Assistant Professor, Department of Neurobiology & Anatomical SciencesTumor Cell Biology ProgramPhD, Biochemistry, 2001, Rutgers UniversityPostdoc, 2001-06, The Hospital for Sick Children, Toronto, Canada
Contact information2500 N State St., Room G757Jackson, MS 39216E-mail: email@example.com
Fringe-modulated Notch signaling in the development and cancer of mammary gland, prostate and lung
Cancer stem cells
Breast cancers are heterogeneous at clinical and molecular level. Different subtypes of breast cancer may have different cell-of-origin within mammary epithelial hierarchy. Notch signaling controls mammary epithelial cell fate decision and differentiation. Thus genetic dissection of Notch pathways in the mammary gland may provide insights into intrinsic subtypes of breast cancer. We showed that Lunatic Fringe (Lfng), a glycosyltransferase that modifies Notch receptors thereby modulating Notch activation, regulates mammary stem/progenitor cell activity, and Lfng deficiency cooperates with the Met/Caveolin amplicon to induce basal-like breast cancer. Most recently we defined an oncogenic role for Manic Fringe (Mfng) through Notch-mediated Pik3cg induction in claudin-low breast cancer.
Elevated Notch ligand and receptor expression has been associated with aggressive forms of prostate cancer, suggesting a role for Notch signaling in prostate tumor initiation and progression. We have reported a critical role for Lfng in regulation of prostate epithelial differentiation and proliferation, as well as in prostate tumor suppression, through differential modulation of Notch receptor activation. We are currently determining roles of Lfng in the pathogenesis of basal- and luminal-originated prostate cancers.
Notch signaling coordinates a series of events during lung development, including proximodistal fate generation and branching, proximal airway cell fate specification, and alveologenesis. We have found that Jagged1 is the major regulator of Notch-dependent cell fate in proximal airways, and that Lfng-dependent Notch signaling is required for alveologenesis. Notch also plays complex roles in lung carcinogenesis, with the cellular (SCLC vs NSCLC) and microenvironmental (hypoxia) context profoundly affecting tumor cell response to Notch activation. We are interested in identifying Notch pathway genes as biomarker and therapeutic targets for lung cancer.
2500 North State Street
Jackson, MS 39216
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