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Targeting Notch3 signaling in lung cancer

dc.creatorLin, Luping
dc.description.abstractDysregulation of the Notch signaling pathway plays an important role in lung cancer pathobiology. The Notch3 receptor is overexpressed in ∼40% of resected non-small cell lung cancers, and its suppression results in loss of the malignant phenotype both in vitro and in vivo. In this dissertation, I have identified novel ligand binding regions in the Notch3 receptor using a high throughput system and a Notch3 peptide library that spans the extrcellular domain. This knowledge allowed me to generated Fc-fusion proteins and neutralizing monoclonal antibodies to target these regions in the Notch3 receptor thereby interfering with signaling by blocking the interaction of the receptor with it’s ligands. In addition, I explored the roles of Jagged1, a Notch ligand, in lung cancer. I demonstrate that Jagged1 has the paradoxical roles of increasing cell growth and suppressing migration. Interestingly, this appears to be through a noncanonical, CSL-independent mechanism. The findings of these studies not only give novel insights into Notch3 signaling but also establish a foundation on which targeted therapies can be developed.
dc.subjectlung cancer
dc.subjecttherapeutic agents
dc.subjectcancer biology
dc.titleTargeting Notch3 signaling in lung cancer
dc.contributor.committeeMemberHarold Moses
dc.contributor.committeeMemberMartin Egli
dc.type.materialtext Biology University
dc.contributor.committeeChairBarbara Fingleton
dc.contributor.committeeChairDavid Carbone

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