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 D  A  N  G    L  A  B 

How do genetic variants result in
altered brain development and epilepsy?

A recent explosion in gene discovery has revealed hundreds of genes associated with intellectual disability and epilepsy.
There is a critical need to better understand how these gene variants cause disease
in order to develop novel therapeutic strategies.
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Mission

To understand the cellular and molecular pathogenesis of genetic causes of epilepsy and brain malformations
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Vision

To build a framework for pre-clinical development of novel therapies for children affected by genetic diseases of the brain
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Values

Kindness
Integrity
Teamwork
Diversity
Curiosity

RESEARCH

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Organoid models of mTORopathies

Pathogenic genetic variants in the mechanistic target of rapamycin (mTOR) pathway can cause mTOR hyperactivity, resulting in brain malformations and epilepsy. STRADA is an upstream regulator of the mTOR pathway, and loss of STRADA causes mTOR hyperactivation, and PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy) syndrome. 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 mTOR pathway hyperactivation alter cell fate decision in early cortical development and interneuron development and cause brain malformations and epilepsy.
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Novel therapies for
​Dravet Syndrome

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 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 upstream open reading frames to amplify expression of the non-pathogenic copy of SCN1A as a therapeutic strategy.
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SCN1B-related developmental and epileptic encephalopathy

Biallelic pathogenic variants in the SCN1B gene cause a 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.​

THE TEAM

We believe that science is best advanced by
a diverse team working in an inclusive and collaborative environment
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Louis T. Dang, MD/PhD
​Principal Investigator

Pediatric epileptologist, developmental neurobiologist, rock climber

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Grace Lin, PhD
Research Specialist

Molecular biologist, chromatin expert, baker extraordinaire
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Debora VanHeyningen
​Research Specialist

Stem cell culturist, filk musician
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Tong Pan, MD
​Postdoctoral fellow

Neurologist,
confocal photographer,
​feline and caffeine lover
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Amrita Kondur
Undergraduate student

Student, matcha lover, amateur kayaker
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Aiswarya Saravanan
Undergraduate student

Student, Thai tea lover, avid reader
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Clay Walker
Research Lab Tech 



Lab Alumni


Daniel Klarr, 2016
Matthew Parent, summer 2016
Pooja Patel, summer 2017
Trevor Glenn, summer 2016 and summer 2017
Anand Chandrasekhar, 2017-2018
Alexandra (Lexie) Streicher, summer 2018 and summer 2019
Jordan Safran, 2017-2019
Monica Lee, summer 2020
Preethi Swaminathan, 2016-2020
Shivanshi Vaid, 2018-2022
Anna Loughman, 2019-2022
Daniel Jaklic, 2022-2023
​Grace Randolph, summer 2023
Sahej Kohli, 2022-2024
Saul Pantoja-Gutierrez, Summer 2024
​Alex Gamber, 2023-2025


Parent Lab, 2022
Debora VanHeyningen
Parent Lab, 2019
Parent Lab River Trip, 2018
Lexie Streicher, Trevor Glenn, Shivanshi Vaid, and Preethi Swaminathan
Preethi Swaminathan, Shivanshi Vaid, and Helen Zhang
Lexie Streicher, Trevor Glenn, Shivanshi Vaid, and Preethi Swaminathan
Preethi Swaminathan and Shivanshi Vaid
Shivanshi Vaid and Preethi Swaminathan
Preethi Swaminathan
Preethi Swaminathan
Grace Lin and Shivanshi Vaid
Shivanshi Vaid
Jordan Safran
Dan Jaklic
Dan Jaklic
Sahej Kohli
Saul Pantoja-Gutierrez

PUBLICATIONS


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  • Dang, L.T., Parent, J.M. “Genetic Epilepsy Modeling with Human Pluripotent Stem Cells.” In: Models of Seizure and Epilepsy, Second Edition. Edited by Pitkänen, A., Buckmaster, P.S., Galanopoulou, A.S., and Moshe, S.L. Elsevier publishing, 2017, 247-260.

  • 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.

  • Tidball, A.M., Swaminathan, P., Dang, L.T., Parent, J.M. Generating Loss-of-function iPSC Lines with Combined CRISPR Indel Formation and Reprogramming from Human Fibroblasts. Bio-protocol, 2018; 8(7): e2794.

  • 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. 

  • Dang, L.T., Quinonez, S.C., Becka, B.R., Isom, L.L., Joshi, S.M. Dramatic improvement in seizures with phenytoin treatment in an individual with refractory epilepsy and a SCN1B variant. Pediatric Neurology, 2020; 108:121-122. 

  • 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. 

  • 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

  • ​Pan, T., Jaklic, D.C., Vaid, S., Lin, G., VanHeyningen, D., Dang, L.T. A Multi-Electrode Array Platform for Modeling Epilepsy Using Human Pluripotent Stem Cell-Derived Brain Assembloids. Journal of Visualized Experiments (JoVE),2024; 211, e67396. doi: 10.3791/67396 PMID: 39400160


Complete list of Publications

LAB NEWS

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9/27/24
We are excited to publish a method to plate forebrain assembloids (dorsal-ventral organoid fusions) onto multielectrode array plates for recording and drug treatment in JoVE! Go check it out here! 
9/9/24
Welcome to the lab, Clay Walker! Clay worked previously at the University of Michigan in Andrew Tidball's lab  and we are excited to have Clay join! Clay is excited to learn about neural development, to work with brain organoids, and build experience to go to graduate school in neuroscience.


​5/1/23
Welcome, Dr. Tong Pan to the lab! We are excited to have Tong as the lab's first postdoc to join! She is a neurologist and physician-scientist with a background in
 novel receptors/ion channels that mediate thermosensation using C. elegans as a model. Tong is excited to learn about using stem cell derived cerebral organoid models for neurodevelopmental diseases.
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8/10/22

We are excited to have received our Notice of Award from the NIH for our R01 grant submission! A big thank you to all the mentors, collaborators, and sponsors that have contributed to this big milestone in our lab. 
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Dang Lab
Biomedical Science Research Building, Rm 5258
109 Zina Pitcher Place
Ann Arbor, MI 48109

​Email: louisdan [at] med.umich.edu
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