Basic and Pre-Clinical Research
Basic and pre-clinical research involves studies primarily carried out in cells and animals and forms the basis for therapeutic drug development. The Foundation is fortunate to work with so many exceptional scientists and insitutions who are commited to STXBP1 research.
STXBP1 Translational and Pre-Clinical Research
Below is a list of research groups who are working to better understand the underlying biology of STXBP1 related disorders and develop new types of therapeutics
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Mingshan Xue is the Caroline DeLuca scholar and Assistant Professor, Department of Neuroscience, Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. Dr. Xue’s lab is studying the relationship between synaptic excitation and inhibition in the brain. His lab has developed mouse models of STXBP1 encephalopathy, to understand why not having enough STXBP1 causes seizures, behavioral and cognitive deficits.
Learn More:
https://www.bcm.edu/research/labs/mingshan-xue
https://cainlabs.texaschildrens.org/node/16
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Dr. Mike Boland is an Assistant Professor of Molecular Sciences and Director, Cellular Models of Disease, and a parent of a child with STXBP1 disorder. He uses patient-derived iPSC cell and genetic mouse models to better understand neuronal subtype deficits associated with STXBP1 encephalopathy and develop genetic therapies.
Dr. Wayne Frankel is Professor of Genetics and Development and Director of Preclinical Disease Models. His lab is focused on understanding the basis of developmental epileptic encephalopathies, using specific genetic mouse models, and developing genetic therapies.
Dr. Christopher Makinson is an Assistant Professor of Neurological Sciences. He uses genomic engineering of hiPSC cells to better understand the relationship between specific gene variants and epilepsy.
Together, this group is increasing our understanding of the pathogenic mechanisms underlying STXBP1 disorders and using this knowledge to develop new genetic therapies.
Learn More:
https://www.igm.columbia.edu/research-labs/boland-lab
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The Epilepsy Multiplatform Variant Prediction (EpiMVP) Center Without Walls is a multi-center collaborative project, funded by the National Institute of Neurological Disorders and Stroke (NINDS), involving 6 institutions; The University of Michigan, St Jude Children’s Research Hospital, Northwestern University, University of Miami, Weill Cornell Medicine, and the University of California San Francisco. It specifically is evaluating variants of unknown significance (VUS) of genetic epilepsies to develop a predictive model to aid in determining pathogenic versus benign variants to assist medical professionals and scientists. STXBP1 is one of the genes that is being researched.
More information: https://epimvp.med.umich.edu/about/
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Chris Hopkins is Chief Scientific Officer at Nemametrix. Dr. Hopkins and his group have developed humanized worm and zebrafish models to study the pathogenicity of specific genetic variants, and the relationship to phenotype. Dr. Hopkins’ interest in STXBP1 started during his graduate work, and STXBP1 is a model gene for the development of Nemametrix’s Precisome platform. Applications of Precisome include variant analysis and potential drug screening.
Learn More:
https://invivobiosystems.com/in-vivo-solutions/custom-invivo-testing/
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Scott Barban is Professor, Neurological Surgery at the UCSF Weill Institute for Neurosciences. Dr. Baraban’s lab has developed zebrafish models of several genetic epilepsies including STXBP1 encephalopathy. These zebrafish models are being used to test potential therapeutic drugs.
Learn More: https://barabanlab.ucsf.edu/
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Dr. Federico Zara is the Head of Laboratory of Neurogenetics, and Dr. Pasquale Striano is Pediatric Neurologist, both at IRCCS Istituto Giannina Gaslini and the University of Genova. They are investigating a genetic therapy approach called SINEUPs for STXBP1 disorders.
Learn More:
Ganna Balagura’s webinar presentation from September 2020 (advance to 35:42)
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Dr. Camila Esguerra is Group Leader of the Chemical Neuroscience Group and Adjunct Associate Professor, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo. Dr. Esquerra and her group use zebrafish as a model to study brain function in health and disease. The Esquerra lab seeks to understand the mechanisms of seizure generation, epileptogenesis and treatment resistance by probing the function of novel disease-associated gene variants involved in the etiology of pharmacoresistant epilepsies. One of the projects in Dr. Esquerra’s lab is to identify small molecules that may rescue STXBP1 function using a zebrafish model.
Learn More:
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Dr. Benjamin Prosser is an Assistant Professor of Physiology at Penn and a parent of a child with STXBP1 disorder. He has developed a new research collaboration with Dr. Beverly Davidson, the Director of the Center for Cellular and Molecular Therapeutics at CHOP, and Dr. Helbig in ENGIN at CHOP. Together they are working toward new genetic therapies for STXBP1 disorders, focusing on the use of anti-sense oligonucleotides (ASOs) to correct for deficiencies in STXBP1 gene expression. The group is currently testing promising compounds in iPSCs generated from patients with STXBP1 disorders.
Learn more:
https://hosting.med.upenn.edu/prosserlab/
Dr. Prosser’s webinar from September 2020
Poster and Ingo Helbig’s presentation from SIFM 2019 (advance to 14:45)
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Dr. Matthijs Verhage is the Head of the Department of Functional Genomics at the Center for Neurogenomics and Cognitive Research at the VUmc in Amsterdam. Dr. Verhaje has published over 40 papers on the cellular function of STXBP1 in the brain, and his team performs basic, translational and clinical research. Dr. Verhage’s lab has developed model systems for mice and human neurons. Current work includes understanding the excitation and inhibition imbalance in STXBP1 disorder as well as “bench to bedside” studies of specific patient phenotypes and the exact genetic patient profile, using iPSC cells.
Learn More:
https://fga.cncr.nl/people/verhage_m_-_professor
https://stxbp1.cncr.nl/our_research
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Dr. Jacqueline Burre is the Assistant Professor of Neuroscience, Feil Family Brain & Mind Research Institute at Weill Cornell Medicine in New York. Dr. Burre’s lab studies early pathological events at the neuronal synapse that trigger neurological disorders and neurodegeneration. The Burre lab has developed in vitro models including iPSC cell models to investigate STXBP1. Her lab has identified potential small molecule therapy candidates that act as “molecular chaperones” to restore the structure of the STXBP1 protein. A clinical trial pilot for one of these small molecules, 4-phenylbutyrate, is currently being designed.
Learn More:
https://appel.weill.cornell.edu/labs/burr%C3%A9-laboratory
Research Roundtables
The Foundation hosts or co-hosts an annual Research Roundtable with its collaborators. To listen to presentations from previous meetings, please click here.