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Structure-function relationship and regulation of organic anion transporters (OATS)

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Title
Structure-function relationship and regulation of organic anion transporters (OATS)
Name (ID = NAME001); (type = personal)
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Zhou
NamePart (type = given)
Fanfan
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Fanfan Zhou
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author
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You
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Guofeng
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Advisory Committee
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Guofeng You
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chair
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Minko
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Tamara
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Advisory Committee
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Tamara Minko
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internal member
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Michniak
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Bo
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Advisory Committee
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Bo Michniak
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internal member
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NamePart (type = family)
Pan
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Zui
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Advisory Committee
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Zui Pan
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outside member
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Rutgers University
Role
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degree grantor
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Graduate School - New Brunswick
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school
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Text
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theses
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DateCreated (qualifier = exact)
2008
DateOther (qualifier = exact); (type = degree)
2008-01
Language
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English
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electronic
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application/pdf
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v, 259 pages
Abstract
The organic anion transporter (OAT) family has been identified to express in multiple human organs, such as kidney, liver, brain and placenta. They mediate the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs and therefore are critical for the survival of mammalian species. My research work has focused on the elucidation of the structure-function relationship and regulation of OATs.
It was known that glycosylation of proteins play critical roles in many cell functions. My studies have identified that the addition/acquisition of oligosaccharides but not the processing of the added oligosaccharides plays a critical role in the targeting of hOAT4 to the plasma membrane. Processing of added oligosaccharides from mannose-rich type to complex type is important for enhancing the binding affinity of hOAT4 for its substrates.
According to the alignment of several OATs isolated from different species, my studies have explored several conserved important residues on human organic anion transporter 4 (hOAT4), which affect transporter function by impairing the trafficking of the transporter to the cell surface or its binding ability for the substrates.
I have also characterized the organic anion transport system in rat and human placental cell lines, Hrp1 and Bewo, which has great significance in establishing the useful in vitro models for the studies of the transfer of nutrients and drugs between mother and the fetus and providing important information for the understanding of placental physiology and diseases.
Furthermore, my studies have explored that organic anion transporter function can be regulated by protein kinase C and placental hormones. I have investigated the differences between the interaction of PDZ proteins with hOAT4 in kidney cells and that in placental cells as well. My data indicated that the interacting partners of hOAT4 in placenta may be different from that in kidney.
The information obtained from my studies will be great significance to the development of clinically useful drugs and to the advancement of our understanding of the molecular, cellular, and clinical bases of renal, hepatic, neurological and fetal toxicity and diseases.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references.
Subject (ID = SUBJ1); (authority = RUETD)
Topic
Pharmaceutical Science
Subject (ID = SUBJ2); (authority = ETD-LCSH)
Topic
Drugs--Physiological transport
Subject (ID = SUBJ3); (authority = ETD-LCSH)
Topic
Drug carriers (Pharmacy)
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17246
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ETD_623
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T33B60HG
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
Copyright
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Copyright protected
Availability
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Open
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Name
Fanfan Zhou
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Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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Author Agreement License
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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.
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