RESEARCH

VISION & FOCUS

The major goal of the Emerling Lab is to understand key lipid signaling and metabolic pathways involved in the regulation of cellular function and growth under pathological conditions such as cancer. Our research focus centers around dissecting the roles of the family of non-canonical phosphoinositide kinases, called the phosphatidylinositol-5-phosphate 4-kinase (PI5P4Ks), in cellular metabolism and organelle communication using a multi-disciplinary approach integrating human, mouse, and worm genetic models.

PHOSPHOINOSITIDE SIGNALING PATHWAYS IN CANCER

Phosphoinositides are lipid signaling molecules that through their interaction with many signaling, adhesion and cytoskeletal proteins, have essential roles in tumorigenic events. The PI5P4Ks phosphorylate the minor lipid phosphatidylinositol 5-monophosphate (PI-5-P) at the 4-position to generate distinct pools of phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2) largely on intracellular membranes. Our recent studies reveal that the PI5P4Ks and their lipid product PI-4,5-P2 are important for metabolic homeostasis by regulating autophagosome-lysosome fusion events as well as sustaining cellular bioenergetics by coordinating peroxisome-mitochondria communication. Current aims in the Emerling Lab are to further dissect the biochemical mechanisms by which the PI5P4Ks control signaling and metabolic pathways that are required for tumor cell growth and metabolism.

TARGETING PI5P4Ks FOR CANCER THERAPY

To date we have shown that the PI5P4Ks are upregulated in several cancer subtypes, and that downregulation of these enzymes inhibits tumor growth in various cancer models, making them attractive therapeutic targets for cancer. Using preclinical studies in novel genetically engineered cancer mouse models and in human cancer cells we are investigating whether targeting these enzymes will be an effective therapy for cancers, especially in the triple negative breast cancer (TNBC) subgroup where targeted therapies have not been effective.