Broadly, our lab studies nuclear lipid signaling. We are specifically interested in the mechanisms by which phospholipids regulate gene expression. Blind et. al. (2012) showed that a key signaling phosphoinositide, PIP2, is able to bind steroidogenic factor 1 (SF-1), a NR, and antagonize its transcriptional activity. However, PIP3 bound to SF-1 activates transcription of SF-1 target genes. The conversion of PIP2 to PIP3 is mediated by a lipid kinase, IPMK, while the lipid is bound to the receptor, suggesting that IPMK is a critical regulator of SF-1 activity when the receptor is bound by PIP2. SF-1 has a close homolog, LRH-1 (liver receptor homolog), that shares many of the same target genes. We hypothesize that the activity of LRH-1 bound to PIP2 can also be regulated by IPMK.
PI: Raymond Blind, Ph.D.