Wang, Yemin

Wang, Yemin

PhD

Academic Rank(s): Adjunct Professor, Pathology and Laboratory Medicine, UBC | Staff Scientist, Department of Molecular Oncology, BC Cancer

Affiliation(s): BC Cancer Research Centre, Vancouver Coastal Health Research Institute

Research and Scholarly Interests: Cancer

Clinical Interests:

Short Bio
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Dr. Wang obtained his undergraduate degree in Biology (2001) and master degree in Botany (2003) from Nanjing University in China. He completed his PhD degree in Experimental Medicine at the University of British Columbia in 2009, studying the roles of ING family proteins in melanoma pathogenesis. He then pursued postdoctoral studies at the Fred Hutchison Cancer Research Centre in Seattle, exploring the role of microRNAs in DNA damaging response. In 2012, he joined the Ovarian Cancer Research Program (OVCARE) directed by Dr. David Huntsman at BC Cancer as fellows of Canadian Institute of Health Research and Michael Smith Foundation for Health Research to study how genetic mutations in microRNA biogenesis gene DICER1 drive cancer development. Dr. Wang is currently a staff scientist in the Department of Molecular Oncology, BC Cancer, overseeing the animal research core for the OVCARE team. His lab at the Vancouver Coastal Health Research Institute is currently focusing on addressing how abnormality in SWI/SNF chromatin complex drives cancer development in lineage-specific manner as well as identifying therapeutic vulnerabilities in SWI/SNF-deficient cancers.

 

Academic
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Academic Background

  • Research Associate, University of British Columbia, Vancouver BC (2015-2018)
  • Postdoctoral Fellow (Cancer Genetics), University of British Columbia, Vancouver BC (2012-2015)
  • Postdoctoral Fellow (Cancer Biology), Fred Hutchinson Cancer Research Centre, Seattle WA (2009-2011)
  • Ph.D. (Experimental Medicine), University of British Columbia, Canada (2009)
  • M.Sc. (Botany), Nanjing University, China, 2003
  • BSc. (Biology). Nanjing University, China, 2001

Awards and Recognition

  • North Family Health Research Award. VGH & UBC foundation and OVCARE (2020-2023)
  • UBC Science Co-op Supervisor Recognition Award, UBC (2019)
  • Jeremy Jass Prize for Research Excellence in Pathology (2016), Journal of Pathology (2017)
  • Travel Award, The 6th Canadian Conference on Ovarian Cancer Research (2014)
  • Postdoctoral fellowship, Michael Smith Foundation for Health Research (2012-2014)
  • Postdoctoral fellowship, Canadian Institute of Health Research (2010-2013)
  • AACR-Sanofi-Aventis Scholar-in-Training Award, AACR (2010)
  • Trainee Rising Star, Vancouver Coast Health Research Institute (2008)
  • Terry Fox Foundation PhD Studentship, National Cancer Institute of Canada (2007-2009)
  • PhD Student Travel Award, National Cancer Institute of Canada (2007)
  • Roman M. Babicki Fellowship in Medical Res, University of British Columbia (2006-2007)

Publications

Link to Dr. Yemin Wang’s Google Scholar Profile: https://scholar.google.ca/citations?hl=en&user=sHB0yaMAAAAJ&view_op=list_works&gmla=AJsN-F7k3dDGNaTW01R3-F5qbHtfrns12XFYEV8ClfmUCSVcZRzQQ5zvzuIENcS8jLTRTNVobK9R6l0GKCPW9olT3NwyyoN6pkvTxL2k3rlhKikRtR0ICzw

