Previous research from our lab has shown that phosphoinositide phospholipids (PIPs) are important in the regulation of the  transcriptional activity of SF-1. Inhibition of IPMK using aurintricarboxylic acid (ATA) has shown to decrease transcriptional activity of SF-1. ATA is a known inhibitor of IPMK. The mechanism of liver homolog receptor 1 (LRH-1) activation is currently uncharacterized; but, due to high sequence homology and three-dimensional structural homology with SF-1, coupled with the fact that both LRH-1 and SF-1 bind PIP2 and PIP3 with high affinity, my hypothesis is that:

SF-1 and the close homolog LRH-1 have a similar mode of activation by IPMK. We will determine the effect of the IPMK inhibitor (ATA) on LRH-1 dependent transcription.

 

We expect to see the expression of LRH-1 target genes decrease upon ATA treatment: this would suggest that IPMK activates LRH-1 in the same way as it does SF-1. This discovery would be important to biomedical science because abnormal hormone signaling is a strong driver of cancer development; thus, drugs targeting IPMK could be used to inhibit tumors. In addition to understanding the activity of LRH-1 as compared with SF-1, another goal is to identify any effect that commonly used compounds such as Bisphenol A and atrazine would have on the cell proliferation and target gene expression of LRH-1 in HepG2 cells. Dilauryl PC (DLPC), another phospholipid that can bind to LRH-1 will also be tested in its effects on LRH-1 target genes as its effect has been studied in other cell types, now to be tested in the HepG2 cell line.

Urvashi Mathur - Undergraduate Researcher (Vandy Class of 2018)

The effects of dietary and environmental chemicals on liver cancer gene expression.                                                                                      

Hometown -  Houston, TX

Major in Neuroscience

Major in Medicine Health and Society

Minor in Spanish

Pre-Medical Student, Vanderbilt University College of Arts & Sciences

 

 

The Journal of Biological Chemistry Herb Tabor Award to Ray Blind Vanderbilt University.
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National Cancer Institute Transition to Indepedence Award to Ray Blind Vanderbilt University
National Institute of General Medical Sciences Institutional Research and Career Development Fellowship to Ray Blind, Vanderbilt University
Vanderbilt Diabetes Research and Training Center
Vanderbilt Ingram Cancer Center
Vanderbilt Institute of Chemical Biology
Vanderbilt Center for Structural Biology
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