Lipid Pathways: Metabolism and Disease Mechanisms

Dysregulation of lipid homeostasis underlies a broad range of pathologies, including metabolic syndrome, cardiovascular diseases, and neurodegenerative disorders. Additionally, ligand-activated nuclear receptors such as Farnesoid X Receptor (FXR), Retinoid X Receptor (RXR), and Pregnane X Receptor (PXR) play pivotal roles in coordinating glucose, lipid, and cholesterol metabolism. Understanding the molecular mechanisms of these receptors enables the identification of therapeutic targets to restore metabolic balance in diseases like fatty liver disease, cardiovascular dysfunction, and neurological disorders. Intra- and inter-cellular lipid transport is central to maintaining lipid homeostasis, enabling the proper distribution of lipids for energy production, membrane integrity, and signaling processes. Within cells, interorganelle lipid transport ensures the precise delivery of lipids such as cholesterol, phospholipids, and sphingolipids to organelles, including the endoplasmic reticulum (ER), Golgi apparatus, and mitochondria.
These exchanges are facilitated by specialized transport mechanisms, including lipid transfer proteins (LTPs) and contact sites between organelle membranes, such as the mitochondria-associated ER membranes (MAMs). Dysregulation in lipid trafficking can disrupt membrane composition, impair organelle function, and contribute endothelial and vascular dysfunction, lipid storage disorders, and neurodegeneration. By systematically investigating enzyme promiscuity, protein interactions, nuclear receptor signaling, and lipid trafficking our lab aims to unravel novel regulatory mechanisms in lipid metabolism. Through the integration of metabolic flux studies, lipidomics, and mechanistic analyses, we seek to identify disease-relevant lipid species and pathways, ultimately driving the development of targeted therapies for metabolic and neurological disorders.