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Analysis of the cell-adhesion signaling network and its crosstalk with the epidermal growth factor pathway in primary rat hepatocytes
Descriptive
TitleInfo
Title
Analysis of the cell-adhesion signaling network and its crosstalk with the epidermal growth factor pathway in primary rat hepatocytes
Name
(type = personal)
NamePart
(type = family)
Andrianarijaona
NamePart
(type = given)
Tsirisoa
NamePart
(type = date)
1972-
DisplayForm
Tsirisoa Andrianarijaona
Role
RoleTerm
(authority = RULIB)
author
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(type = personal)
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(type = family)
Roth
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(type = given)
Charles M
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Charles M Roth
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Advisory Committee
Role
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(authority = RULIB)
chair
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(type = personal)
NamePart
(type = family)
Moghe
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(type = given)
Prabhas
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Prabhas Moghe
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Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Shinbrot
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(type = given)
Troy
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Troy Shinbrot
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Nanda
NamePart
(type = given)
Vikas
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Vikas Nanda
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Yakoby
NamePart
(type = given)
Nir
DisplayForm
Nir Yakoby
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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school
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Text
Genre
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theses
OriginInfo
DateCreated
(qualifier = exact)
2013
DateOther
(qualifier = exact);
(type = degree)
2013-10
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
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(type = code)
eng
Abstract
(type = abstract)
Cultured primary hepatocytes provide excellent platforms for the experimental study of the toxicology and the metabolism of various potentially harmful compounds. However, the usefulness of primary hepatocytes is significantly hampered by their loss of specific functions in vitro through a process called dedifferentiation. In general, dedifferentiation results from the loss of the normal balance of proliferation and differentiation, which are mutually exclusive in vitro. Therefore, a clear understanding of the mechanisms that drive hepatocyte proliferation in culture would certainly provide valuable information for the design of new cell culture systems. This doctoral dissertation is focused on understanding the dynamical properties of the rat hepatocyte-adhesion signaling network and its crosstalk with the MAPK/ERK pathway. A major part of this thesis was focused on designing a mathematical model of the coupled integrin and E-cadherin/-catenin signaling pathways to analyze the property of their underlying control system. Combining bifurcation analysis with single-cell measurements, this study provided the evidence that the hepatocyte adhesion pathways exhibit a bistability in response to changes in PIP2 cellular levels, and thereby may undergo a switch between a strong integrin-based/weak E-cadherin-based adhesion, and a weak integrin-based/strong E-cadherin-based adhesion. Rat hepatocytes secrete fibronectin in culture, and this study showed that the strong integrin-based adhesion resulted from a fibronectin-mediated activation of the integrin pathway. A strong integrin-based adhesion primes the hepatocytes for a maximal responsiveness to EGF, which was characterized by a sustained activation of the MAPK/ERK pathway in mid G1 and the ensuing full cell commitment to proliferation. The adhesion-dependent priming was characterized by an upregulation of certain MAPK/ERK activators. The overall results from this dissertation provide a better insight into the design of novel hepatocyte culture systems that will be more conducive to the preservation of hepatocyte differentiation. Additionally, the mathematical model that was designed in this study provides a foundation for future in-depth studies of the cell-adhesion network in various cell types.
Subject
(authority = RUETD)
Topic
Biochemistry
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
Identifier
ETD_5144
PhysicalDescription
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electronic resource
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application/pdf
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text/xml
Extent
xii, 127 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Tsirisoa Solon'i Aina Andrianarijaona
Subject
(authority = ETD-LCSH)
Topic
Liver cells--Differentiation
Subject
(authority = ETD-LCSH)
Topic
Rats--Physiology
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3BR8Q66
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Andrianarijaona
GivenName
Tsirisoa
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(point = start)
2013-10-03 15:35:38
AssociatedEntity
Name
Tsirisoa Andrianarijaona
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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
DateTime
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2013-10-31
DateTime
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2015-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2015.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ContentModel
ETD
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windows xp
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