The Predoctoral Research and Training Fellowship supports predoctoral students with dissertation research related to epilepsy, thus strengthening their interest in establishing epilepsy research as a career direction. Graduate students must be matriculating in a full-time doctoral (Ph.D.) program with an academic career focus. Areas of interest considered include, but are not limited to neuroscience, physiology, pharmacology, psychology, biochemistry, genetics, nursing, or pharmacy may apply.

Predoctoral Research and Training Fellowships support students with epilepsy-related dissertations to strengthen their interest in epilepsy research. Graduate students pursuing a Ph.D. degree in neuroscience, physiology, pharmacology, psychology, biochemistry, genetics, nursing, or pharmacy may apply. The following eleven (11) grants were awarded to study:

  • Circuit Contributions of Adult and Seizure-Induced Neurogenesis;
  • Contribution of cilia defects to neuronal activity in developing cortex;
  • Effects of TRIP8b phosphorylation on HCN channel trafficking in epilepsy;
  • Physiological Consequence of an Epilepsy Mutation in the VGSC Beta1 Subunit;
  • Optogenetic Medial Septal Neuromodulation to Control Hippocampal Seizures;
  • Inflammation in Epilepsy Associated with Cortical Dysplasia;
  • Inflammation mechanisms in epileptogenesis after febrile status epilepticus;
  • Seizures beget seizures: Role of blood-brain barrier leakage in epilepsy;
  • Characterizing KCNQ2 mutations in severe neonatal epileptic encephalopathy;
  • Proneurotrophin signaling in epilepsy;
  • The Role of BDNF in the Maturation of Axoaxonal synapses.

Circuit Contributions of Adult and Seizure-Induced Neurogenesis

Christopher Dengler, B.S., B.A.
Ph.D. Candidate
The Children's Hospital of Philadelphia
Philadelphia, PA, United States

The birth of new neurons is a natural feature of the adult brain, but this process is profoundly dysregulated after brain injuries that precipitate epilepsy. The exact circuit contributions of new neurons in both the normal brain and the epileptic brain are unknown. The proposed studies employ optical and electrical recording techniques, as well as transgenic strategies to investigate the physiological contributions of neurogenesis to hippocampal circuit function in health and in epilepsy. Elucidation of the role of newborn neurons in epilepsy should enhance our understanding of the disease, and contribute to the development of new therapeutic avenues and insights.
Funding for this grant was supported by the American Epilepsy Society.

Contribution of cilia defects to neuronal activity in developing cortex

Sarah Guadiana, B.S.
Doctoral Candidate
University of Florida
Gainesville, FL, United States

Virtually every neuron in the brain grows a primary cilium, a 'cellular antennae' which surveys the cell's local extracellular environment. How cilia regulate CNS neuronal development and function is unclear despite a growing body of literature that links mutations in cilia genes with various manifestations such as cognitive disorders, autism and seizures. The overall goal is to bridge the gap between our understanding of ciliogenesis defects and abnormal neuronal activity and excitability underlying neuronal differentiation changes. Results from these experiments will provide insight into manifestations seen in patients with ciliopathies and may provide novel therapy targets for these human disorders.
Funding for this grant was supported by the American Epilepsy Society.

Effects of TRIP8b phosphorylation on HCN channel trafficking in epilepsy

Robert John Heuermann, B.A.
Graduate Student
Northwestern University - Chicago Campus
Chicago, IL, United States

Ion channels are specialized proteins that enable nerve cells to generate electrical signals. Our lab focuses on one particular family of ion channels named hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels. These channels serve a variety of functions in different regions of the brain, but in the hippocampus, an area we are particularly interested in that governs learning and memory, HCN channels have an inhibitory effect that reduces overall activity. Furthermore, in forms of epilepsy that affect the hippocampus, the amount of HCN channels is reduced, which contributes to the increased excitability and recurrent seizures that characterize epilepsy syndromes. Our goal is to understand the changes that occur in HCN channels during epilepsy, which may lead to preventive therapies for this debilitating disorder.

Physiological Consequence of an Epilepsy Mutation in the VGSC Beta1 Subunit

Larisa Kruger
Ph.D. Graduate Student
The Regents of the University of Michigan
Ann Arbor, MI, United States

Voltage-gated Na+ channels are ion channel pores in brain that are essential for proper neuronal firing. These channels are composed of alpha subunits, which form the pore, and beta subunits, that modulate the pore. The SCN1B gene encodes the beta1 subunit. Mutations in SCN1B are associated with Genetic Epilepsy with Febrile Seizures Plus (GEFS+). This proposal will compare two mouse models of GEFS+, both with mutations in Scn1b, to determine their mechanisms of epilepsy. This project will also use the induced pluripotent stem cell technique to study human neurons derived from a GEFS+ patient's skin biopsy. The long-term goal is to develop new epilepsy therapies. Funding for this grant was supported by the American Epilepsy Society.

Optogenetic Medial Septal Neuromodulation to Control Hippocampal Seizures

Nealen Laxpati
Predoctoral Researcher
Emory University
Atlanta, GA, United States

Many of the 50 million epilepsy patients worldwide lack effective therapy, and new deep brain stimulation techniques have only had partial success. This is in part due to the non-specificity of electrical stimulation, and inefficient stimulation parameters and anatomical targets. This project aims to control hippocampal seizures by addressing these three issues. Novel optogenetic techniques enable more specific neuronal control. This technology will be leveraged in the tetanus toxin rat model of epilepsy. It will be targeted to the medial septum, which projects onto the seizing hippocampus, to modulate focal hippocampal seizures with a known antiepileptic oscillatory rhythm, theta.Funding for this grant was supported by the American Epilepsy Society.

Inflammation in Epilepsy Associated with Cortical Dysplasia

Lena Hoan Nguyen, B.S.
Predoctoral Fellow
Baylor College of Medicine
Houston, TX, United States

Cortical dysplasia (CD), a disorder characterized by malformations of the cortex, is commonly associated with drug-resistant epilepsy. Although dysregulation of specific signaling pathways has been identified in cortical dysplasia, the mechanism underlying the associated epilepsy phenotype is not understood. Emerging evidence, including recent identification of increased inflammation in human cortical dysplasia tissue, supports an important role for brain inflammation in drug-resistant epilepsy. The purpose of this research is to investigate how brain inflammation modulates epilepsy in cortical dysplasia. A better understanding of the role of inflammation in epilepsy may lead to new treatment strategies.

Inflammation mechanisms in epileptogenesis after febrile status epilepticus

Katelin Patterson, B.A.
Graduate Student
The Regents of the University of California (Irvine)
Irvine, CA, United States

The most common type of seizure amongst children and infants are known as febrile seizures (seizures that arise with fever). Human data and animal studies suggests that febrile seizures lasting longer than 30 minutes (known as febrile status epilepticus or FSE) may lead to temporal lobe epilepsy (TLE). Therefore, understanding the processes in which a normal brain turns epileptic will allow for therapeutic interventions to prevent epilepsy. Inflammation has been implicated in the generation of epilepsy post FSE. We want to determine if inflammation is necessary for the generation of epilepsy after FSE by blocking it and testing for the presence of later seizures.

Seizures beget seizures: Role of blood-brain barrier leakage in epilepsy

Emma Soldner, B.S., B.A.
Graduate Research Assistant 
Regents of the University of Minnesota - Twin Cities
Duluth, MN, United States

Approximately 40% of epilepsy patients respond poorly or not at all to current therapies. Thus, understanding the causes and triggers of seizures may direct us to the development of new epilepsy treatments. Recently, it has been shown that seizure-induced blood-brain barrier leakage promotes further seizure activity, and that restoring barrier function reduces seizure burden in rodent models of epilepsy. Currently however, the cause of barrier leakage following seizures is unknown. The goal of this proposal is to understand the mechanism by which seizures alter blood-brain barrier permeability and to restore its function to help reduce seizure activity in epilepsy.
Funding for this grant was supported by the American Epilepsy Society.

