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Mentor: Michael Duffel, PhD
Year Entered Into Program: 2012-2014
PhD Institution: University of Iowa, 2014 (MS)
My current research deals with polychlorinated biphenyl (PCB) sulfates and their affinity to thyroxine-binding globulin (TBG). PCBs were used in many applications until the late 1970’s, when their production was banned worldwide. PCBs are linked to numerous health issues ranging from cognitive and behavioral issues, to hypothyroidism, and even cancer. Although banning PCB production was seen as a necessity, the removal of many products already made with them was not. There are even public schools and other older buildings that are still in use to this day where PCBs are being released from lighting fixtures and building materials. Not too long ago it was also discovered that, despite the banning of PCB production, PCBs were being found in air samples collected in both indoor and outdoor air, and new PCBs were found to be a byproduct in current manufacture of certain paint pigments. Much research has been done on PCBs, and hydroxylated metabolites of PCBs. Much less is known about sulfate metabolites of PCBs. These sulfates were previously thought to just be simply excreted, but this may not be the case. Recent studies indicate that PCB sulfates mimic thyroxine (T4) in binding to transthyretin. My current research is based on the hypothesis that PCB sulfates bind thyroid binding globulin (TBG) and may therefore disrupt its function as the major carrier of T4 in humans. I’ve been developing an assay using a fluorescent probe that will bind the active site of TBG so that I can titrate competing ligands (i.e., PCB sulfates) and determine their binding affinities for TBG. With this data I will develop quantitative structure-activity (QSAR) models to give us a better means to predict the structures of those PCB sulfates (and perhaps other organic sulfates) that can bind to TBG. This overall approach is not only important for PCB metabolites, but for other xenobiotics where hydrophobic aromatic sulfate esters are metabolites. Such interactions with carrier proteins and receptors may constitute important new biological activities for hydrophobic sulfate esters as metabolic products of xenobiotics that range from drugs to environmental toxins.
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