Uniform TitleStructure-function relationship and regulation of organic anion transporters (OATS)
NameZhou, Fanfan (author), You, Guofeng (chair), Minko, Tamara (internal member), Michniak, Bo (internal member), Pan, Zui (outside member), Rutgers University, Graduate School - New Brunswick,
Drug carriers (Pharmacy)
DescriptionThe 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.
NoteIncludes bibliographical references.
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.