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Xiaowei Chen, PhD

Xiaowei Chen, PhD
About

Assistant Professor

Research Program

Identifying breast cancer causative loci by global DASE profiling
Identifying a highly-aggressive DCIS subgroup
Strategies to identify novel lincRNA gene candidates for breast tumorigenesis

 

Education, Training & Credentials

Educational Background

  • PhD, Nutritional Biochemistry, University of North Carolina at Chapel Hill, 2002
  • MS, Biomedicine, Huazhong University of Science and Technology, 1993
  • BE, Biomedicine, Huazhong University of Science and Technology, 1990

Honors & Awards

  • Anna D. Barker Postdoctoral Award, American Association for Cancer Research, 2004
  • New Investigator Award, American College of Nutrition, 2000
Research Profile

Research Program

Research Interests

Differential allele-specific expression (DASE) and intra-individual tumor heterogeneity

 

  • Global DASE analysis to identify novel coding or no-coding genetic factors for breast cancer development
  • Roles of breast cancer-associated lincRNAs in breast tumor progression and metastasis
  • Intra-individual heterogeneity among pre-malignant/pre-invasive lesions in breast

Lab Overview

Global DASE analysis to identify novel coding or no-coding genetic factors for breast tumorigenesis

We hypothesize that DASE is a functional index for cis-acting variants and pathogenic mutations, and global profiling of DASE in breast cancer precursor tissues can be used to identify novel causative alleles for breast cancer susceptibility. We employed the Illumina® Beadchip for genome-wide allele-specific expression (GWASE) measurements in a set of normal HMEC established from breast cancer patients. We developed two statistical methods, SNP- and gene-based approaches, which allow us to identify 90 and 143 genes with significant DASE>2 (P ≤ 0.01, FDR ≤ 0.05), respectively. Importantly, 34 coding and 26 non-coding candidate loci are identified by both approaches. Ingenuity Pathway Analysis revealed two major interaction networks, which involve a variety of biological functions, including cell death and cell-to-cell signaling. Our study demonstrated that global DASE profiling could be a powerful new approach to identify breast cancer risk alleles. We are currently collaborating with Dr. Richard Katz (CE member) to use BioID system to characterize the roles of these DASE genes in breast cancer development.

 

Identification of breast cancer-associated lincRNA candidates using high-dense SNP arrays

The intergenic portion of the human genome is pervasively transcribed to produce large numbers of long intergenic non-coding RNAs (lincRNAs), which have recently been suggested to regulate a wide array of transcriptional and posttranscriptional processes in both physiological and disease conditions. Results from our previous studies showed that lincRNA genes appear to be less susceptible to copy number variations (CNV) in comparison to coding and other intergenic regions, indicating lincRNAs may be essential for maintaining cell survival. Here, we established a novel genome-wide approach, employing high-density arrays, to globally identifying lincRNA genes whose expression is altered in breast cancers. We hypothesize that the lincRNAs whose expression is frequently altered during malignant transformation likely influence breast tumor progression and thus are new breast cancer candidate genes.

 

Intra-individual heterogeneity among pre-malignant/pre-invasive lesions

The heterogeneity among multiple DCIS lesions within the same patient, also diagnosed with invasive IDC, has not been well evaluated, leaving clinical and research implications of this intra-individual heterogeneity of DCIS yet to be explored. In our recent study, we have clearly demonstrated that intra-individual heterogeneity in multi-lesional DCIS is very common in patients with concurrent diagnoses of IDC. Our results showed that seventy-two percent of the individuals had heterogeneous expression in at least 2 out of 6 IHC markers tested. Furthermore, a subpopulation of DCIS lesions (Subgroup IIb) had a higher Ki-67 index and positive p53 expression, but lower p16 staining intensity, than those in DCIS lesions (Subgroup I) with different molecular subtypes from the adjacent IDC. In comparison to other DCIS subgroups (I or IIa), type IIb DCIS lesions had the same molecular subtypes as the adjacent IDC but not the same subtypes as the adjacent normal terminal duct lobular units (TDLU). Our findings suggested the existence of DCIS subgroups with different degrees of “aggressiveness” (i.e. Subgroup I, indolent DCIS; Subgroup IIb, invasion-prone DCIS). Supported by these novel findings, we hypothesize that the “aggressive” DCIS subgroups which give rise to IDC share the same gene signatures as adjacent IDC, and these gene signatures will not only serve as risk markers to differentiate “indolent” or “invasion-prone” DCIS subpopulations but will also play a role in the DCIS initiation and progression. We are currently collaborating with Dr. Mary Daly (CPC member) to characterize the high-risk DCIS subgroup.

