Richard K. Hite
Poly-modal Regulation of Inositol 1,4,5-triphosphate Receptors
Eukaryotic cells are defined by the presence of membrane-bound organelles that provide isolated environments for specialized cellular functions. For example, the nucleus houses the genome, the endoplasmic reticulum is responsible for lipid and protein synthesis and lysosomes carry out the degradation and recycling of large macromolecules. In order for cells to function, however, these organelles need to coordinate their activities. Our laboratory investigates how chemical signals are transmitted between these cellular compartments. We are particularly interested in understanding how the movement of ions such as H+, K+, Na+ and Ca2+ into and out of specific organelles can be used to communicate information about cellular homeostasis and ensure that all of the disparate compartments of the cell are functioning together. To better understand how the movement of ions influences cellular homeostasis, we are investigating the function of several ion channels that enable the regulated transmission of ions across various organellar membranes. We use structural and biophysical tools such as cryo-electron microscopy and patch-clamp electrophysiology to elucidate the mechanisms that govern the conductance, selectivity and gating of these channels. By understanding the mechanisms by these channels function, we can design specific genetic and chemical perturbations to characterize their roles in both normal cells and in disease states.