Anushka Choudhary - Undergraduate Researcher (Vandy Class of 2019)
The effects of dietary and environmental chemicals on liver cancer gene expression.
Hometown - Houston,TX
Major in Neuroscience
Major in Child Development
Pre-Medical Student, Vanderbilt University College of Arts & Sciences
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.