Aquaporin Channel Physiology and Drug Discovery Laboratory

Aquaporins (AQPs) are membrane channels that allow water and solute movement across specialized cells and tissues. Our research focuses on AQPs in the mammalian nervous system that enable essential fluid homeostasis, and a fly homolog, Big Brain, required in early nervous system development. Our interdisciplinary research team uses molecular biology, electrophysiology, cell culture, and imaging to assess the links between AQP three-dimensional protein structure and channel function, and to dissect the sophisticated roles of these channels as water pores and ion channels. Site-directed mutagenesis and voltage clamp of cloned AQPs expressed in frog oocytes are being used to define the barriers and gates in AQP permeation pathways. Little is known regarding the pharmacology of AQPs. Using clues from clinical literature and herbal lore, theoretical modeling, and experimental testing, our lab has discovered lead compound blockers for AQP1 and AQP4 with potential significance in cerebral edema, hydrocephaly, and glaucoma. Opportunities to contribute to ongoing work involve characterization of mechanisms of AQP and BIB channel regulation, analyses of AQPs in signaling complexes, drug discovery of new blocking compounds, definition of the molecular binding pockets, and exploration of these novel pharmacological tools to probe physiological significance of AQPs in health and disease.