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上州医科大学的标志
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研究总结

The long-term goal of the Auerbach Laboratory is to investigate the prevalence, risk factors, and mechanisms for dual electrical disturbances of the brain (seizures) and heart (arrhythmias). We are particularly interested in improving our understanding of the multi-system cascade of events that lead to Sudden Unexpected Death in Epilepsy Patients (SUDEP), 这将有可能识别出猝死症的标志.

Bedside-to-Bench-to-Bedside方法: 我们有一个多系统的大脑 & 心脏)和多尺度(分子), biochemical, cellular, organ, in vivo, and clinical) approach to investigating electrical diseases of the brain and heart. We perform patient database analyses to examine the co-prevalence and risk of seizures 和心律失常. Then using cellular and animal models of the disease we perform molecular/biochemical and electrophysiological approaches to understand the underlying mechanisms for these neuro-cardiac pathologies. Ultimately, 使用患者数据库验证了这些结果, 这样就完成了从床到台到床的完整范例.

从床头柜到床头柜的研究方法

多系统映像
Multi-System Approach to Understanding and Treating Genetic Ion Channel Diseases: The Auerbach Lab’s “Bedside-to-Bench-to-Bedside” approach to research involves clinical studies of humans with a history of electrical disturbances in the brain (seizures/epilepsy) and heart (arrhythmias). Additionally, we generated a genetic rabbit model of an inherited cardiac arrhythmia disease. It enables us to explore the underlying causes for these abnormalities by performing experiments at the molecular, biochemical, cellular, 以及整个动物的水平.  研究项目的每一个方面都能促进和激励其他方面, 创造一个富有成效的研究周期.
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临床研究项目(回顾性数据集) & 可穿戴式传感器的前瞻性记录

Millions of Americans have epilepsy and they are at a high risk of sudden death (e.g., SUDEP.不幸的是，潜在的机制仍然未知.

As cardiac events are one mechanism for SUDEP, we are starting with the heart. 癫痫的遗传模型, 我们证明了观察大脑外部是至关重要的, as these mutations lead to alterations in cardiac electrical function, 包括离子通道活性的改变, 兴奋过度, 和心律失常.

遵循从工作台到病床的范式, we reported cases of cardiac ECG abnormalities and near-lethal arrhythmias in patients with severe genetic forms of epilepsy. We use analytical tools that are well accepted in the field of cardiology, 但对癫痫和猝死症还是新手, to identify epilepsy patient populations at risk of cardiac-related SUDEP. Additionally, we use wearable technology to acquire continuous multi-system recordings, 这能让我们捕捉到医院外的事件吗. The goal is to develop a comprehensive SUDEP risk assessment tool to help identify people with epilepsy who are at risk for SUDEP, 以便采取措施防止猝死的发生.

SUDEP

临床数据库研究: Data is collected from patients during interictal baseline periods, and surrounding seizures. The Auerbach Lab studies the patients’ ECG during these time periods in hopes of identifying cardiac biomarkers for SUDEP risk.

Basic Science Projects (Cellular and Animal Models of 长QT综合征)

癫痫发作参与者的百分比图表

从患者层面开始, we demonstrated that patients with a classically studied inherited cardiac arrhythmia disease, 长QT综合征(LQTS), 癫痫发作的风险增加了吗. 然而，这些癫痫发作的根本原因尚不清楚. 我们建立了一种新的LQTS突变兔模型, 会重现LQTS患者的神经心脏病变. It enables us to conduct translational studies to investigate the mechanisms for arrhythmias and seizures in LQTS. 正在进行的实验方法是在分子层面, biochemical, 细胞电生理学, organ, 以及体内水平.

长QT综合征: We showed that there is a higher prevalence of a history of seizures/epilepsy in patients with an inherited cardiac arrhythmias disease, 长QT综合征, 与基因型阴性的家庭成员相比. Patients with 长QT综合征 Type 2 showed the highest prevalence of seizures.

基础科学形象

兔2型长QT综合征模型: The Auerbach Lab has developed multiple mutant rabbit lines that model the neuro-cardiac electrical abnormalities seen in patients with 长QT综合征 Type 2. 视频脑电图/心电图记录, 还有呼吸措施, are recorded from the rabbits to validate the model and examine the underlying mechanisms.

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家兔脑电图/心电图记录:使用临床级脑电图采集设备, the Auerbach Lab records continuous EEG/ECG recordings from up to 7 rabbits simultaneously.

Publications

最近的出版物

*通讯作者, ₶First Author

  • Ryan JM₶, Wagner KT₶, Yerram S, Concannon C, Lin JX, Rooney P, Hanrahan B, Titoff V, Connolly N, Cranmer R, DeMaria N, Xia X, Mykins B, Erickson S, Couderc JP, Schifitto G, Hughes I, Wang D, Erba G, Auerbach DS*. Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. 功能性或解离性癫痫. 癫痫:欧洲癫痫杂志，2023,ISSN 1059-1311. doi: 10.1016/j.seizure.2023.08.015
  • Singh V₶, Ryan JM₶， Auerbach DS*, It is premature for a unified hypothesis of sudden unexpected death in epilepsy: A great amount of research is still needed to understand the multisystem cascade. Epilepsia 2023. doi: 10.1111/epi.17636
  • 王晓明，王晓明，王晓明，王晓明*. The ERG1 K+ 通道及其在神经元健康和疾病中的作用. 分子神经科学前沿. 2022 May 3. doi: 3389/fnmol.2022.890368
  • Auerbach DS*, Muniz CF. [社论]拉莫三嗪的心脏安全性:仍在等待判决. Neurology. 2022年3月8日 1212/WNL.0000000000200189
  • 李建军，李建军，李建军，李建军，李建军. Identification and Successful Management of Near-Lethal Ventricular Tachycardia in 2q24 Deletion-Associated Developmental and Epileptic Encephalopathy. 扣押2021年6月doi: 1016/j.seizure.2021.06.003
  • Bosinski C, Wagner KT, Zhou, X., Liu, L., Auerbach DS*. 识别癫痫发作的多系统监测, 清醒约束家兔的心律失常和呼吸暂停.  Vis. Exp.2021 3月27日;(169)，doi: 10.3791/62256 PMID: 33843929.
  • French JA, Perucca E, Sander J, Bergfeldt L, Baulac M奥尔巴赫博士, Keezer M, Thijs R, Devinsky O, Vossler D, WeltyT. FDA Safety Warning on the Cardiac Effects of Lamotrigine: An Advisory from the Ad Hoc ILAE/AES Task Force. 癫痫病开放2021年2月25日doi: 1002/epi4.12475
  • French JA, Perucca E, Sander J, Bergfeldt L, Baulac M奥尔巴赫博士, Keezer M, Thijs R, Devinsky O, Vossler D, Welty T. FDA Safety Warning on the Cardiac Effects of Lamotrigine: An Advisory from the Ad Hoc ILAE/AES Task Force. 癫痫电流2021年3月卷6 (1)45-48 doi:1177/1535759721996344 PMID: 33641454.
  • Kim BS₶奥尔巴赫博士₶, Sadhra H, Ling FS, Godwin M, Mohan A, Yule DI, Wagner L, Rich DQ, Tura S, Morrell C, Goldenberg I, Cameron SJ. A Sex-Specific Switch in Platelet Protease-Activated Receptor Signaling Following Myocardial Infarction. 动脉粥样硬化血栓血管生物学. 2020 Nov 12 PMID: 33176447PMCID: PMC7770120.
  • DeMaria N, Selmi A, Kashtan S, Xia X, Wang M, Zareba W, Couderc JP奥尔巴赫博士*. 长QT综合征的自主神经和心脏复极不稳定性. 自主神经科学:基础 & Clinical. Epub 2020 9月6日. PMID:32942226 PMCID: PMC7704776.
  • Tylock K奥尔巴赫博士, Tang ZZ, Thornton C, Dirksen RT. Biophysical mechanisms for QRS- and QTc-interval prolongation in mice with cardiac expression of expanded CUG-repeat RNA. J. Gen. Physiol. 2020 (2): e201912450, PMCID: PMC7062505. PMID: 31968060
  • Frasier CR，张宏，Offord J, Dang LT， Auerbach DS, Shi H, Chen C, Goldman AM, Eckhardt LL, Bezzerides VJ, Parent JM, Isom LL. Channelopathy as a SUDEP Biomarker in Dravet Syndrome Patient-Derived Cardiac Myocytes. 干细胞报告. 2018. 9月11日,11 (3):626 - 634. doi: 10.1016/j.stemcr.2018.07.012. Epub 2018 8月23日. PMID: 30146492; PMCID: PMC6135724. Epub 2018/08/28.
  • Wang M, Szepietowska B, Polonsky B, McNitt S, Moss AJ, Zareba W奥尔巴赫博士. Risk of Cardiac Events Associated With Antidepressant Therapy in Patients With 长QT综合征. Am J Cardiol. 2018年1月15日;121(2):182-187. PubMed PMID: 29174490; PMCID: PMC5742310.
  • Auerbach DS*, Biton Y, Polonsky B, McNitt S, Gross RA, Dirksen RT, Moss AJ. Risk of cardiac events in 长QT综合征 patients when taking antiseizure medications. Transl Res. 2018年1月;191:81 - 92.e7. PubMed PMID: 29121487; PMCID: PMC5733703.
  • Bao Y, Willis BC, Frasier CR, Lopez-Santiago低频, Lin X, Ramos-Mondragon R奥尔巴赫博士, Chen C, Wang Z, Anumonwo J, Valdivia HH, Delmar M, Jalife J, Isom LL. 小鼠Scn2b缺失导致室性和房性心律失常. 心律失常电生理. 2016年12月9日(12) 27932425; PMCID: PMC5161227
  • Carrell ST, Carrell EM, Auerbach D, Pandey SK, Bennett CF, Dirksen RT, Thornton CA. Dmpk gene deletion or antisense knockdown does not compromise cardiac or skeletal muscle function in mice. Hum Mol Genet. 2016年8月13日;PubMed: 27522499. PMCID: PMC5291200
  • 李建军，李建军，李建军，李建军. 长QT综合征癫痫发作风险的遗传生物标志物. Neurology. 2016年10月18日;87(16):1660-1668. PubMed PMID: 27466471; PMCID: PMC5085072.

出版作品的完整列表

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