People

Pengtao Jiang, MD, PhD

Postdoctoral Associate

Room: W363
215-214-4286

Carolyn Slater, BS

Technical Specialist

Room: W363
215-214-4286

Li Yueran, MD, PhD

Visiting Scientist

Room: W363
215-214-4286

Hongyu Han, MD, PhD

Visiting Scientist

Room: W363
215-214-4286

Michael Lindy

Undergraduate Student

Room: W363
215-214-4286
Publications

Selected Publications

Pape-Zambito, D., Jiang, Z., Wu, H., Devarajan, K., Slater, C.M., Cai, K.Q., Patchefsky, A., Daly, M.B., and Chen, X. (2014). Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients. PLoS One 9, e100488. PubMed

 

Chen, X., and Anderson, J.J. (2014). Diet and the bone marrow niche for stem cell recruitment. J Bone Miner Res 29, 1041-1042. PubMed

 

Paliwal, A., Temkin, A.M., Kerkel, K., Yale, A., Yotova, I., Drost, N., Lax, S., Nhan-Chang, C.L., Powell, C., Borczuk, A., Aviv, A., Wapner, R., Chen, X., Nagy, P.L., Schork, N., Do, C., Torkamani, A., and Tycko, B. (2013). Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation. PLoS Genet 9, e1003622. PubMed

 

Jiang, Z., Zhou, Y., Devarajan, K., Slater, C.M., Daly, M.B., and Chen, X. (2012). Identifying putative breast cancer-associated long intergenic non-coding RNA loci by high density SNP array analysis. Front Genet 3, 299. PubMed

 

Gao, C., Devarajan, K., Zhou, Y., Slater, C.M., Daly, M.B., and Chen, X. (2012). Identifying breast cancer risk loci by global differential allele-specific expression (DASE) analysis in mammary epithelial transcriptome. BMC Genomics 13, 570. PubMed

 

Brewster, B.L., Rossiello, F., French, J.D., Edwards, S.L., Wong, M., Wronski, A., Whiley, P., Waddell, N., Chen, X., Bove, B., Kconfab, Hopper, J.L., John, E.M., Andrulis, I., Daly, M., Volorio, S., Bernard, L., Peissel, B., Manoukian, S., Barile, M., Pizzamiglio, S., Verderio, P., Spurdle, A.B., Radice, P., Godwin, A.K., Southey, M.C., Brown, M.A., and Peterlongo, P. (2012). Identification of fifteen novel germline variants in the BRCA1 3'UTR reveals a variant in a breast cancer case that introduces a functional miR-103 target site. Hum Mutat 33, 1665-1675. PubMed

 

Chen, X., Weaver, J., Bove, B.A., Vanderveer, L.A., Weil, S.C., Miron, A., Daly, M.B., and Godwin, A.K. (2008). Allelic imbalance in BRCA1 and BRCA2 gene expression is associated with an increased breast cancer risk. Hum Mol Genet 17, 1336-1348. PubMed

 

Chen, X., Truong, T.T., Weaver, J., Bove, B.A., Cattie, K., Armstrong, B.A., Daly, M.B., and Godwin, A.K. (2006). Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and expression. Hum Mutat 27, 427-435. PubMed

 

Chen, X., Arciero, C.A., Wang, C., Broccoli, D., and Godwin, A.K. (2006). BRCC36 is essential for ionizing radiation-induced BRCA1 phosphorylation and nuclear foci formation. Cancer Res 66, 5039-5046. PubMed

 

Schilder, R.J., Sill, M.W., Chen, X., Darcy, K.M., Decesare, S.L., Lewandowski, G., Lee, R.B., Arciero, C.A., Wu, H., and Godwin, A.K. (2005). Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res 11, 5539-5548. PubMed

 

Guo, S., Hakimi, M.A., Baillat, D., Chen, X., Farber, M.J., Klein-Szanto, A.J., Cooch, N.S., Godwin, A.K., and Shiekhattar, R. (2005). Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res 65, 3011-3016. PubMed

 

Dong, Y., Hakimi, M.A., Chen, X., Kumaraswamy, E., Cooch, N.S., Godwin, A.K., and Shiekhattar, R. (2003). Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol Cell 12, 1087-1099. PubMed

Additional Publications

My NCBI