Articles by Kyle A. Lyman in JoVE
Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b Ye Han*1, Kyle A. Lyman*1, Matt Clutter2, Gary E. Schiltz3, Quratul-Ain Ismail1, Xiangying Cheng1, Chi-Hao Luan4, Dane M. Chetkovich1,5 1Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine, Northwestern University, 2Center for Molecular Innovation and Drug Discovery, Northwestern University, 3Department of Pharmacology, Feinberg School of Medicine, Northwestern University, 4High Throughput Analysis Laboratory, Department of Molecular Biosciences, Northwestern University, 5Department of Physiology, Feinberg School of Medicine, Northwestern University The interaction between HCN channels and their auxiliary subunit has been identified as a therapeutic target in Major Depressive Disorder. Here, a fluorescence polarization-based method for identifying small molecule inhibitors of this protein-protein interaction, is presented.
Other articles by Kyle A. Lyman on PubMed
Reduction of Thalamic and Cortical Ih by Deletion of TRIP8b Produces a Mouse Model of Human Absence Epilepsy Neurobiology of Disease. Jan, 2016 | Pubmed ID: 26459112 Absence seizures occur in several types of human epilepsy and result from widespread, synchronous feedback between the cortex and thalamus that produces brief episodes of loss of consciousness. Genetic rodent models have been invaluable for investigating the pathophysiological basis of these seizures. Here, we identify tetratricopeptide-containing Rab8b-interacting protein (TRIP8b) knockout mice as a new model of absence epilepsy, featuring spontaneous spike-wave discharges on electroencephalography (EEG) that are the electrographic hallmark of absence seizures. TRIP8b is an auxiliary subunit of the hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, which have previously been implicated in the pathogenesis of absence seizures. In contrast to mice lacking the pore-forming HCN channel subunit HCN2, TRIP8b knockout mice exhibited normal cardiac and motor function and a less severe seizure phenotype. Evaluating the circuit that underlies absence seizures, we found that TRIP8b knockout mice had significantly reduced HCN channel expression and function in thalamic-projecting cortical layer 5b neurons and thalamic relay neurons, but preserved function in inhibitory neurons of the reticular thalamic nucleus. Our results expand the known roles of TRIP8b and provide new insight into the region-specific functions of TRIP8b and HCN channels in constraining cortico-thalamo-cortical excitability.