The Lee lab focuses on neural crest and skeletal muscle lineages using human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC). Neural crest cells emerge in early development and they are a multipotent population that can give rise to more than 30 different cell types. Human myogenesis has not been studies in great details. To understand the neural crest and skeletal muscle specification process, his lab is employing multiple genetic reporter system in hESCs to isolate specific subsets to get purified cell types, which will be used to study development and disease progression.
Previously, Lee studied neural crest stem cells created from fibroblasts of patients with Familial Dysautonomia (FD), also known as Riley-Day syndrome, an inherited genetic condition that affects the peripheral nervous system. Although researchers know that FD is caused by a single point mutation in the IKBKAP gene, they do not know why symptoms, like inability to feel pain and changes in temperature, manifest. He found that FD neural crest cells expressed low levels of genes needed to make autonomous neurons—the ones needed for the “fight-or-flight” response. The FD neural crest cells also moved around less than normal neural crest cells. In an effort to discover novel drugs to treat FD, he performed high throughput screening of 7,000 compounds using FD patient-derived neural crest stem cells to look for compounds that increased gene expression and protein levels of autonomous neuron developmental components. A few compounds tested partially rescued the FD neural crest stem cell phenotypes. From this work, Lee will establish FD neurons from patient’s cells to determine how and why these neurons die. He will use the high throughput drug core from the Department of Pharmacology and Molecular Sciences to look for drugs that prevent FD-specific neuronal cell death and find novel treatments for the disease.
Lee established a protocol using hiPSCs to create Schwann cells, the neurons’ helper cells that create the myelin sheaths that insulate neurons. He will use this protocol to great Schwann cells from patients with Charcot-Marie-Tooth 1A (CMT1A)—the most common genetic disorder of the peripheral nervous system that causes demyelination of neurons that results in loss of muscle and sensation. Although CMT1A is a relatively rare disease, the results and benefits from these studies may be applied to other peripheral nerve diseases or neuropathies.
Lee lab is also using patients’ cells to study Congenital Insensitivity of Pain and Anhidrosis (CIPA), a condition that affects the pain sensing nociceptive neurons and prevents patients from feeling pain, heat and cold. Lee will study the pathogenesis of the disease and search for potential treatments. Understanding this disease and how nerves detect pain may also lead to the development of better pain killers.
Currently they are expanding their research efforts on skeletal muscle disorders, Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy.
- Efficient Generation Human Induced Pluripotent Stem Cells from Human Somatic Cells with Sendai-virus. Choi IY, Lim H, