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ZFIN ID: ZDB-LAB-140211-1
Baraban Lab
PI/Director: Baraban, Scott
Contact Person: Baraban, Scott
Address: University of California, San Francisco 521 Parnassus Ave., S380 San Francisco, CA 94143
Country: United States
Phone: 415/476-9473
Line Designation: s

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The Baraban Lab is interested in the cellular and molecular basis of epilepsy. Epilepsy is a potentially devastating neurological disorder afflicting nearly 2.5 million Americans. While seizures can be controlled with available medications, a large number of epilepsy patients are medically intractable. Disturbances of cortical development (long recognized as a cause of epilepsy in children) are particularly difficult to treat, little understood, and marked by severe cognitive deficits. How seizures develop and how they can be prevented are of particular interest to our laboratory. Many of our studies exploit rodent models of pediatric epilepsy and tissue surgically resected from patients with intractable forms of epilepsy. Zebrafish, a new addition to the laboratory, have expanded our interests in simple vertebrate epilepsy models. We employ a multi-disciplinary experimental approach incorporating electrophysiology, pharmacology, molecular biology, and genetics.

In thinking about an epilepsy cure, we are also pursuing genetic and progenitor (“stem”) cell strategies. These approaches promise to provide new insights into the genetic basis of seizure suppression and/or offer new strategies for cell repair in an epileptic brain.

Current Research Projects

Zebrafish and Epilepsy
Epilepsy can be acquired as a result of an insult to the brain (trauma, infection, stroke or tumor) or a genetic mutation. With recent advances in our understanding of the genetic basis for many epilepsies, hope for curative treatments and effective prevention has increased. Unfortunately, this information has not resulted in significant clinical advances and where new drug treatments have emerged, the average cost of research and development for each new drug is estimated at greater than $800 million. To approach this challenge from a different direction, we propose to leverage the distinct advantages of zebrafish as a template for a small genetically tractable vertebrate epilepsy model compatible with rapid, cost-effective and high-throughput drug screening. Identification of antiepileptic compounds using a sodium channel mutant representing Dravet syndrome is currently underway. At the same time using morpholino antisense techniques, ENU mutant and transgenic approaches, we are studying (in zebrafish) the function and molecular pathophysiology of a variety of pediatric epilepsy genes.

Epileptogenesis in a Malformed Brain
Cortical malformations are increasingly recognized as a major cause of epilepsy. Although clinical studies suggest that dysplastic neurons (e.g., cells located within a malformation) have epileptogenic properties – and surgical ablation of malformed brain regions is often effective in reducing seizure frequency – little is presently known about how seizures develop in a malformed brain. Our research addresses two fundamental questions in this field: (i) How do dysplastic neurons function and (ii) How do dysplastic cells communicate? To investigate these issues, we primarily use visualized patch-clamp electrophysiological techniques in acute brain slices. Current studies focus on genetically modified mouse models for Type-1 Lissencephaly (Lis1) and Tuberous Sclerosis Complex (TSC), as well as human tissue sections obtained at surgery from patients with focal cortical dysplasia (FCD).

GABA Progenitor Cell Therapy for Epilepsy
Transplantation of neuronal precursors into the CNS offers great promise for the treatment of neurological disease. Recent reports of multipotent neural stem or progenitor cells with the ability to disperse and differentiate into neurons in adult CNS have further raised expectations that defective brain circuits can be repaired. Using transplanted progenitors from the embryonic medial ganglionic eminence (MGE; the primary source of GABAergic inhibitory interneurons) we are exploring the possibility that these cells will influence synaptic function in the host brain and reduce hyperexcitability associated with seizures. By transplanting MGE-derived cells into epileptic mice are directly testing the therapeutic potential of this cell-based approach.

Grone, Brian Post-Doc Howard, MacKenzie Post-Doc Hunt, Jr. III, Robert Post-Doc
Potter, Wyatt Post-Doc Dinday, Matthew Research Staff

