sun L, Zheng X, Zhang S, Liu J, Zhou Y, Jiang T, Zhang Q, Zhang P, Li Y, Wang J,
Wang J, Yang H, Yang S, Li R, and Zhang, X. Exome sequencing identifies NCSTN
mutations in inversa acne (hidradenitis suppurativa) J Invest Dermatol. 2011
Jul;131(7):1570-2
4. Wang, Y, Su Mw, Zhou, LL, Tu, P Zhang, XJ, Jiang, X and Zhou, Y. Deficiency of SATB1
expression in Sézary cells causes apoptosis resistance by regulating FasL/CD95L
transcription. Blood 2011 Apr 7;117(14):3826-35
5. Quan, C, Ren, Y, Xiang, L, Sun, L, et al, Zhou, Y, and Zhang X-J. Genome-wide association
study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nature Genetics, 2010.
42: 614-8
6. Wang, Y, Jiang, H, Dai, et al and Zhou, Y. Alpha 1 antichymotrypsin is aberrantly expressed
during melanoma progression and predicts poor survival for patients with metastatic
melanoma. Pigment Cell Mel Res 2010; 23:575-8
7. Xu, S., Zhou, Y et al and Zhang, X-J. Platelet-derived growth factor receptor alpha gene
mutations in vitiligo vulgaris. Acta Dermatol Venereol. 2010. 90: 131-5.
8. Wei S, Zhang T, Zhou Y, Zhang B, Zhu H, Li J, Huang Z, Deng L and Zhang X-J Fine
Mapping of the Disseminated Superficial Porokeratosis Locus to a 2.7Mb Region on 18p11.3
Clin Exp Dermatol. 2010. 35: 664-7
9. Bissonnette R, Chen G, Bolduc C, Maari C, Li B, Lyle M, Tang L, Wanggui Y, Webster J
and Zhou Y. Efficacy and safety of topical WBI1001 in the treatment of atopic dermatitis:
results from a phase IIa randomized placebo controlled clinical trial. Arch Dermatol, 2010;
146:446-9
10. Kennah E, Ringrose A, Zhou LL, Esmailzadeh S, Qian H, Su M-w, Zhou Y, and 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, 2009; 113:4646-55.
11. Ren, Y, Yang S, Xu, S , Gao M, Huang W, Gao T,Fang Q, Quan C, Zhang C, Sun L, Liang
Y, Han J, Wang Z, Zhang F, Zhou Y, Liu J, Zhang X. Genetic Variation of Promoter
Sequence Modulates XBP1 Expression and Genetic Risk for Vitiligo. PLoS Genetics. 2009;
5: e1000523
12. 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. J Dermatol Sci. 2008;52:130-134.
13. 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
14. Zhang J, Adam D, Stebbing E, Gerbrandt J, Lui H, Shapiro J, and Zhou Y. Efficacy of a daycare program in the treatment of psoriasis. J. Cutaneous Med. Surg. 2008;12:211-216
15. Tao J, Huang C, Yu N, Wu Y., Liu Y, Li Y, Tian J, Yang L, Zhang J, Li J, Zhou, Y and Tu
Y. Olmsted syndrome: a case report and review of literature. Int. J. Dermatol. 2008;47:432437
16. 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 Chinese generalized vitiligo families. J Invest
Dermatol. 2007; 127(11):2552-57
17. Zhang, Y, Tang T, Su, MW, Eisen, D, Zloty, D, Warshawski, L, and Zhou, Y. Expression of
endothelins and their receptors in non-melanoma skin cancers. J. Cutaneous Med. Surg.
2006; 10 (6): 269-276
18. 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
19. 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
20. 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.
21. 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.
22. 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.
23. Su M, Merz DC, Killeen MT, Zhou, Y, Zheng H, Kramer JM, Hedgecock EM, and Culotti
JG. Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal
tip cells in Caenorhabditis elegans. Development. 2000;127:585-594
24. Zhou,Y, Barnet M, Rivers J. Clinical significance of skin biopsies in the diagnosis and
management of graft-vs-host disease in early postallogeneic bone marrow transplantation.