Characterizing KCNQ2 mutations in severe neonatal epileptic encephalopathy

Baouyen Tran
Graduate Student
Baylor College of Medicine
Houston, TX, United States

Benign familial neonatal seizure (BFNS) is a rare inherited disease linked to mutations in the gene encoding the protein Kv7.2, and generally does not lead to developmental abnormalities. However, novel mutations in this gene lead to less favorable outcomes for affected individuals, which suffer from mild to severe psycho-motor impairment. The purpose of this research is to characterize the mutations that may help pinpoint other risk factors, leading to better therapies in order to reduce motor and cognitive decline. Funding for this grant was supported by the American Epilepsy Society and The Pediatric Epilepsy Research Foundation.

Proneurotrophin signaling in epilepsy

Ajay Thomas, B.S.
M.D./Ph.D. Candidate
University of Colorado Denver, AMC and DC
Aurora, CO, United States

This work, if successful, could impact positively our knowledge in the field of epilepsy since there is little known about the role of proBDNF signaling in development of epilepsy, and potentially lead to new ways of approaching therapeutic interventions for epilepsy.

The Role of BDNF in the Maturation of Axo-axonal synapses

Xinjun Wang
Ph.D. Student
University of Wyoming
Laramie, WY, United States

Chandelier cells play a key role in regulation of neural oscillation and epileptogenesis. This study will investigate on axo-axonic innervations in a model system for epileptogenesis. First, we will characterize the properties of axo-axonic inhibition in the piriform cortex of mice, using the optogenetic approach and in vitro slice electrophysiology. Second, we will examine the role of activity-dependent brain-derived neurotrophic factor (BDNF) in the maturation of axo-axonic innervations using a knock-in mouse model.

Funding for this grant was supported by the American Epilepsy Society.

Awards for: 2012 | 2011 | 2010 | 2009 | 2008

The Predoctoral Research and Training Fellowship supports predoctoral students with dissertation research related to epilepsy, thus strengthening their interest in establishing epilepsy research as a career direction. Graduate students must be matriculating in a full-time doctoral (Ph.D.) program with an academic career focus. Areas of interest considered include, but are not limited to neuroscience, physiology, pharmacology, psychology, biochemistry, genetics, nursing, or pharmacy may apply.

Predoctoral Research and Training Fellowships support students with epilepsy-related dissertations to strengthen their interest in epilepsy research. Graduate students pursuing a Ph.D. degree in neuroscience, physiology, pharmacology, psychology, biochemistry, genetics, nursing, or pharmacy may apply. The following eleven (11) grants were awarded to study:

  • Circuit Contributions of Adult and Seizure-Induced Neurogenesis;
  • Contribution of cilia defects to neuronal activity in developing cortex;
  • Effects of TRIP8b phosphorylation on HCN channel trafficking in epilepsy;
  • Physiological Consequence of an Epilepsy Mutation in the VGSC Beta1 Subunit;
  • Optogenetic Medial Septal Neuromodulation to Control Hippocampal Seizures;
  • Inflammation in Epilepsy Associated with Cortical Dysplasia;
  • Inflammation mechanisms in epileptogenesis after febrile status epilepticus;
  • Seizures beget seizures: Role of blood-brain barrier leakage in epilepsy;
  • Characterizing KCNQ2 mutations in severe neonatal epileptic encephalopathy;
  • Proneurotrophin signaling in epilepsy;
  • The Role of BDNF in the Maturation of Axoaxonal synapses.