Selected Publications

  • Karnezis AN, Chen SY, Chow C, Yang W, Hendricks WPD, Ramos P, Briones N, Mes-Masson AM, Bosse T, Gilks CB, Trent JM, Weissman B, Huntsman DG, Wang Y. Re-assigning the histologic identities of COV434 and TOV-112D ovarian cancer cell lines. Gynecol Oncol. 2021 Feb: 160(2):568-578. doi:10.1016/j.ygyno.2020.12.004. Epub ahead of print. 2020 Dec 13PMID: 33328126.
  • Wang Y*, Tao VL, Shin CY, Salamanca C, Chen SY, Chow C, Köbel M, Ben-Neriah S, Farnell D, Steidl C, Mcalpine JN, Gilks CB, Huntsman DG. Establishment and characterization of VOA1066 cells: An undifferentiated endometrial carcinoma cell line. PLoS One. 2020 Oct 14;15(10):e0240412. doi:10.1371/journal.pone.0240412. PMID: 33052929; PMCID: PMC7556492. *co-senior
  • Wang Y, Hoang L, Ji JX, Huntsman DG. SWI/SNF Complex Mutations in Gynecologic Cancers: Molecular Mechanisms and Models. Annu Rev Pathol. 2020 Jan 24;15:467-492. doi:10.1146/annurev-pathmechdis-012418-012917. PMID: 31977292; PMCID: PMC6986318.
  • Karnezis AN*, Wang Y*, Keul J, Tessier-Cloutier B, Magrill J, Kommoss S, Senz J, Yang W, Proctor L, Schmidt D, Clement PB, Gilks CB, Huntsman DG, Kommoss F. DICER1 and FOXL2 Mutation Status Correlates With Clinicopathologic Features in Ovarian Sertoli-Leydig Cell Tumors. Am J Surg Pathol. 2019 May;43(5):628-638. doi:10.1097/PAS.0000000000001232. PMID: 30986800. *co-1st author
  • Wang Y*, Chen SY, Colborne S, Lambert G, Shin CY, Santos ND, Orlando KA, Lang JD, Hendricks WPD, Bally MB, Karnezis AN, Hass R, Underhill TM, Morin GB, Trent JM, Weissman BE, Huntsman DG. Histone Deacetylase Inhibitors Synergize with Catalytic Inhibitors of EZH2 to Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic Type. Mol Cancer Ther. 2018 Dec;17(12):2767-2779. doi: 10.1158/1535-7163.MCT-18-0348. Epub 2018 Sep 19. PMID: 30232145; PMCID: PMC6279577. * co-senior author
  • Wang Y*, Karnezis AN*, Magrill J, Tessier-Cloutier B, Lum A, Senz J, Gilks CB, McCluggage WG, Huntsman DG, Kommoss F. DICER1 hot-spot mutations in ovarian gynandroblastoma. *co-1st author Histopathology. 2018 Aug;73(2):306-313. doi:10.1111/his.13630. Epub 2018 Jun 5. PMID: 29660837.
  • Wang Y, Chen SY, Karnezis AN, Colborne S, Santos ND, Lang JD, Hendricks WP, Orlando KA, Yap D, Kommoss F, Bally MB, Morin GB, Trent JM, Weissman BE, Huntsman DG. The histone methyltransferase EZH2 is a therapeutic target in small cell carcinoma of the ovary, hypercalcaemic type. J Pathol. 2017 Jul;242(3):371-383. doi: 10.1002/path.4912. Epub 2017 Jun 2. PMID: 28444909; PMCID: PMC6857704.
  • Wang Y, Chen J, Yang W, Mo F, Senz J, Yap D, Anglesio MS, Gilks B, Morin GB, Huntsman DG. The oncogenic roles of DICER1 RNase IIIb domain mutations in ovarian Sertoli-Leydig cell tumors. Neoplasia. 2015 Aug;17(8):650-60. doi:10.1016/j.neo.2015.08.003. PMID: 26408257; PMCID: PMC4674484.
  • Karnezis AN*, Wang Y*, Ramos P, Hendricks WP, Oliva E, D’Angelo E, Prat J, Nucci MR, Nielsen TO, Chow C, Leung S, Kommoss F, Kommoss S, Silva A, Ronnett BM, Rabban JT, Bowtell DD, Weissman BE, Trent JM, Gilks CB, Huntsman DG. Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type. J Pathol. 2016 Feb;238(3):389-400. doi: 10.1002/path.4633. Epub 2015 Dec 21. PMID: 26356327; PMCID: PMC4832362. *co-1st author
  • Wang Y*, Huang JW, Castella M, Huntsman DG, Taniguchi T. p53 is positively regulated by miR-542-3p. Cancer Res. 2014 Jun 15;74(12):3218-27. doi:10.1158/0008-5472.CAN-13-1706. Epub 2014 Apr 24. PMID: 24762395; PMCID:PMC4058365. * co-senior author
  • Wang Y, Taniguchi T. MicroRNAs and DNA damage response: implications for cancer therapy. Cell Cycle. 2013 Jan 1;12(1):32-42. doi: 10.4161/cc.23051. Epub 2012 Dec 19. PMID: 23255103; PMCID: PMC3570514.
  • Wang Y, Huang JW, Calses P, Kemp CJ, Taniguchi T. MiR-96 downregulates REV1 and RAD51 to promote cellular sensitivity to cisplatin and PARP inhibition. Cancer Res. 2012 Aug 15;72(16):4037-46. doi: 10.1158/0008-5472.CAN-12-0103. Epub 2012 Jul 3. PMID: 22761336; PMCID: PMC3421071.
  • Wang Y, Huang JW, Li M, Cavenee WK, Mitchell PS, Zhou X, Tewari M, Furnari FB, Taniguchi T. MicroRNA-138 modulates DNA damage response by repressing histone H2AX expression. Mol Cancer Res. 2011 Aug;9(8):1100-11. doi:10.1158/1541-7786.MCR-11-0007. Epub 2011 Jun 21. PMID: 21693595; PMCID:PMC3157593.
Research
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Research Interest

