Dr. Louis Dang is a pediatric neurologist and epileptologist who is interested in molecular mechanisms of cortical development and who aims to determine how certain genetic mutations cause severe childhood epilepsies and neurodevelopmental defects. He completed a combined M.D./Ph.D. program at the Johns Hopkins University School of Medicine and performed his graduate work in the laboratory of Dr. Nicholas Gaiano, studying how the Notch pathway regulates cell fate choices in the developing forebrain, and also how it is involved in oncogenesis. With a strong scientific interest in determining how the brain forms combined with a clinical interest in the care of children with neurological disorders, he then moved to the University of Michigan for a residency in child neurology as well as a clinical fellowship in neurophysiology. After clinical training, he completed a postdoctoral research fellowship with Dr. Jack Parent and was appointed as an Assistant Professor on the tenure track in 2019.
Areas of Interest
Recently, there has been a large amount of discovery regarding which gene mutations can cause epilepsy and neurodevelopmental disorders. While this information has resulted in a handful of specific therapies, there remains a large number of gene mutations that lack a clear mechanistic explanation of a neurodevelopmental defect. Dr. Dang’s laboratory is focused on understanding the pathophysiology of genetic causes of epilepsy and neurodevelopmental disorders by using human stem cell models in order to develop novel, precision therapies.
- Cerebral organoid model of STRADA-related epilepsy and megalencephaly. Recently, there has been a large amount of discovery regarding which gene mutations can cause epilepsy and neurodevelopmental disorders. While this information has resulted in a handful of specific therapies, there remains a large number of gene mutations that lack a clear mechanistic explanation of the neurodevelopmental defects. With our collaborators, we use human stem cell models, two- and three-dimensional neuronal cultures, multiple-electrode array recordings, and calcium imaging to determine how pathogenic variants in STRADA that result in mechanistic target of rapamycin (mTOR) pathway hyperactivity alter early cortical development and cause epilepsy.
- Amplifiying Nav1.1 expression by targeting upstream open reading frames (uORFs). One of the most prevalent developmental and epileptic encephalopathies is Dravet Syndrome, caused by heterozygous loss of function variants in the SCN1A gene. This causes a reduction of the voltage-gated sodium channel encoded by SCN1A, Nav1.1. In many genes, including SCN1A, there are translation start codons and open reading frames upstream of the primary start codon that can interfere with the efficiency of translation of the main protein product. We aim to target these uORFs to amplify the expression of the non-pathogenic copy of SCN1A as a therapeutic strategy.
- Modeling SCN1B-related developmental and epileptic encephalopathy. Biallelic pathogenic variants in the SCN1B gene cause severe developmental and epileptic encephalopathy (DEE) that can have clinical features shared with Dravet Syndrome. In collaboration with Dr. Lori Isom and Dr. Jack Parent, we differentiate patient-derived stem cells into neuronal cultures in order to explore how pathogenic variants in SCN1B cause neuronal dysfunction and epilepsy.
Severe childhood genetic epilepsies, Dravet Syndrome, Epilepsy surgery
Honors & Awards
10/2019 Phillip R. Dodge Young Investigator Award, Child Neurology Society/Foundatio
- Stanford University, B.S. in Chemistry, 2001
- Johns Hopkins University, MD, and PhD in Neuroscience, 2009
- Pediatrics, University of Michigan, 2011
- Child Neurology, University of Michigan, 2014
- Clinical Neurophysiology, University of Michigan, 2015
- Neurology, with special qualification in child neurology
Published Articles or Reviews
- Tidball, A.M., Dang, L.T., Glenn, T.W., Kilbane, E.G., Klarr, D.J., Margolis, J.L., Uhler, M.D., Parent, J.M. Rapid Generation of Human Genetic Loss-of-Function iPSC Lines by Simultaneous Reprogramming and Gene Editing. Stem Cell Reports, 2017; 9:725-31. doi: 10.1016/j.stemcr.2017.07.003 PMID: 28781079, PMCID: PMC5599229.
- Frasier, C.M., Zhang, H., Offord, J., Dang, L.T., Auerbach, D.S., Shi, H., Chen, C., Goldman, A., Eckhardt, L.L., Bezzerides, V.J., Parent, J.M., Isom, L.L. Channelopathy as a SUDEP biomarker in Dravet Syndrome patient-derived cardiac myocytes. Stem Cell Reports, 2018; 11:626-634. doi: 10.1016/j.stemcr.2018.07.012 PMID: 30146492, PMCID: PMC6135724.
- Dang, L.T., Glanowska, K.M., Iflland, P.H., Barnes, A.E., Baybis, M, Liu, Y., Patino, G., Vaid, S., Streicher, A.M., Parker, W., Kim, S., Moon, U.Y., Henry, F.E., Murphy, G.G., Sutton, M.A., Parent, J.M., Crino, P.B. Multimodal analysis of STRADA function in brain development. Frontiers in Cellular Neuroscience, 2020; 14:122. doi: 10.3389/fncel.2020.00122 PMID: 32457579, PMCID: PMC7227375.
- Dang, L.T., Vaid, S., Lin, G., Swaminathan, P., Safran, J., Loughman, A., Lee, M., Glenn, T., Majolo, F., Crino, P.B., Parent, J.M. STRADA-mutant human cortical organoids model megalencephaly and exhibit delayed neuronal differentiation. Developmental Neurobiology, 2021; 00:1-14. doi: 10.1002/dneu.22816 PMID: 33619909