Circuit Contributions of Adult and Seizure-Induced Neurogenesis

Christopher Dengler, B.S., B.A.
Ph.D. Candidate
The Children's Hospital of Philadelphia
Philadelphia, PA, United States

The birth of new neurons is a natural feature of the adult brain, but this process is profoundly dysregulated after brain injuries that precipitate epilepsy. The exact circuit contributions of new neurons in both the normal brain and the epileptic brain are unknown. The proposed studies employ optical and electrical recording techniques, as well as transgenic strategies to investigate the physiological contributions of neurogenesis to hippocampal circuit function in health and in epilepsy. Elucidation of the role of newborn neurons in epilepsy should enhance our understanding of the disease, and contribute to the development of new therapeutic avenues and insights.
Funding for this grant was supported by the American Epilepsy Society.

Contribution of cilia defects to neuronal activity in developing cortex

Sarah Guadiana, B.S.
Doctoral Candidate
University of Florida
Gainesville, FL, United States

Virtually every neuron in the brain grows a primary cilium, a 'cellular antennae' which surveys the cell's local extracellular environment. How cilia regulate CNS neuronal development and function is unclear despite a growing body of literature that links mutations in cilia genes with various manifestations such as cognitive disorders, autism and seizures. The overall goal is to bridge the gap between our understanding of ciliogenesis defects and abnormal neuronal activity and excitability underlying neuronal differentiation changes. Results from these experiments will provide insight into manifestations seen in patients with ciliopathies and may provide novel therapy targets for these human disorders.
Funding for this grant was supported by the American Epilepsy Society.

Effects of TRIP8b phosphorylation on HCN channel trafficking in epilepsy

Robert John Heuermann, B.A.
Graduate Student
Northwestern University - Chicago Campus
Chicago, IL, United States

Ion channels are specialized proteins that enable nerve cells to generate electrical signals. Our lab focuses on one particular family of ion channels named hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels. These channels serve a variety of functions in different regions of the brain, but in the hippocampus, an area we are particularly interested in that governs learning and memory, HCN channels have an inhibitory effect that reduces overall activity. Furthermore, in forms of epilepsy that affect the hippocampus, the amount of HCN channels is reduced, which contributes to the increased excitability and recurrent seizures that characterize epilepsy syndromes. Our goal is to understand the changes that occur in HCN channels during epilepsy, which may lead to preventive therapies for this debilitating disorder.

Physiological Consequence of an Epilepsy Mutation in the VGSC Beta1 Subunit

Larisa Kruger
Ph.D. Graduate Student
The Regents of the University of Michigan
Ann Arbor, MI, United States

Voltage-gated Na+ channels are ion channel pores in brain that are essential for proper neuronal firing. These channels are composed of alpha subunits, which form the pore, and beta subunits, that modulate the pore. The SCN1B gene encodes the beta1 subunit. Mutations in SCN1B are associated with Genetic Epilepsy with Febrile Seizures Plus (GEFS+). This proposal will compare two mouse models of GEFS+, both with mutations in Scn1b, to determine their mechanisms of epilepsy. This project will also use the induced pluripotent stem cell technique to study human neurons derived from a GEFS+ patient's skin biopsy. The long-term goal is to develop new epilepsy therapies. Funding for this grant was supported by the American Epilepsy Society.

Optogenetic Medial Septal Neuromodulation to Control Hippocampal Seizures

Nealen Laxpati
Predoctoral Researcher
Emory University
Atlanta, GA, United States

Many of the 50 million epilepsy patients worldwide lack effective therapy, and new deep brain stimulation techniques have only had partial success. This is in part due to the non-specificity of electrical stimulation, and inefficient stimulation parameters and anatomical targets. This project aims to control hippocampal seizures by addressing these three issues. Novel optogenetic techniques enable more specific neuronal control. This technology will be leveraged in the tetanus toxin rat model of epilepsy. It will be targeted to the medial septum, which projects onto the seizing hippocampus, to modulate focal hippocampal seizures with a known antiepileptic oscillatory rhythm, theta.Funding for this grant was supported by the American Epilepsy Society.

