The Hibbs lab is pursuing atomic-scale mechanisms of synaptic proteins, with a current focus on ligand-gated ion channel structure and function. We are fascinated by how these complex molecules respond to binding of a small chemical neurotransmitter by triggering the opening of an intrinsic ion conduction pathway >50 Å away. This conformational conversion allows for diffusion-limited rates of ion flux and occurs on the millisecond timescale. We further seek to probe mechanisms of ion selectivity and allosteric modulation, with a long term goal of better informing rational therapeutic design for neurological disorders and addiction. We employ a multidisciplinary approach encompassing molecular biology, protein biochemistry, pharmacology, x-ray crystallography, cryo-electron microscopy and electrophysiology. Recent work from the lab has explored structural biology of heteromeric nicotinic receptors both by crystallographic and cryo-EM approaches.
Dr. Hibbs graduated from Whitman College, a small liberal arts college in Washington State, with a combined degree in Chemistry/Biochemistry. During doctoral research at the University of California, San Diego, he studied conformational changes in an ion channel ligand binding domain under the supervision of Dr. Palmer Taylor (Department of Pharmacology). As a postdoctoral fellow, he pursued structural and functional studies of an intact, eukaryotic ligand-gated ion channel in the laboratory of Dr. Eric Gouaux (HHMI/Vollum Institute). He joined the faculty in UT Southwestern Medical Center's Departments of Neuroscience (primary) and Biophysics (secondary) in 2012.
Selected Original Articles
- Walsh RM Jr, Roh SH, Gharpure A, Morales-Perez CL, Teng J and Hibbs RE. "Structural principles of distinct assemblies of the human α4β2 nicotinic receptor." Nature 2018: Epub ahead of print. PMID: 29720657.
- Morales-Perez, C.L., Noviello, C.M. and Hibbs, R.E. "X-ray structure of the human α4β2 nicotinic receptor." Nature 2016: 538(7625):411-415. PMID: 27698419.
- Morales-Perez, C.L., Noviello, C.M. and Hibbs, R.E. "Manipulation of subunit stoichiometry in membrane proteins." Structure 2016: 24(5):797-805. PMID: 27041595.
- Hibbs, R.E., Zambon, A. “Agents acting at the neuromuscular junction and autonomic ganglia.” Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th Edition. Eds. Laurence Brunton, Bruce Chabner and Bjorn Knollman. McGraw-Hill Publishing, 2011.