Faculty and Staff Directory
College of Arts and Sciences
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Despite aggressive clinical treatments which include surgical resection, radiation, and chemotherapy, tumor recurrence is essentially universal in cancer patients, which is due, at least in part, to tumor cell heterogeneity. One of the currently prevailing models explaining intratumoral heterogeneity is the Cancer Stem Cell (CSC) hypothesis (Figure 1). According to this model, cancer stem cells (CSCs) represent a subset of a heterogeneous cancer population that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cancer cell types found in a particular cancer sample. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple non-tumorigenic cell types. Convincing evidence indicates that CSCs are inefﬁciently eliminated by current therapeutic treatments and suggests that CSC persistence could be responsible for disease maintenance and/or recurrence. Developing therapeutic interventions that speciﬁcally target CSCs, an appealing strategy for improving cancer treatment, requires an understanding of how CSCs escape normal regulatory mechanisms and become malignant. Our laboratory is utilizing combined molecular, biochemical, genomic and proteomic approaches to dissect signaling pathways in breast cancer stem cells. Interdisciplinary collaborations are established to leverage other expertise in nanotechnology and mathematical modeling to assist understanding the behaviors of CSCs both in vitro and in vivo and develop novel CSC-targeted therapies.
1. Soni M, Patel Y, Markoutsa E., Jie C, Liu S. Xu P and Chen H. Autophagy, Cell Viability
and Chemo-resistance are Regulated by miR-489 in Breast Cancer. Mol. Can. Res. 2018.
(Featured article in the September 2018 issue of Mol. Cancer Res.) [Epub ahead of
2. Patel Y., Soni M., Awgulewitsch A., Kern M., Liu S, Shah N., Singh U.and Chen H. Overexpression of miR-489 derails mammary hierarchy structure and inhibits Her2/neu-induced tumorigenesis. Oncogene. 2018. [Epub ahead of print].
3. Liu S, Lee JS, Jie C, Park M, Patel Y, Soni1 M, Reisman D and Chen H. HER2 overexpression triggers an IL-1α pro-inflammatory circuit to drive tumorigenesis and promote chemotherapy resistance. Cancer Res. 2018, 78:2040-2051.
4. Patel Y, Shah N, Lee JS, Markoutsa E, Jie C, Liu S, Botbyl R, Reisman D2, Xu P and Chen H. A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth. Oncotarget. 2016, 7:18295-308.
5. Liu S, Jin K, Hui Y, Fu J, Jie C, Feng S, Reisman D, Wang Q, Fan D, Sukumar S and Chen H. HOXB7 promotes malignant progression by activating the TGFβ signaling pathway. Cancer Research. 2015, 75:709-19.
6. Tashkandi H, Shah N, Patel Y and H Chen. Identification of new microRNA biomarkers associated with HER2-positive breast cancers. Oncoscience. 2015. 2: 924-929.
7. He H, Altomare D, Ozer U, Xu H, Creek K, Chen H and Xu P. Cancer cell-selective killing polymer/copper combination. Biomater Sci. 2015; 4:115-20.
8. Patel Y, Lee JS, and Chen H. Clinicopathological analysis of miRNA expression in breast cancer tissue by using miRNA in situ hybridization. 2015. JOVE. In press.
9. Shah N. and Chen H. MicroRNAs in pathogenesis of breast cancer: implications in diagnosis and treatment. World J. Clin. Oncol. 2014, 5(2): 48–60.
10. RB KC, Chandrashekaran V, Cheng B, Chen H, Peña MM, Zhang J, Montgomery J, Xu P. Redox Potential Ultrasensitive Nanoparticle for the Targeted Delivery of Camptothecin to HER2-Positive Cancer Cells. Mol Pharm. 2014, 11 (6):1897–1905.
11. Lo, PK and Chen H. Cancer stem cells and cells-of-origin in MMTV-Her2/neu induced mammary tumorigenesis. Oncogene. 2013, 32:1338-40.
12. Lo PK, Lee JS, Chen H, Reisman D, Berger FG and Sukumar. Cytoplasmic mislocalization of overexpressed FOXF1 is associated with the malignancy and metastasis of colorectal adenocarcinomas. Exp Mol Pathol. 2013, 94:262-9.
