The majority of the work done within my lab over the past 30 years has focused on the structure and function of ligand-gated ion channels. These molecules mediate rapid signaling from one neuron to the next, by opening ion selective pores in the surface membrane in response to the binding of neurotransmitter released from the adjacent presynaptic terminal. The opening of these pores elicits ion flows that cause excitation or inhibition. When ligand-gated channels spend too much or too little time open, the brain cannot process information correctly. Furthermore, alterations in ligand-gated channel activity can result in overt neurological disease, including epilepsy and neurodegenerative diseases. For a number of years we examined receptors for glutamate, the major excitatory transmitter in the mammalian brain, but more recently, our work focused on P2X receptors, which are activated by extracellular ATP (adenosine 5′ phosphate), the same molecule that is the major energy source for cell metabolism.
Our primary approach is usually electrophysiology, but we also use a wide range of molecular biological, biochemical and imaging approaches both in vitro and in vivo. We currently are engaged in projects that use mice, zebrafish and fruit flies, as each organism has advantages for answering specific types of questions.
The focus of the current NIH grant directed by Professor Hume is the role of ion channels in tubulovesicles, a lysosome related organelle found in the acid secreting parietal cells of the stomach. This project was initiated in the lab of Haoxing Xu, and Professor Hume took over directing it when Professor Xu stepped aside as the PI. MCDB faculty members Mohammed Akaaboune and Wanlu Du are the co-PIs. This project uses electrophysiological, biochemical and imaging studies of cell lines in vitro, as well in vitro and in vivo studies of cells from knock-out mice generated in the Xu lab.
I had a longstanding collaboration with MCDB colleague John Kuwada, who has recently retired. Over the years, we have studied the role of a number of receptors and channels in zebrafish, and his most recent PhD student spent considerable time doing electrophysiology in my lab to understand the role of the Stac proteins in regulating synapse development and muscle development in Drosophila.
I also have ongoing collaborations with MCDB colleagues Mohammed Akaaboune and Catherine Collins concerning synaptic development that have produced five papers over the past decade. All the electrophysiology in the studies from the Collins lab was done in my lab under my supervision. I designed and supervised some of the analytical approaches used in the studies from the Akaaboune lab.
I also provided electrophysiological training to members of the lab of former MCDB colleague Orie Shafer and I am currently working with MCDB colleague Monica Dus and University of Michigan Biophysics faculty member Sarah Veatch to train their lab members in electrophysiological approaches.