Inflammation in Epilepsy Associated with Cortical Dysplasia

Lena Hoan Nguyen, B.S.
Predoctoral Fellow
Baylor College of Medicine
Houston, TX, United States

Cortical dysplasia (CD), a disorder characterized by malformations of the cortex, is commonly associated with drug-resistant epilepsy. Although dysregulation of specific signaling pathways has been identified in cortical dysplasia, the mechanism underlying the associated epilepsy phenotype is not understood. Emerging evidence, including recent identification of increased inflammation in human cortical dysplasia tissue, supports an important role for brain inflammation in drug-resistant epilepsy. The purpose of this research is to investigate how brain inflammation modulates epilepsy in cortical dysplasia. A better understanding of the role of inflammation in epilepsy may lead to new treatment strategies.

Inflammation mechanisms in epileptogenesis after febrile status epilepticus

Katelin Patterson, B.A.
Graduate Student
The Regents of the University of California (Irvine)
Irvine, CA, United States

The most common type of seizure amongst children and infants are known as febrile seizures (seizures that arise with fever). Human data and animal studies suggests that febrile seizures lasting longer than 30 minutes (known as febrile status epilepticus or FSE) may lead to temporal lobe epilepsy (TLE). Therefore, understanding the processes in which a normal brain turns epileptic will allow for therapeutic interventions to prevent epilepsy. Inflammation has been implicated in the generation of epilepsy post FSE. We want to determine if inflammation is necessary for the generation of epilepsy after FSE by blocking it and testing for the presence of later seizures.

Seizures beget seizures: Role of blood-brain barrier leakage in epilepsy

Emma Soldner, B.S., B.A.
Graduate Research Assistant 
Regents of the University of Minnesota - Twin Cities
Duluth, MN, United States

Approximately 40% of epilepsy patients respond poorly or not at all to current therapies. Thus, understanding the causes and triggers of seizures may direct us to the development of new epilepsy treatments. Recently, it has been shown that seizure-induced blood-brain barrier leakage promotes further seizure activity, and that restoring barrier function reduces seizure burden in rodent models of epilepsy. Currently however, the cause of barrier leakage following seizures is unknown. The goal of this proposal is to understand the mechanism by which seizures alter blood-brain barrier permeability and to restore its function to help reduce seizure activity in epilepsy.
Funding for this grant was supported by the American Epilepsy Society.

Characterizing KCNQ2 mutations in severe neonatal epileptic encephalopathy

Baouyen Tran
Graduate Student
Baylor College of Medicine
Houston, TX, United States

Benign familial neonatal seizure (BFNS) is a rare inherited disease linked to mutations in the gene encoding the protein Kv7.2, and generally does not lead to developmental abnormalities. However, novel mutations in this gene lead to less favorable outcomes for affected individuals, which suffer from mild to severe psycho-motor impairment. The purpose of this research is to characterize the mutations that may help pinpoint other risk factors, leading to better therapies in order to reduce motor and cognitive decline. Funding for this grant was supported by the American Epilepsy Society and The Pediatric Epilepsy Research Foundation.

Proneurotrophin signaling in epilepsy

Ajay Thomas, B.S.
M.D./Ph.D. Candidate
University of Colorado Denver, AMC and DC
Aurora, CO, United States

This work, if successful, could impact positively our knowledge in the field of epilepsy since there is little known about the role of proBDNF signaling in development of epilepsy, and potentially lead to new ways of approaching therapeutic interventions for epilepsy.

The Role of BDNF in the Maturation of Axo-axonal synapses

Xinjun Wang
Ph.D. Student
University of Wyoming
Laramie, WY, United States

Chandelier cells play a key role in regulation of neural oscillation and epileptogenesis. This study will investigate on axo-axonic innervations in a model system for epileptogenesis. First, we will characterize the properties of axo-axonic inhibition in the piriform cortex of mice, using the optogenetic approach and in vitro slice electrophysiology. Second, we will examine the role of activity-dependent brain-derived neurotrophic factor (BDNF) in the maturation of axo-axonic innervations using a knock-in mouse model.

Funding for this grant was supported by the American Epilepsy Society.

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