13. Duan X, Cai L, Lee A, Chen H & Wang Q. Incorporation of azide sugar analogue decrease tumorigenic potential of breast cancer cells by reducing cancer stem cell population. Science China. 2013, 56:1–7.
14. Feng S, Duan X, Lo PK, Liu S, Liu X, Chen H* and Wang Q*. Expansion of breast cancer stem cells with fibrous scaffolds. Integrative Biol. 2013, 5:768-77. (*corresponding author; Highlighted as cover).
15. Liu X, Kanojia D, Lo PK, Wang Q, Wang Q, Nie Q,and Chen H. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy. Scientific Reports. 2013, 3:2473.
16. Lo, P. K., D. Kanojia, X. Liu, U. P. Singh, F. G. Berger, Q. Wang and Chen H. CD49f and CD61 identify Her2/neu-Induced mammary tumor Initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFβ signaling. Oncogene. 2012, 31(21):2614-26.
17. Saha, S, Duan X, Wu L, Lo PK, Chen H*, and Wang Q*. Electrospun Fibrous Scaffolds Promote Breast Cancer Cell Alignment and Epithelial-Mesenchymal Transition. Langmuir 2012, 28(4):2028-34. (*corresponding author).
18. Wang S, Kanojia D, Lo PK, Chandrashekaran V, Duan X, Berger FG, Wang Q and Chen H. Enrichment and selective targeting of cancer stem cells in colorectal cancer cell lines. Human Genetics and Embryology 2012, S2-006.
19. Saha, S, Lo PK, Duan X, Chen H*, and Wang Q*. Breast tumour initiating cell fate is regulated by microenvironmental cues from an extracellular matrix. Integrative Biol. 2012, 4, 897-904. (*corresponding author and top ten most accessed articles in June 2012).
20. Duan X, Li H, Chen H and Q Wang. Discrimination of colon cancer stem cells using noncanonical amino acid. Chem. Commun. 2012, 48, 9035-9037.
21. Wu X, Ellmann S, Rubin E, Gil M, Jin K, Han L, Chen H, Kwon EM, Guo J, Ha HC, and Sukumar S. ADP ribosylation by PARP-1 suppresses HOXB7 transcriptional activity. PLoS One. 2012, 7:e40644.
22. Kanojia D, Zhou W, Zhang J, Jie C, Lo PK, Wang Q and Chen H. Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice. Proteomics. 2012, 12:3407-15.
23. Yu F, Li J, Chen H, Fu, J, Ray S, Huang S, Zheng H and Ai W. Kruppel-like factor 4 (KLF4) is required for self-renewal of cancer stem cells and promotes migration and invasion of mammary cancer cells. Oncogene. 2011, 30:2161-72.
24. Gu Y, Fu J, Lo P, Wang S, Wang Q and Chen H. The effect of B27 supplement on promoting in vitro propagation of Her2/neu-transformed mammary tumorspheres. Journal of Biotech Res. 2011, 3:7-18.
25. Jo H, Lo PK, Li Y, Loison F, Green S, Wang J, Silberstein LE, Ye K, Chen H*, and Luo H*. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination. Proc Natl Acad Sci USA. 2011, 108:6486-91. (*corresponding author and highlighted in Nature Chem. Biol. 2011, 7:340).
26. Kanojia D and Chen H. The microenvironment and breast cancer stem cells. In: Mehmet Gunduz et al (Eds). Breast Cancer Cells / Book 4, ISBN 978-953-307-1332-4. Intech Publisher. 2011. p237-246.
27. Zhang X, Wan G, Mlotshwa S, Vance V, Berger FG, Chen H and Lu X. Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway. Cancer Res. 2010, 70:7176-86.
28. Chen H*, Pimienta G, Gu Y, Kim M-S, Chaerkady R, Gucek M, Cole RN, Sukumar S and Pandey A*. Proteomic phenotype of HER2-expressing mammary epithelial cells using SILAC. Proteomics. 2010, 10:3800-10. (*corresponding author).