Available to mentor
I have been a member of the research faculty in the Michigan Medicine Department of Pharmacology since 2014, currently at the Assistant rank. I am passionate about advancing opportunities for research faculty at the University of Michigan. I am a current member of the Medical School Advisory Committee on Primary Research Appointments, Promotions, and Titles (APRAPT, term 2021-2024). I have also served in central faculty governance since 2021, beginning with committees including chairing the Faculty Senate's Information Technology Committee (ITC, term 2021-2023). I am an elected member of the Senate Advisory Committee for University Affairs (SACUA, term 2023-2026) and a de facto member of the Faculty Senate Assembly. I am also a member of the University of Michigan Faculty Well-Being Collective (wellbeing.umich.edu) which aims to promote holistic well-being for all members of the University, with my personal interest being in support for mental health and healing.
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Postdoctoral FellowUniversity of Michigan, Pharmacology, 2014
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PhDUniversity of Michigan, Ann Arbor, 2009
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BScMcMaster University, Hamilton, 1997
My research interests stem from the biology of the voltage-gated sodium channel (VGSC) beta subunits. VGSCs, apart from their roles in excitability, are also key proteins implicated in multiple forms of epilepsy, and VGSC beta subunit mutations are linked to developmental and epileptic encephalopathies (DEEs). DEEs are devastating pediatric epilepsies that have multiple comorbidities including cognitive deficits, movement disorders, autism spectrum disorders, and failure to thrive. Many DEEs are pharmacoresistant, such that patients cannot be fully treated with existing therapeutics. Importantly, every patient with epilepsy carries a risk of sudden unexpected death in epilepsy (SUDEP), and the SUDEP risks for DEE patients are among the highest across all of the genetic epilepsies.
Recent work has helped to advance the potential for gene therapy treatments for DEEs. Our recent published work has investigated therapeutic use of antisense oligonucleotides, which has promising clinical applications, with current work continuing into the use of adeno-associated virus (AAV)-mediated delivery of beta subunit proteins to help overcome genetic loss-of-function or null mutations. I am excited to continue to work on ways that basic science knowledge of the function of these important proteins can help patients in clinical settings.
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Yuan Y, Lopez-Santiago L, Denomme N, Chen C, O'Malley HA, Hodges SL, Ji S, Han Z, Christiansen A, Isom LL. Brain, 2024 Apr 4; 147 (4): 1231 - 1246.Journal ArticleAntisense oligonucleotides restore excitability, GABA signalling and sodium current density in a Dravet syndrome model.
DOI:10.1093/brain/awad349 PMID: 37812817 -
Yuan Y, O'Malley H, Chen Y, Chen C, Robinson-Cooper L, Isom L. 2020 Dec 4;Proceeding / Abstract / PosterAltered excitability of the brainstem vagus nerve dorsal motor nucleus in the Scn1b null mouse model of Dravet Syndrome
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Hull JM, O'Malley HA, Chen C, Yuan Y, Denomme N, Bouza AA, Anumonwo C, Lopez-Santiago LF, Isom LL. Ann Clin Transl Neurol, 2020 Nov; 7 (11): 2137 - 2149.Journal ArticleExcitatory and inhibitory neuron defects in a mouse model of Scn1b-linked EIEE52.
DOI:10.1002/acn3.51205 PMID: 32979291 -
O'Malley HA, Isom LL. 2020 Neuronal Chloride Transporters in Health and Disease,ChapterThe role of cation-chloride co-transporters in cardiovascular and respiratory abnormalities and SUDEP
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Yuan Y, O'Malley H, Smaldino MA, Bouza AA, Hull JM, Isom LL. Scientific Reports, 2019 Dec 1; 9 (1):Journal ArticleDelayed maturation of GABAergic signaling in the Scn1a and Scn1b mouse models of Dravet Syndrome
DOI:10.1038/s41598-019-42191-0 -
Beck VC, Bouza AA, O'Malley HA, Isom LL. 2019 Dec 6;Proceeding / Abstract / PosterInvestigating the Mechanism of Gastrointestinal Dysfunction in the Scn1b Null Mouse Model of Dravet Syndrome
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Cervantes DO, Andrade-Vicenty A, Sun C, Anand S, Pope J, Dorilio JR, Sun D, Cannata A, Cianflone E, Vinukonda G, Hintze TH, O’Malley H, Isom LL, Jacobson JT, Rota M. Circulation Research, 2019 Aug 2; 125 (Suppl_1):Proceeding / Abstract / PosterAbstract 461: Sodium Influx Modulates the Modality of Cardiac Relaxation
DOI:10.1161/res.125.suppl_1.461 -
O'Malley HA, Hull JM, Clawson BC, Chen C, Owens-Fiestan G, Jameson MB, Aton SJ, Parent JM, Isom LL. Ann Clin Transl Neurol, 2019 Jun; 6 (6): 1121 - 1126.Journal ArticleScn1b deletion in adult mice results in seizures and SUDEP.
DOI:10.1002/acn3.785 PMID: 31211177