2026-2027 Faculty Research Grants

Marlene Murray (Biology). 

Stress Hormone Modulation of Inositol Biosynthesis in Bipolar Disorder Subtypes.

Bipolar disorder (BD) is a severe mood disorder affecting 1–2% of the global population and remains difficult to diagnose and treat due to clinical heterogeneity and the absence of validated biochemical biomarkers. Bipolar I (BDI) and Bipolar II (BDII) differ in symptom presentation and treatment response, suggesting distinct underlying molecular mechanisms. Evidence implicates dysregulation of the inositol biosynthetic–phosphoinositide signaling network in BD. Myo-inositol is a critical precursor for phosphoinositide signaling, which regulates G-protein–coupled receptor activity, second messenger generation, and downstream kinase activation. Altered brain inositol levels have been observed during both manic and depressive episodes, and first-line mood stabilizers are thought to exert therapeutic effects through modulation of inositol metabolism. Stress biology also plays a central role in BD. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol levels are documented in both manic and depressive states. Preliminary findings from my lab demonstrate that cortisol differentially modulates RasGRP1, a signaling protein linking phosphoinositide metabolism and inflammatory pathways, in BD subtypes. This study will investigate whether cortisol differentially alters intracellular myo-inositol levels and expression of key inositol biosynthetic genes (INO1, ISYNA1) at both transcriptional (RT-qPCR) and translational (immunoblot) levels in lymphoblastoid cell lines derived from BDI, BDII, and neurotypical individuals. I hypothesize that cortisol induces subtype-specific molecular responses within the inositol signaling network. Identifying stress-responsive biochemical signatures may advance understanding of BD pathophysiology and contribute to the development of objective molecular biomarkers.