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Generation of anti-tumorigenic MET receptor variants by splicing interference
Descriptive
TitleInfo
Title
Generation of anti-tumorigenic MET receptor variants by splicing interference
Name
(type = personal)
NamePart
(type = family)
Rathod
NamePart
(type = given)
Trushar
NamePart
(type = date)
1979-
DisplayForm
Trushar Rathod
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Suh
NamePart
(type = given)
Nanjoo
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Nanjoo Suh
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Cartegni
NamePart
(type = given)
Luca
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Luca Cartegni
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Zhou
NamePart
(type = given)
Renping
DisplayForm
Renping Zhou
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Scaltriti
NamePart
(type = given)
Maurizio
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Maurizio Scaltriti
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
School of Graduate Studies
Role
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school
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Text
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theses
OriginInfo
DateCreated
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2019
DateOther
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(qualifier = exact);
(type = degree)
2019-05
CopyrightDate
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(qualifier = exact)
2019
Language
LanguageTerm
(authority = ISO 639-3:2007);
(type = text)
English
Abstract
(type = abstract)
Aberrant activation of MET, a receptor tyrosine kinase (RTK), leads to tumor growth, invasion and metastasis and is implicated in multiple types of cancers. Hence, various strategies have been employed to target MET for cancer therapy including recombinant form of MET ectodomain to sequester ligand and suppress MET activity. Here, we describe multiple C-terminal truncated MET decoys receptors (sdMET) with therapeutic potential. We show that these sdMET isoforms are translated from stable mRNA variants which are generated via Intronic polyadenylation (IPA) of MET’s pre-mRNA in a U1-snRNP (U1) dependent manner. Moreover, we demonstrate increase in sdMET IPA isoforms of choice at expense of full-length MET with our antisense-based strategy by blocking U1 binding to specific 5’ splice site and activating downstream intronic poly (A) site. Our strategy is an improvement of current methods due to its two-pronged approach: suppress MET activity in targeted cells by converting oncogenic MET into soluble decoy to have dominant negative effect on surround microenvironment in paracrine manner.
Subject
(authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
Subject
(authority = LCSH)
Topic
Hepatocyte growth factor -- Receptors
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_9708
PhysicalDescription
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application/pdf
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text/xml
Extent
1 online resource (xviii, 154 pages) : illustrations
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
RelatedItem
(type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier
(type = local)
rucore10001600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/t3-jzv7-qa62
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Rathod
GivenName
Trushar
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2019-04-07 18:22:57
AssociatedEntity
Name
Trushar Rathod
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
Type
Embargo
DateTime
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(qualifier = exact);
(point = start)
2019-05-31
DateTime
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(point = end)
2020-05-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 30th, 2020.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ETD
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windows xp
DateCreated
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2019-06-17T12:51:13
CreatingApplication
Version
1.7
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