Epilepsy research is significantly underrepresented in University Seminar Series and Grand Rounds that take place at institutions across the country. In an effort to spread news about innovative research in epilepsy, CURE is pleased to sponsor a University-based invited lectureship program – Frontiers in Research. The goal of this program is to expose young researchers and clinicians to exciting epilepsy research, and to provide opportunities for young investigators to interact with a senior level epilepsy researcher.
CURE will support each sponsored lecture with a gift of $2,500 USD* to offset costs associated with hosting a seminar. Such costs include: travel expenses for one epilepsy investigator to the host institution for a visit of up to 2 nights, a meal with the speaker and students/postdocs/fellows, a meal with speaker and faculty, and material expenses involved with seminar set-up and execution.
*Incremental support of up to $500 USD may be available when international travel is involved. Requests will be handled on a case-by-case basis. Please contact Liz Higgins (Liz@CUREepilepsy.org) for more information.
Join us on the journey to discover new treatments and therapies that will lead to a CURE
Where: Northwestern University Feinberg School of Medicine
When: Monday, March 21, 2016: 12:00 – 1:00 PM CT
Speaker: Heather Mefford, MD, PhD
Host: Alfred L. George, Jr., MD & Stephan Schuele, MD
TALK SUMMARY: The introduction of next-generation sequencing technologies in the past 10 years has accelerated our understanding of the genetic architecture of the epilepsies. A significant advance has been the recognition that the epileptic encephalopathies - the most severe of the epilepsy syndromes - are often due to de novo mutations. Numerous genes have been identified in the past decade through both targeted and whole exome sequencing approaches. Dr Mefford will provide an overview of recent advances in gene discovery, with an emphasis on the encephalopathies. Proteins encoded by genes in which mutations cause epilepsy function in a wide variety of cellular processes. Understanding the genetic etiology of disease in patients may lead to more precise therapies as drugs are developed to target specific pathways and processes.
Where: University College London (UCL) School of Pharmacy
When: Friday, April 8, 2016: 12:30 – 1:30pm GT
Speaker: John Huguenard, PhD
Host: Mala M. Shah, PhD
TALK SUMMARY: Our understanding of the local and extended neural networks implicated in seizure genesis has greatly expanded in recent decades. This, coupled with advances in targeted control (opto- or chemo-genetics), is leading to rather sudden improvement of epilepsy treatment, so far at least in animals. Prof. Huguenard's presentation will describe their work in post-lesional (stroke) epilepsy models as well as genetic generalized epilepsy models (absence epilepsy), with identification and effective therapeutic targeting of key neuronal cell types.
Where: University of Connecticut Health Center (Low Learning Center)
When: Tuesday, April 26, 2016: 4:00 – 5:00pm ET
Speaker: Jack Parent, MD
Host: Eric Levine, PhD
TALK SUMMARY: Reprogramming somatic cells to a pluripotent state via the induced pluripotent stem cell (iPSC) method offers an unparalleled approach for neurological disease modeling using patient-derived neurons. My lab has applied the iPSC approach to model severe childhood genetic epilepsies with patient-derived cells. We initially generated patient-derived neurons to study epilepsy mechanisms in Dravet Syndrome (DS), a catastrophic childhood epilepsy caused by de novo dominant mutations in the SCN1A gene that encodes the voltage-gated sodium channel Nav1.1. The talk will describe our findings of altered sodium currents and excitability in DS patient neurons. I will also discuss studies in which we generated DS patient-derived cardiac myocytes to explore potential mechanisms of SUDEP (Sudden Unexpected Death in Epilepsy), which occurs at increased frequency in DS. We compared findings from electrophysiological recordings of DS iPSC-derived cardiac myocytes with those of cardiac myocytes from a DS knock-in mouse model. In the last part of the seminar, I will describe recent work examining potential epilepsy mechanisms in another ion channelopathy, the severe childhood epilepsy known as SCN8A-Associated Epilepsy. Compared to control iPSC neurons, mutant SCN8A patient-derived neurons show increased persistent sodium current and hyperexcitability. Using a multi-well multielectrode array for drug screening, we are validating the model with drugs known to work or to be ineffective in patients with SCN8A-Associated Epilepsy. Taken together, our work suggests that the iPSC approach offers great promise for modeling childhood epileptic encephalopathies and should provide a useful platform to identify novel therapies.