Banerji, R., Huynh, C., Figueroa, F., Dinday, M.T., Baraban, S.C., Patel, M. (2021) Enhancing glucose metabolism via gluconeogenesis is therapeutic in a zebrafish model of Dravet syndrome. Brain communications. 3:fcab004
Griffin, A., Anvar, M., Hamling, K., Baraban, S.C. (2020) Phenotype-Based Screening of Synthetic Cannabinoids in a Dravet Syndrome Zebrafish Model. Frontiers in pharmacology. 11:464
Burrows, D.R.W., Samarut, É., Liu, J., Baraban, S.C., Richardson, M.P., Meyer, M.P., Rosch, R.E. (2020) Imaging epilepsy in larval zebrafish. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 24:70-80
Liu, J., Baraban, S.C. (2019) Network Properties Revealed during Multi-Scale Calcium Imaging of Seizure Activity in Zebrafish. eNeuro. 6(1)
Griffin, A.L., Jaishankar, P., Grandjean, J.M., Olson, S.H., Renslo, A.R., Baraban, S.C. (2019) Zebrafish studies identify serotonin receptors mediating antiepileptic activity in Dravet syndrome. Brain communications. 1:fcz008
Griffin, A., Hamling, K.R., Hong, S., Anvar, M., Lee, L.P., Baraban, S.C. (2018) Preclinical Animal Models for Dravet Syndrome: Seizure Phenotypes, Comorbidities and Drug Screening. Frontiers in pharmacology. 9:573
Protas, M.E., Weh, E., Footz, T., Kasberger, J., Baraban, S.C., Levin, A.V., Katz, L.J., Ritch, R., Walter, M.A., Semina, E.V., Gould, D.B. (2017) Mutations of conserved non-coding elements of PITX2 in patients with ocular dysgenesis and developmental glaucoma. Human molecular genetics. 26:3630-3638
Grone, B.P., Qu, T., Baraban, S.C. (2017) Behavioral Comorbidities and Drug Treatments in a Zebrafish scn1lab Model of Dravet Syndrome.. eNeuro. 4(4)
Griffin, A., Hamling, K.R., Knupp, K., Hong, S., Lee, L.P., Baraban, S.C. (2017) Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain : a journal of neurology. 140(3):669-683
Hong, S., Lee, P., Baraban, S.C., Lee, L.P. (2016) A Novel Long-term, Multi-Channel and Non-invasive Electrophysiology Platform for Zebrafish. Scientific Reports. 6:28248
Kumar, M.G., Rowley, S., Fulton, R., Dinday, M.T., Baraban, S.C., Patel, M. (2016) Altered Glycolysis and Mitochondrial Respiration in a Zebrafish Model of Dravet Syndrome. eNeuro. 3(2):e0008-16
Grone, B.P., Marchese, M., Hamling, K.R., Kumar, M.G., Krasniak, C.S., Sicca, F., Santorelli, F.M., Patel, M., Baraban, S.C. (2016) Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish. PLoS One. 11:e0151148
Griffin, A., Krasniak, C., Baraban, S.C. (2016) Advancing epilepsy treatment through personalized genetic zebrafish models. Progress in brain research. 226:195-207
Grone, B.P., Maruska, K.P. (2015) Divergent evolution of two corticotropin-releasing hormone (CRH) genes in teleost fishes. Frontiers in neuroscience. 9:365
Dinday, M.T., Baraban, S.C. (2015) Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome(1,2,3). eNeuro. 2(4)
Grone, B.P., Baraban, S.C. (2015) Animal models in epilepsy research: legacies and new directions. Nature Neuroscience. 18:339-343
Baraban, S.C., Löscher, W. (2014) What new modeling approaches will help us identify promising drug treatments?. Advances in experimental medicine and biology. 813:283-94
Baraban, S.C. (2013) Forebrain electrophysiological recording in larval zebrafish. Journal of visualized experiments : JoVE. (71)
Baraban, S.C., Dinday, M.T., and Hortopan, G.A. (2013) Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment. Nature communications. 4:2410
Hunt, R.F., Hortopan, G.A., Gillespie, A., and Baraban, S.C. (2012) A novel zebrafish model of hyperthermia-induced seizures reveals a role for TRPV4 channels and NMDA-type glutamate receptors. Experimental neurology. 237(1):199-206
Chege, S.W., Hortopan, G.A., Dinday, M., and Baraban, S.C. (2012) Expression and function of KCNQ channels in larval zebrafish. Developmental Neurobiology. 72(2):186-98
Hortopan, G.A., and Baraban, S.C. (2011) Aberrant expression of genes necessary for neuronal development and notch signaling in an epileptic mind bomb zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 240(8):1964-76
Hortopan, G.A., Dinday, M.T., and Baraban, S.C. (2010) Spontaneous Seizures and Altered Gene Expression in GABA Signaling Pathways in a mind bomb Mutant Zebrafish. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(41):13718-13728
Hortopan, G.A., Dinday, M.T., and Baraban, S.C. (2010) Zebrafish as a model for studying genetic aspects of epilepsy. Disease models & mechanisms. 3(3-4):144-148
Baraban, S.C. (2007) Emerging epilepsy models: insights from mice, flies, worms and fish. Current Opinion in Neurology. 20(2):164-168