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 and GABAA 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
- Kim JJ, Gharpure A, Teng J, Zhuang Y, Howard RJ, Zhu S, Noviello CM, Walsh RM Jr, Lindahl E, Hibbs RE. "Shared structural mechanisms of general anaesthetics and benzodiazepines." Nature 2020: Online Sept 2. https://www.nature.com/articles/s41586-020-2654-5
- Rahman MM, Teng J, Worrell BT, Noviello CM, Lee M, Karlin A, Stowell MHB, Hibbs RE. "Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins." Neuron 2020: 106(6):952-962. PMID: 32275860.
- Gharpure A, Teng J, Zhuang Y, Noviello CM, Walsh RM Jr, Cabuco R, Howard RJ, Zaveri N, Lindahl E, Hibbs RE. "Agonist selectivity and ion permeation in the α3β4 ganglionic nicotinic receptor." Neuron 2019: 104(3):501-511. PMID: 31488329.
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ and Hibbs RE. "Structure of a human synaptic GABAA receptor." Nature 2018: 559(7712):67-72. PMID: 29950725.
- 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: 557(7704):261-265. PMID: 29720657.
- Morales-Perez CL, Noviello CM and Hibbs RE "X-ray structure of the human α4β2 nicotinic receptor." Nature 2016: 538(7625):411-415. PMID: 27698419.
- Morales-Perez CL, Noviello CM and Hibbs RE "Manipulation of subunit stoichiometry in membrane proteins." Structure 2016: 24(5):797-805. PMID: 27041595.
- Hibbs, RE, Zambon, A. “Nicotine and agents acting at the neuromuscular junction and autonomic ganglia.” Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 13th Edition. Eds. Laurence Brunton, Randa Hilal-Dandan and Bjorn Knollman. McGraw-Hill Publishing, 2018.