Archives of Dermatology. 2000;136:717-721
25. Zhou Y, Lee H-S T, Koosheh F, Fujisawa H, Sauder DN, Kondo S. Effects of UVB
irradiation on keratinocyte growth factor and its receptors expression in cultured human
keratinocytes. Exper Dermatol 1996; 5:138-144.
26. Hamelin M, Zhou Y, Su M, Scott I, Culotti JG. Expression of the unc-5 guidance receptor in
the touch neurons of C. elegans steers their axons dorsally. Nature 1993; 364:327-330
27. McAllister WT, Zhou, Y, MacDonald L, Raskin C. Regulation of transcription elongation
and termination. J Cell. Biochem 1993; 147 (15G):223-275
28. MacDonald LE, Zhou Y, McAllister WT. Termination and slippage by bacteriophage T7
RNA polymerase. J Molecular Biol 1993; 87:1030-1047
29. Leung-Hagesteijn C, Spence AM, Stern BD, Zhou, Y, Su M, Hedgecock EM, Culotti JG.
Unc-5, a transmembrane protein with immunoglobulin and thrombospondin type 1 domains,
guides cell and pioneer axon migrations in C. elegansC. Cell 1992; 71:289-299
30. Rodriguez D, Zhou Y, Rodriguez JR, Durbin R, McAllister WT, Esteban M. Regulated
expression of a nuclear gene by T3 RNA polymerase and lac repressor delivered by
recombinant vaccinia viruses. J Virology 1990; 64:4851-4857.
31. Baricos WH, Cortez SL, Le QC, Zhou,Y, Dicarlos RM, O’Connor SE, Shah SV. Glomerular
basement membrane degradation by endogenous cystein proteinases in isolated rat glomeruli.
Kidney International 1990; 38:395-401.
32. Zhou Y, Giordano T, Durbin R, McAllister WT. Synthesis of functional messenger RNA in
mammalian cells by bacteriophage T 3 RNA polymerase. Molecular and Cellular Biology
1990; 10:4529-4537.
33. Baricos WH, Zhou, Y, Mason RW, Barrett AJ. Human kidney cathepsons B and L:
characterization and potential role in degradation of glomerular basement membrane.
Biochem J 1988; 252:301-304
34. Baricos WH, Murphy G, Zhou Y, Nguyen HH, Shah SV. Degradation of glomerular
basement membrane by purified mammalian metalloproteinases. Biochemi J 1988; 254:609612.
35. Baricos WH, Zhou,Y, Feurst R, Barrett A, Shah SV. The role of aspartic and cysteine
proteinases in albumin degradation by rat kidney cortical lysosomes. Arch Biochem
Biophysics 1987; 256:687-691
36. Wang YH, Zhang XY, Khan R, Zhou, Y, Huang L-H, Ehrlich M. Methylated DNA-binding
protein from human placenta recognizes specific methylated sites on several prokaryotic
DNAs. Nucleic Acid Res 1986; 14:9843-9860
Honours & Awards
2007
2006
2003
2001
2001
1990-1991
Established Clinician Scientist Award (Vancouver Hospital Foundation)
NSFC Young Investigator Collaborator Award
Young Investigator Award, Canadian Dermatology Foundation
New Opportunity Award, Canada Foundation for Innovation
Young Investigator Award, Banting Research Foundation
Network of Centers of Excellence Postdoctoral Fellowship Award
Research Group Members
Mingwan Su, PhD (Senior research associate)
Lixin Xia, MD (Post-doctoral fellow)
Richard Yu (Master’s student)
Anna Hinek , MD (Dermatology resident)
Rachel Huang, (PhD student)
Katie Belenzney, MD (Dermatology resident)
Magdalene Martinka, MD (Dermatopathology)
Xiaobo Duan, PhD (Senior research associate)