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Home > Organization > Divisions and Independent Research Units > Group for Translational Research > Division of Molecular and Cellular Medicine > Research Projects > Spatiotemporal analysis of transcription regulatory networks in cancer

Spatiotemporal analysis of transcription regulatory networks in cancer

In the process of cancer initiation and progression, various types of cellular stress such as inflammation cause genomic mutations including single nucleotide polymorphisms and copy number variations in oncogenes and tumor suppressors, as well as epigenetic changes, in multiple stages via pre-neoplastic lesions. Since most of the data of human cancer samples were obtained retrospectively from fully-developed tumor tissues, it is hard to predict how and when the mutations were induced, and how alterations to gene expression, genomic mutations and epigenetic modifications lead to the development of these tumors.. By using in vitro carcinogenic system, we aim to clarify how the transcription regulatory network is shifted from normal to cancer mode, and the dynamics of chromatin structure in the carcinogenesis process. By introducing oncogenes and chemically-induced carcinogenic animal models, we have performed spatiotemporal analysis of transcription regulatory networks and signal pathways in the process of tumorigenesis from normal cells to precancerous lesions to malignancy

Clarification of cancer development process is not only important from the viewpoint of basic biology but is also tightly related to the identification and development of biomarkers for the early detection and selection of target molecules for treatment, being a novel strategy for cancer prevention.

Spatiotemporal analysis of transcription regulatory networks in cancer

  1. Basuli D, Tesfay L, Deng Z, Paul B, Yamamoto Y, Ning G, Xian W, McKeon F, Lynch M, Crum CP, Hegde P, Brewer M, Wang X, Miller L, Dyment N, Torti FM, Torti SV. Iron addiction: A novel therapeutic target in ovarian cancer. Oncogene, in press (2017) PMID: 28319068
  2. Yamamoto Y, Wang X, Bertrand D, Kern F, Zhang T, Duleba M, Srivastava S, Khor CC, Hu Y,  Wilson L, Blaszyk H, Rolshud D, The M, Liu J, Howitt BE, Vincent M, Crum CP, Nagarajan N, Ho KY, McKeon F & Xian W. Mutational Spectrum of Barrett’s Stem Cells Suggests Paths to Initiation and Progression of a Precancerous Lesion. Nat. Commun., 7: 10380. (2016) PMID: 26783136
  3. Yamamoto Y, Ning G, Howitt BE, Mehra K, Wu L, Wang X, Hong Y, Kern F, Tay SW, Zhang T, Nagarajan N, Basuli D, Torti S, Brewer M, Choolani M, McKeon F, Crum CP & Xian W. In Vitro and In Vivo Correlates of Physiologic and Neoplastic Human Fallopian Tube Stem Cells. J Pathol., 238(4): 519-530. (2016) PMID: 26415052
  4. Wang X*, Yamamoto Y* (co-first author), Wilson LH, Zhang T, Howitt B, Farrow MA, Kern F, Ning G, Hong Y, Khor CC, Chevalier B, Bertrand D, Nagarajan N, Sylvester FA, Hyams JS, Devers T, Bronson R, Lacy DB, Ho KY, Crum CP, McKeon F, & Xian W. Cloning and Variation of Ground State Intestinal Stem Cells. Nature, 522 (7555): 173-178. (2015) (Research Highlight in Cell Research and Preview in Cell Stem Cell) PMID: 26040716
  5. Zuo W, Wu DZ, Zhang T, Guan SP, Liew A, Yamamoto Y, Vincent M, Lessard M, Crum CP, Wang X, Lim SJ, Xian W & McKeon F. p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration, Nature, 517 (7536): 616-620. (2015) (Highlighted in NEWS & VIEWS, Nature) PMID: 25383540
  6. Ning G, Bijron JG, Yamamoto Y, Wang X, Howitt BE, Herfs M, Yang E, Hong Y, Cornille M, Wu L, Hanamornroongruang S, McKeon FD, Crum CP & Xian W. PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium. J Pathol., 234(4): 478-487. (2014) PMID: 25130537
  7. Herfs M, Vargas SO, Yamamoto Y, Howitt B, Nucci MR, McKeon FD, Xian W & Crum CP. A novel blueprint for “top down” differentiation defines the cervical squamo-columnar junction during development, reproductive life and neoplasia. J Pathol., 229(3): 460-468. (2013) PMID: 23007879
  8. Herfs M, Yamamoto Y, Laury A, Wang X, Nucci MR, McLaughlin-Druben M, Munger K, Feldman S, McKeon FD, Xian W & Crum CP. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci U S A., 109(26), 10516-10521. (2012) (selected in Faculty of 1000, Infectious Diseases) PMID: 22689991
  9. Kumar PA*, Hu Y*, Yamamoto Y, Neo BH, Tay SW, Mu D, Sun Y, Lim SJ, Daghers R, Zielonka E, Wang DY, Chow VT, Crum CP, Xian W & McKeon F. Distal Airway Stem Cells Render Alveoli in Vitro and During Lung Regeneration Following H1N1 Influenza Infection. Cell, 147, 525-538. (2011)*These authors are equally contributed in this work.(Highlighted in Science (Editor’s Choice) and Nature) PMID: 22036562
  10. Wang X*, Ouyang H*, Yamamoto Y* (co-first author), Kumar PA, Tay SW, Dagner R, Vincent M, Lu, X, Bellizzi, AM Ho KY, Crum CP, Xian W & McKeon F. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell, 145, 1023-1035. (2011) (Featured Article in Cell. Highlighted in Nature Reviews Cancer. Faculty of 1000 Biology: 10 (Exceptional) PMID: 21703447