Xiang-Xi (Mike) Xu, Ph.D.

Professor of Medicine

Description of Research

Dr. Xu is interested in ovarian cancer biology and the mechanism of early embryogenesis. Dr. Xu’s laboratory research explores the molecular mechanisms of epithelial morphogenesis during embryogenesis and the alterations that lead to epithelial cell transformation in carcinogenesis. One hallmark of carcinomas, malignancies of epithelial origin, is the loss of cell positional organization: cancer cells are no longer arranged as a discrete epithelium. Thus, genes and mechanisms governing epithelial cell organization are obviously necessary targets of carcinogenic alterations. Often these genes and mechanisms are also involved in epithelial morphogenesis during embryonic development. Dr. Xu’s laboratory concentrates on two epithelial biological systems: transformation of the genesis of the primitive ovarian surface epithelium to cancer, and endoderm, an epithelial structure in early embryos. They have recognized a striking conservation in the molecular mechanisms and genes between epithelial morphogenesis and neoplastic transformation, and are studied in parallel both development and cancer.

Additonally, Dr. Xu's laboratory is interested in the study of the role of genetic instability in cancer development. The studies concern the link between nuclear envelope defects and chromosomal numerical instability, as well as the potential role of the disregulation of endogenous transposons and retrovirus elements in altering the genomic landscape of cancer cells.

Lastly, Dr. Xu's laboratory participates in a collaborative project to investigate the application of oncolytic therapy to treat drug-resistant ovarian cancer. Dr. Xu hopes that the studies will reveal critical mechanisms in ovarian carcinogenesis and also contribute to the fundamental understanding of cell differentiation and morphogenesis in early embryonic development.

Highlights

Discovery and establishment of Dab2 as a tumor suppressor
Uncovered the role of Dab2 gene in epithelial polarity and in morphological transformation of carcinoma cells
Finding of the role of GATA transcription factors in epithelial dedifferentiation of ovarian cancer cells
Development of an ovarian tumor mouse model reflecting postmenopausal ovarian cancer risk
Discovery of nuclear envelope defects as the causes of chromosomal instability in ovarian cancer
Discovery of mechanisms in cell differentiation and pattern formation in early embryogenesis

Selected Cancer-Related Publications

Capo-Chichi CD, Cai KQ, Smedberg J, Ganjei-Azar P, Godwin AK, Xu XX. Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer. Chin J Cancer 30:415-25, 2011. Read more »
Smith ER, Zhang XY, Capo-Chichi CD, Chen X, Xu XX. Increased expression of Syne1/nesprin-1 facilitates nuclear envelope structure changes in embryonic stem cell differentiation. Dev Dyn 240:2245-55, 2011. Read more »
Heiber JF, Xu XX, Barber GN. Potential of vesicular stomatitis virus as an oncolytic therapy for recurrent and drug-resistant ovarian cancer. Chin J Cancer 30:805-14, 2011. Read more »
Capo-Chichi CD, Cai KQ, Simpkins F, Ganjei-Azar P, Godwin AK, Xu XX. Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer. BMC Med 9:28, 2011. Read more »
Wang Y, Smedberg JL, Cai KQ, Capo-Chichi DC, Xu XX. Ectopic expression of GATA6 bypasses requirement for Grb2 in primitive endoderm formation. Dev Dyn 240:566-76, 2011. Read more »
Capo-Chichi CD, Yeasky TM, Heiber JF, Wang Y, Barber GN, Xu XX. Explicit targeting of transformed cells by VSV in ovarian epithelial tumor-bearing Wv mouse models. Gynecol Oncol 116:269-275, 2010. Read more »
Smith ER, Xu XX. REDD1, a new Ras oncogenic effector. Cell Cycle 8:675-6, 2009. Read more »
Yang DH, Smith ER, Cai KQ, Xu XX. c-fos elimination compensates for disabled-2 requirement in mouse extraembryonic endoderm development. Dev Dyn 238:514-523, 2009. Read more »

Programs

Collaborating in the Multidisciplinary Research Program(s):