I have a strong interest in understanding the gynecological cancer biology and identifying novel therapeutic targets and strategies for gynecological cancer. Currently I am focusing utilizing the latest molecular and cellular biology techniques as well as various model systems to investigate how genetic abnormalities drive oncogenesis and discovering vulnerabilities of gynecologic cancers with mutations in the SWI/SNF chromatin remodeling complex. I am also interested in applying functional genomics in uncovering drug resistance mechanisms and novel targets in refractory gynecologic cancers.

Research Topics

  • Ovarian and endometrial cancer
  • Cancer cell of origin
  • Cancer models
  • Therapeutic vulnerability
  • Genomics
  • Oncogenic signaling
  • Cancer metabolism

Research Program

Recent next-generation sequencing efforts have discovered that mutations in genes encoding subunits of Mating Type SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes are present in ~25% of all human cancers, ranking it among the most highly mutated protein complexes in cancer. The SWI/SNF complexes are evolutionarily conserved multi-subunit protein complexes that interact with histones and transcription factors. They are composed of 10 to 15 subunits with many possible combinations of subunits, resulting in the presence of numerous distinct sub-complexes in a single cell. All these SWI/SNF complexes include a catalytic ATPase subunit (mutually exclusive SMARCA4/BRG1 or SMARCA2/BRM) and complex-specific subunits, such as ARID1A and ARID1B that are unique to canonical SWI/SNF complex. Although some SWI/SNF proteins have been recognized as critical regulators of cell differentiation and tumorigenesis, the contribution of various SWI/SNF complexes to normal and cancer development remains largely unexplored due to the complexity of the complex.

Studies from the past decade have identified gynecologic cancer, particularly ovarian and endometrial cancers, as great models to study the roles of SWI/SNF complexes in tumorigenesis. SWI/SNF mutations can occur at different stages of gynecologic cancer development and may function as either a driver event, a transformation-permissive event or a progression event. These includes a) inactivating mutations of SMARCA4, occur as a germline event and function as a

classic tumor suppressor and key driver in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT); b) ARID1A inactivating mutations occur as a transformation-permissive event in the development of endometriosis-associated ovarian and endometrial cancers; and c) inactivation of SMARCA4, SMARCB1 mutations or ARID1A/ARID1B dual inactivating mutations in dedifferentiated cancer (DDC) of ovary and endometrium as cancer progression events. However, the context-specific roles of SWI/SNF mutations in the initiation and progression of ovarian and endometrial cancers is far from being fully understood. Since most SWI/SNF-mutant cancers are highly aggressive and most of these genetic alterations result in protein loss that is not directly targetable, identifying druggable vulnerabilities specific to SWI/SNF deficiencies remains an unmet clinical need.

My research will center around these unaddressed questions and identify mechanisms driving the development of ovarian and endometrial cancer. We will also identify novel targetable candidates for therapeutic development for SWI/SNF-mutant cancer. In addition, we will also utilize functional genomics approaches to identify epigenetic and metabolic alterations that drive the development of drug resistance to treatment in SWI/SNF-mutant cancer. Our research will develop or repurpose existing drugs or drug candidates for biology-informed treatment of ovarian and endometrial cancers.

Clinical Service

Current Projects In My Lab Include

Teaching
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Teaching Interest

  • Cancer origin and modeling
  • Chromatin remodeling and cancer development