Human organic anion transporters (hOATs) play critical roles in the body disposition of clinically important drugs. Understanding the regulation of hOATs has profound clinical significance. My thesis work focuses on delineating molecular and cellular mechanisms underlying hOAT regulation, and consists of three parts. In the first part, we examined the regulation of hOAT trafficking and function by ubiquitination through cell signaling pathways (protein kinase C, protein kinase A, and their upstream hormones AngII and bradykinin) by combined approaches of cellular biology, site-directed mutagenesis and mass spectroscopy. We identified PKC isoforms involved in OAT regulation. We also identified lysine residues serving as ubiquitin-conjugating sites. In the second part, we examined transporter-mediated drug-drug interactions by screening two prescription drug libraries against hOAT1 and hOAT3. High potent inhibitors were identified. Computational analyses reveal several important properties which differentiate between inhibitors and non-inhibitors. Such model provides mechanistic insights for predicting new OAT inhibitors. In the third part, we studied structure and function relationship of hOATs. Critical transmembrane domain and amino acid residues were identified, which play important role in OAT stability, maturation efficiency as well as ologomerization.
Subject (authority = RUETD)
Topic
Pharmaceutical Science
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_4933
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
vii, 103 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Shanshan Li
Subject (authority = ETD-LCSH)
Topic
Anions
Subject (authority = ETD-LCSH)
Topic
Human physiology
Subject (authority = ETD-LCSH)
Topic
Cytology--Research
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
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.