Keli Xu
Assistant Professor, Department of Neurobiology & Anatomical Sciences
Tumor Cell Biology Program
Ph.D., Biochemistry, 2001, Rutgers University
Postdoc, 2001-2006, The Hospital for Sick Children, Toronto
Contact Information
2500 N State St, Room G757
Jackson, MS 39216
Email: kxu@umc.edu
Research Interests
- Notch signaling pathway in mammary development and breast cancer
- Notch activation in lung development and lung cancer
- Fringe proteins
Research Synopsis
The Notch system is a powerful regulator in development and homeostasis of multiple tissues. Dysregulation of Notch signaling has been implicated in various pathological conditions including cancer. We are interested in understanding roles of Notch signaling in the development of mammary gland, and lung, as well as its involvement in breast cancer and lung cancer. Lunatic Fringe (Lfng), a glycosyltransferase that modifies Notch receptor and modulates Notch activation, is expressed in stem/progenitor cells in many tissues including breast and lung. Fine-tuning of Notch signaling by Fringe may be critical in regulation of stem cell function.
Cancers are heterogeneous at clinical and molecular level. Human breast cancers have been classified into five molecular subtypes: luminal, HER2-enriched, basal-like, caludin-low and normal breast-like. There is emerging evidence that different tumor subtypes originated from distinct cell types within mammary epithelial hierarchy. Understanding the cell of origin of each type will facilitate identifying specific therapeutic targets. Notch signaling regulates mammary epithelial cell specification, proliferation and differentiation. Genetic dissection of Notch pathway in normal and oncogenic mammary development will provide insights on intrinsic subtypes of breast cancer.
Notch signaling coordinates events during lung development, including early proximodistal fate generation and branching, airway epithelial cell fate specification, alveogenesis and pulmonary vascular development. In addition, Notch plays complex roles in lung carcinogenesis, with the cellular (SCLC vs NSCLC) and microenvironmental (hypoxia) context profoundly effecting tumor cell response to Notch activation. Individual Notch receptors, ligands or the Fringe proteins are candidates for lung cancer biomarker and therapeutic targeting.
Recent Accomplishments and Honors
2003-2006 Canadian Institutes of Health Research (CIHR) Fellowship
Selected Publications
- Adams JR et al. Cooperation between PIK3Cα and p53 mutations in mouse mammary tumor formation. Cancer Research 71(7), 2706-2717, 2011.
- Yuan JS et al. Lunatic Fringe prolongs Delta/Notch-induced self-renewal of committed αβ T-cell progenitors. Blood 117(4), 1184-1195, 2011.
- Xu K et al. Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol 298, L45-56, 2010.
- Tan JB et al. Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches. Immunity 30, 254-263, 2009.
- Xu K et al. Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca2+ release from the endoplasmic reticulum. Neuron 31, 957-971, 2001.
