Welcome to the Isom Lab, established in 1995, in the Department of Pharmacology at Michigan Medicine. Our goal is to make Sudden Unexpected Death in Epilepsy (SUDEP) history by studying gene variants linked to developmental and epileptic encephalopathy, especially variants in genes encoding voltage-gated sodium channels. Our work uses human induced pluripotent stem cell neurons and cardiac myocytes as well as transgenic mouse and rabbit models. Our expertise includes electrophysiology, confocal imaging, genetics, and molecular and cellular biology techniques.

Latest News

Open postdoctoral positions in the Isom Lab!

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We are searching for postdoctoral fellows to work on our NIH-funded…

Sodium channel β1 subunits participate in regulated intramembrane proteolysis-excitation coupling

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Loss-of-function (LOF) variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are linked to human diseases with high risk of sudden death, including developmental and epileptic encephalopathy and cardiac arrhythmia. β1 Subunits modulate the cell-surface localization, gating, and kinetics of sodium channel pore-forming α subunits. They also participate in cell-cell and cell-matrix adhesion, resulting in intracellular signal transduction, promotion of cell migration, calcium handling, and regulation of cell morphology. Here, we investigated regulated intramembrane proteolysis (RIP) of β1 by BACE1 and γ-secretase and show that β1 subunits are substrates for sequential RIP by BACE1 and γ-secretase, resulting in the generation of a soluble intracellular domain (ICD) that is translocated to the nucleus. Using RNA sequencing, we identified a subset of genes that are downregulated by β1-ICD overexpression in heterologous cells but upregulated in Scn1b-null cardiac tissue, which lacks β1-ICD signaling, suggesting that the β1-ICD may normally function as a molecular brake on gene transcription in vivo. We propose that human disease variants resulting in SCN1B LOF cause transcriptional dysregulation that contributes to altered excitability. Moreover, these results provide important insights into the mechanism of SCN1B-linked channelopathies, adding RIP-excitation coupling to the multifunctionality of sodium channel β1 subunits.

Dancing to a different tune: TANGO gives hope for Dravet syndrome

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This article was written by Professor David Henshall, Director of the FutureNeuro SFI Research Centre at the Royal College of Surgeons in Ireland.

Research

Variants in ion channel genes can lead to neurological or cardiovascular diseases called channelopathies. Our work focuses on human variants in genes encoding voltage-gated sodium channel α and β subunits that lead to a devastating pediatric epileptic encephalopathy called Dravet syndrome, a disease with a high risk of Sudden Unexpected Death in Epilepsy (SUDEP). We have proposed that SUDEP arises from simultaneous arrhythmias of brain and heart due to the expression of mutant sodium channel genes in both organs.  Our ultimate goals are to discover novel targets for epilepsy therapeutics and to identify biomarkers for SUDEP risk.

Group Members

Lori L. Isom, PhD

Lori L. Isom, PhD

Chair, Department of Pharmacology, Maurice H. Seevers Collegiate Professor of Pharmacology, Professor of Molecular and Integrative Physiology, Professor of Neurology
Veronica Beck

Veronica Beck

Graduate Student, Neuroscience Program
Chunling Chen

Chunling Chen

Research Lab Specialist Lead
Yan Chen

Yan Chen

Research Lab Specialist Intermediate
Nick Denomme

Nick Denomme

Pharmacology Graduate Student
Nnamdi Edokobi

Nnamdi Edokobi

Pharmacology Graduate Student
Rene Caballero Floran, PhD

Rene Caballero Floran, PhD

Research Investigator, Department of Pharmacology
Samantha Hodges, PhD

Samantha Hodges, PhD

Michigan Postdoctoral Pioneer Program Fellow
Luis Lopez-Santiago, PhD

Luis Lopez-Santiago, PhD

Associate Research Scientist, Department of Pharmacology

lopezslf@umich.edu

Heather O’Malley, PhD

Heather O’Malley, PhD

Assistant Research Scientist, Department of Pharmacology
Roberto Ramos Mondragon, PhD

Roberto Ramos Mondragon, PhD

Research Investigator, Department of Pharmacology
Larissa Robinson-Cooper

Larissa Robinson-Cooper

Research Technician
Caroline Scheuing

Caroline Scheuing

Undergraduate Researcher
Yukun Yuan, PhD

Yukun Yuan, PhD

Research Assistant Professor of Pharmacology
Yanting Zhao, PhD

Yanting Zhao, PhD

Research Investigator, Department of Pharmacology

Publications

Click here to view Lori Isom’s publications on PubMed.

To access our new Science Translational Medicine paper with Stoke Therapeutics. “Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome,” please click on the following links:

Reprint: http://stm.sciencemag.org/cgi/rapidpdf/12/558/eaaz6100?ijkey=N5jj5tKEmu0oY&keytype=ref&siteid=scitransmed

Full text: http://stm.sciencemag.org/cgi/content/full/12/558/eaaz6100?ijkey=N5jj5tKEmu0oY&keytype=ref&siteid=scitransmed

Click here to view Lori Isom’s publications on Google Scholar.

Open Positions

POSTDOCTORAL FELLOWS
We are currently searching for postdoctoral fellows who are interested in working with mouse models of neurological or cardiac disease. If interested, please send Dr. Isom an e-mail at lisom@umich.edu.

GRADUATE STUDENTS
Dr. Isom belongs to several Michigan Ph.D. training programs, including Pharmacology, Neuroscience, CMB, and Molecular and Integrative Physiology. If interested in a research rotation, please send her an e-mail at lisom@umich.edu.

UNDERGRADUATES
Please send an e-mail with a short note about your interest in our lab, your CV, and a transcript to Dr. Isom at lisom@umich.edu.

STAFF
We currently have an open technical position for a person with expertise in histology/immunohistochemistry.  If interested, please send Dr. Isom an e-mail at lisom@umich.edu.

Photos

Contact

Isom Laboratory
Department of Pharmacology
University of Michigan Medical School

2301E MSRB III (office)
2200 MSRB III (lab)
1150 W. Medical Center Dr.
Ann Arbor, MI 48109-5632

734-936-3050 (office)
734-936-3043 (lab)

Department of Pharmacology Website: https://medicine.umich.edu/dept/pharmacology

If you’d prefer to contact the Isom Lab via email, please use the contact form below.

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Funding Partners

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