Lori L Isom
Affiliation: University of Michigan
Yuan Y, O Malley H, Smaldino M, Bouza A, Hull J, Isom L. Delayed maturation of GABAergic signaling in the Scn1a and Scn1b mouse models of Dravet Syndrome. Sci Rep. 2019;9:6210 pubmed publisher
..Thus, targeting the polarity of GABAergic signaling in brain may be an effective therapeutic strategy to reduce SUDEP risk in DS. ..
Frasier C, Zhang H, Offord J, Dang L, Auerbach D, Shi H, et al
. Channelopathy as a SUDEP Biomarker in Dravet Syndrome Patient-Derived Cardiac Myocytes. Stem Cell Reports. 2018;11:626-634 pubmed publisher
..Thus, the high risk of SUDEP in DS may result from a predisposition to cardiac arrhythmias in addition to seizures, reflecting expression of SCN1A in heart and brain. ..
Yuan Y, Isom L. SUMOylation of Neuronal Kâº channels: a potential therapeutic pathway for epilepsy and SUDEP?. Neuron. 2014;83:996-8 pubmed publisher
..In this issue of Neuron, Qi et al. (2014), define how hyper-SUMOylation impacts K(+) channel activity in vivo and could serve as a potential pathway for development of novel epilepsy therapeutics. ..
O Malley H, Isom L. Sodium channel Î² subunits: emerging targets in channelopathies. Annu Rev Physiol. 2015;77:481-504 pubmed publisher
..Although VGSC Î² subunit-specific drugs have not yet been developed, this protein family is an emerging therapeutic target. ..
Frasier C, Wagnon J, Bao Y, McVeigh L, Lopez Santiago L, Meisler M, et al
. Cardiac arrhythmia in a mouse model of sodium channel SCN8A epileptic encephalopathy. Proc Natl Acad Sci U S A. 2016;113:12838-12843 pubmed publisher
..Simultaneous dysfunction in these systems may contribute to SUDEP associated with mutations of Scn8a. ..
Lopez Santiago L, Yuan Y, Wagnon J, Hull J, Frasier C, O Malley H, et al
. Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy. Proc Natl Acad Sci U S A. 2017;114:2383-2388 pubmed publisher
..Our results demonstrate that Scn8a plays a vital role in neuronal excitability and provide insight into the mechanism and future treatment of epileptogenesis in EIEE13. ..
Fein A, Meadows L, Chen C, Slat E, Isom L. Cloning and expression of a zebrafish SCN1B ortholog and identification of a species-specific splice variant. BMC Genomics. 2007;8:226 pubmed
..These data add to our understanding of structure-function relationships in Na+ channel beta1 subunits and establish zebrafish as an ideal system in which to determine the contribution of scn1ba to electrical excitability in vivo. ..
Kruger L, O Malley H, Hull J, Kleeman A, Patino G, Isom L. ?1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function. J Neurosci. 2016;36:6213-24 pubmed publisher
..We conclude that this disease-causing mutation is not simply a loss-of-function, but instead results in a deleterious gain-of-function in the brain. ..
Isom L. I. Cellular and molecular biology of sodium channel beta-subunits: therapeutic implications for pain?. Am J Physiol Gastrointest Liver Physiol. 2000;278:G349-53 pubmed
..It is proposed that multifunctional sodium channel beta-subunits provide a critical link between extracellular and intracellular signaling molecules and thus have the ability to fine tune channel activity and electrical excitability...