Notch signaling defines an evolutionarily conserved cell interaction mechanism that broadly controls cell fate acquisition in metazoans and consequently, profoundly affects cellular differentiation, apoptosis and proliferation. In humans, Notch signaling abnormalities have been linked to a variety of pathogenic conditions and its involvement in carcinogenesis is being increasingly appreciated, thus Notch has become an important potential target for cancer therapy. We propose to explore specific models and unique transgenic reagents we developed which now allow us to address systematically the fundamental question of Notch signal integration at the cellular level, and in particular, how it relates to the synergy of Notch signals with other cellular elements to influence, cause or sustain oncogenesis in the mammary epithelium.

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Our work directly addresses the link between Notch signaling and tumorigenesis in the mammary gland. We are taking advantage of novel transgenic mice we generated to study the effects of Notch signals in the mammary epithelium, while we also use Drosophila Genetics as a powerful tool to examine how Notch signals integrate their action with other cellular elements to affect cell proliferation. Our goal is to gain insights into the involvement of Notch signaling in cell proliferation and consequently its involvement in breast cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Cancer Molecular Pathobiology Study Section (CAMP)
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Yassin, Rihab R,
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Harvard University
Anatomy/Cell Biology
Schools of Medicine
United States
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Ho, Diana M; Pallavi, S K; Artavanis-Tsakonas, Spyros (2015) The Notch-mediated hyperplasia circuitry in Drosophila reveals a Src-JNK signaling axis. Elife 4:e05996
Hori, Kazuya; Sen, Anindya; Artavanis-Tsakonas, Spyros (2014) Genetic circuitry modulating notch signals through endosomal trafficking. Methods Enzymol 534:283-99
Fleming, Robert J; Hori, Kazuya; Sen, Anindya et al. (2013) An extracellular region of Serrate is essential for ligand-induced cis-inhibition of Notch signaling. Development 140:2039-49
Oh, Philmo; Lobry, Camille; Gao, Jie et al. (2013) In vivo mapping of notch pathway activity in normal and stress hematopoiesis. Cell Stem Cell 13:190-204
Hori, Kazuya; Sen, Anindya; Artavanis-Tsakonas, Spyros (2013) Notch signaling at a glance. J Cell Sci 126:2135-40
ล ale, Sanja; Lafkas, Daniel; Artavanis-Tsakonas, Spyros (2013) Notch2 genetic fate mapping reveals two previously unrecognized mammary epithelial lineages. Nat Cell Biol 15:451-60
Hori, Kazuya; Sen, Anindya; Kirchhausen, Tom et al. (2012) Regulation of ligand-independent Notch signal through intracellular trafficking. Commun Integr Biol 5:374-6
Guruharsha, K G; Kankel, Mark W; Artavanis-Tsakonas, Spyros (2012) The Notch signalling system: recent insights into the complexity of a conserved pathway. Nat Rev Genet 13:654-66
Louvi, Angeliki; Artavanis-Tsakonas, Spyros (2012) Notch and disease: a growing field. Semin Cell Dev Biol 23:473-80
Pallavi, S K; Ho, Diana M; Hicks, Chindo et al. (2012) Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in Drosophila. EMBO J 31:2895-907

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