Where: Baylor University (Baylor Science Building, Room C105)
When: Wednesday, April 27, 2016: 3:30 – 4:30pm CT
Speaker: Amy Brooks-Kayal, MD
Host: Joaquin Lugo, PhD
TALK SUMMARY: 1 in 26 Americans will be impacted by epilepsy at some point in their lives. Although there are many symptomatic anti-seizure medications, none of them change the course of the disease or treat the underlying causes of the epilepsy. Many types of brain injuries are known to lead to epilepsy, but there are currently no preventative therapies that reduce the rate or severity of epilepsy development in those at risk. Many types of epilepsy worsen over time, but there are no therapies that can inhibit this progression. A number of novel strategies are in preclinical development for prevention and treatment of epilepsy, some of which raise the possibility of providing disease modification, prevention or even cure for this disorder. Signaling pathways offer promising targets for novel treatment strategies, some of which use existing medications. In this seminar I will discuss alterations in JAK/STAT pathway regulation of GABA(A) receptor expression and effects of JAK/STAT inhibition on epilepsy development and behavioral outcomes after experimental brain insults including status epilepticus and traumatic brain injury, and discuss the potential of JAK/STAT inhibitors as disease modifying agents for acquired epilepsies.
Where: Vollum Institute, Oregon Health and Science University (M1441, Vollum Institute seminar room)
When: Wednesday, May 18, 2016: 10:00 – 11:00 AM PT
Speaker: Jeff Noebels, MD, PhD
Host: Gary L. Westbrook, MD, Senior Scientist and Co-Director, Vollum Institute
TALK SUMMARY: Monogenic causes of epilepsy now exceed one hundred genetic loci and give rise to a diverse biological spectrum of neural network synchronization disorders in the developing brain. The aberrant circuit excitability gives rise to clinically distinctive syndromes manifested by different seizure types and comorbidities, including autism, cognitive deficits, and even premature mortality. Sudden unexplained death in epilepsy (SUDEP) is the most common cause of death in idiopathic epilepsy and second only to stroke in the number of human life years lost. Until recently the underlying mechanisms were unknown. Studies in our laboratory have definitively linked mutations in ion channel genes for human cardiac arrhythmias with epilepsy and sudden death, providing the first validated genetic biomarker for SUDEP risk in individuals with epilepsy. New research in genetically engineered mouse models of SUDEP now demonstrates that a slow depolarizing wave, similar to that underlying the aura of blindness and hemiplegia that precede some genetic forms of migraine headache, is triggered following a seizure and silences brainstem pacemaker regions in the dorsal medulla causing cardiorespiratory collapse. Genes and mechanisms for migraine with aura are now also implicated in sudden death.
Where: University of Vermont Medical Center (Davis Auditorium)
When: Friday, May 20, 2016: 12:00 – 1:00pm ET
Speaker: Scott Baraban, PhD
Hosts: Gregory L. Holmes, MD & Rodney Scott, MD, PhD
TALK SUMMARY: Zebrafish (Danio rerio) have emerged as a promising and valuable model organism. The increasing popularity of this small vertebrate is evident from the growing numbers of publications, and new discoveries associated with the use of zebrafish for studying development, brain function, human disease and drug screening. Owing to the development of novel technologies, the range of zebrafish research possibilities is constantly expanding with new imaging, electrophysiological, and gene editing tools enhancing traditional techniques. Despite the widespread success of zebrafish in the neuroscience community, epilepsy research using this organism is more limited. To address this issue, we began to adapt zebrafish for epilepsy related studies in the mid-1990s. Similar to rodents, these early studies utilized chemoconvulsants and monitored wild-type zebrafish larvae for changes in behavior, electrical activity and early gene expression. With the rapidly expanding molecular and neuroscience tool box, we are now using zebrafish models mimicking human pediatric epilepsies with genetic causes. These genetically modified zebrafish are amenable to rapid drug screening, long-term EEG monitoring or whole-brain calcium imaging, and hold great potential to advance our understanding and treatment of epilepsy. In this lecture, I will highlight the past and present techniques which have made, and continue to make, zebrafish an attractive model organism in epilepsy research. I will also focus on scn1 mutant zebrafish mimicking a catastrophic form of pediatric epilepsy known as Dravet syndrome, and our efforts to screen repurposed drug libraries to identify novel lead compounds for this disorder.
Where: University of Wisconsin-Madison
When: Wednesday, May 25, 2016: 12:00 – 1:00pm CT
Speaker: Paul Buckmaster, DVM, PhD
Host: Matt Jones, PhD
TALK SUMMARY: What causes temporal lobe epilepsy? The dentate gyrus in patients with temporal lobe epilepsy displays many functional and structural abnormalities. Some possibilities include synaptic reorganization, aberrant hub cells, and dysfunction or loss of inhibitory interneurons. Which (if any) are most responsible for generating spontaneous seizures? Recent anatomical and electrophysiological results from animal models of temporal lobe epilepsy will be presented.
Where: Stanford University (Munzer Auditorium in the Beckman Building)
When: Friday, June 24, 2016: 12:00 – 1:00pm PT
Speaker: Eleanora Aronica, MD, PhD
Host: John Huguenard, PhD
TALK SUMMARY: The role of inflammation in the pathophysiology of human epilepsy has received increasing attention in recent years. Accumulating evidence suggests that activation of both innate and adaptive immune system occurs in human epilepsy and that the inflammatory response may contribute to the generation of seizures and to seizure-related neuronal damage. Both clinical observations in drug-resistant human epilepsies and experimental findings in clinical relevant models will be discussed, highlighting specific inflammatory pathways that could represent potential targets for antiepileptic, disease-modifying therapeutic strategies. Attention has been recently focused on the role of microRNAs (miRNA) in the regulation of the innate and adaptive immune responses. Specific miRNAs play a key role in regulating inflammatory pathways involved in epilepsy and represent attractive targets for further preclinical studies in neurological disorders associated with a chronic deregulation of the inflammatory response.
Where: Bhutan Society of Epilepsy and Neurology, Thimphu (Bhutan)
When: Monday, July 25, 2016: 11:00-12:00 AM
Speaker: Dr. Manjari Tripathi
Host: Dr. Devender Bhalla
TALK SUMMARY: It is estimated that the epilepsy affects approximately 50 million people, around 40 million of them living in developing countries (World Health Organization, 2000). 80% of the burden of epilepsy is in the developing world, where in some areas 80% to 90% of people with epilepsy receive no treatment at all. This higher incidence rates in developing countries, is thought to be attributable to parasitosis particularly neurocysticercosis, HIV, trauma, perinatal morbidity, and consanguinity. The diagnosis of epilepsy is clinical but is also helped by videos made by the caregiver showing the complete seizure. Complimentary tests include EEG, CT head, MRI Brain. 70 % of persons with epilepsy respond to first line medicines used in combination. The most common medicines used are Phenytoin, carbamazepine and valproic acid. Newer drugs like levitiracetam, lamotrigine, topiramate, clobazam, lacosamide are also effective and may have a better adverse effect profile. When people with epilepsy continue to have frequent seizures despite multiple-drug therapy, epilepsy surgery may be indicated. Surgery can provide a significant improvement in the quality of life for some of the 20% to 30% of people with epilepsy who continue to have seizures while taking appropriate medication. A video EEG, MRI brain epilepsy protocol, PET, SPECT may be required before epilepsy surgery. Special diets are also an effective method specially in children. My talk will cover the diagnosis of epilepsy and management approach.
Halifax, Nova Scotia
Where: Dalhousie University
When: Wednesday, September 21, 2016
Speaker: Helen Scharfman, PhD
Host: Bernd Pohlmann-Eden, MD, PhD
TALK SUMMARY: It has been suggested that neuronal hyperexcitability contributes to Alzheimer's disease (AD), based on the observations of seizures in both clinical studies and animal data. In animals it has been shown that robust seizures exist in mice that have mutations in the genes that regulate amyloid beta and tau, the two molecules that are considered to be central to AD neuropathology. Nevertheless, the exact relationship between hyperexcitability and AD is still unclear. In this presentation we will review clinical and basic research studies to date, and then discuss recent experiments of our laboratory that focus on the earliest ages of two mouse models where amyloid beta is increased due to mutations in its precursor (amyloid precursor protein, APP) that either mimic a Swedish or London cohort with AD. We also have examined a transgenic mouse with APP overexpression without any mutation, and a mouse model of Down’s syndrome, where APP is increased and AD develops in almost all individuals. Together our data suggest that one of the earliest characteristics of these mouse models and Down's syndrome are interictal spikes that can be recorded in widespread regions of the hippocampus and cortex. The spikes occur during sleep initially but then develop in other behavioral states as well. The mechanisms, use of spikes as a biomarker, and the therapeutic benefit of blocking spikes will be discussed.
CURE’s goal in developing this lectureship program is to attract the best and brightest minds into the field of epilepsy research. Approximately 10 seminars will be sponsored at different institutions each academic year with one goal – to present cutting-edge epilepsy research to a wide audience of researchers, clinicians, young investigators, and students.
If you have any questions about the Frontiers in Research Seminar Series program, please contact Liz Higgins at Liz@CUREepilepsy.org