Faculty : Departmental- Primary

Elizabeth R. Smith, Ph.D.

Controlling cell growth and proliferation is critical to the maintenance of differentiated tissues, and loss of this regulation is a hallmark of transformation and malignancy. The Ras/MAPK signaling cascade is used by many growth factors and mitogens to induce cell proliferation, and it is found frequently deregulated in cancers and tumor development. Moreover, MAPK signaling is essential for the formation of the embryonic endoderm lineage derived from ES cells. Our work focuses on the mechanisms responsible for MAPK nucleocytoplasmic regulation, and we have considered that transformation of an epithelium is a de-differentiation event and use as models the differentiation of embryonic stem cells to epithelial-like cells, as well as primary mouse and human ovarian and fallopian epithelial cells compared to ovarian cancer cell lines and tissues. Studies are currently investigating Nesprins and other nuclear envelope structural proteins in regulation of MAPK nuclear entry in differentiated cells and in development of ovarian cancer stem cell phenotypes. We are also interested in the development and study of an ovarian tumor mouse model that reflects menopausal ovarian cancer risk.

Professional Affiliations

University of Miami Sylvester Comprehensive Cancer Center

Select Publications

  • Smith ER, Yeasky T, Wei JQ, Miki RA, Cai KQ, Smedberg JL, Yang WL, Xu XX. White spotting variant (Wv) mouse as an experimental model for ovarian aging and menopausal biology. Menopause 19(5), 2012 (in press).
  • Smith ER, Zhang XY, Capo-chichi CD, Chen X, Xu XX. Increased expression of Syne-1/Nesprin-1 facilitates nuclear envelope structure changes in embryonic stem cell differentiation. Dev Dyn 240(1):2245-55, 2011.
  • Smith ER, Cai KQ, Smedberg JL, Ribeiro MM, Rula ME, Slater C, Godwin AK, and Xu XX. Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells. PLoS ONE 5(2):e9295, 2010.
  • Cai KQ, Caslini C, Capo-chichi CD, Slater C, Smith ER, Wu H, Klein-Szanto AJ, Godwin AK, and Xu XX. Loss of GATA4 and GATA6 expression specifies ovarian cancer histological subtypes and precedes neoplastic transformation of ovarian surface epithelia. PLoS ONE 4(7):e6454, 2009.
  • Smith ER, and Xu XX. News & Views: REDD1, a new Ras oncogenic effector. Cell Cycle 8(5): 675-6, 2009.
  • Yang DH, Smith E, Cai K, and Xu XX. c-Fos elimination compensates for disabled-2 requirement in mouse extraembryonic development. Develop Dyn 238(3):514-523, 2009.
  • Smith ER, and Xu XX. Ovarian aging, follicle depletion, and cancer: a hypothesis for the etiology of epithelial ovarian cancer involving follicle depletion. Lancet Oncol. 9(11):1108-1111, 2008.
  • Yang DH, Cai KQ, Roland IH, Smith ER, and Xu XX. Disabled-2 is an epithelial surface positioning gene. J Biol Chem. 282(17):13114-13122, 2007.
  • Yang WL, Cai KQ, Smedberg JL, Smith ER, Klein-Szanto A, Hamilton TC, and Xu XX. A reduction of cyclooxygenase-2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice. Am J Pathol. 170(4):1325-1336, 2007.
  • Rula ME, Cai KQ, Moore R, Yang DH, Staub CM, Capo-Chichi CD, Jablonski SA, Howe PH, Smith ER, Xu XX. Cell autonomous sorting and surface positioning in the formation of primitive endoderm in embryoid bodies. Genesis 45(6):327-328, 2007.
  • Yang DH, Fazilli Z, Smith ER, Cai KQ, Klein-Szanto A, Cohen C, Horowitz IR, and Xu XX. Disabled-2 heterozygous mice are predisposed to endometrial and ovarian tumorigenesis and exhibit sex-biased embryonic lethality in a p53-null background. Am J Pathol. 169(1):258-267, 2006.
  • Smith ER, Daly MB, and Xu XX. A mechanism for COX-2 inhibitor anti-inflammatory activity in chemoprevention of epithelial cancers. Cancer Epidem Biomark Prevent. 13:(1)144-145, 2004.
  • Smith ER, Smedberg JL, Rula ME, and Xu XX. Regulation of Ras/MAPK mitogenic activity by restricting nuclear entry in endoderm differentiation of embryonic carcinoma and stem cells. J Cell Biol. 164(5):689-699, 2004.

View published research articles by Dr. E.R.Smith in the National Library of Medicine.