dc.creator | Lin, Luping | |
dc.date.accessioned | 2020-08-23T15:42:10Z | |
dc.date.available | 2012-11-08 | |
dc.date.issued | 2011-11-08 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-11012011-164959 | |
dc.identifier.uri | http://hdl.handle.net/1803/14409 | |
dc.description.abstract | Dysregulation 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.format.mimetype | application/pdf | |
dc.subject | lung cancer | |
dc.subject | Notch3 | |
dc.subject | Jagged1 | |
dc.subject | CSL | |
dc.subject | therapeutic agents | |
dc.subject | cancer biology | |
dc.title | Targeting Notch3 signaling in lung cancer | |
dc.type | dissertation | |
dc.contributor.committeeMember | Harold Moses | |
dc.contributor.committeeMember | Martin Egli | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cancer Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2012-11-08 | |
local.embargo.lift | 2012-11-08 | |
dc.contributor.committeeChair | Barbara Fingleton | |
dc.contributor.committeeChair | David Carbone | |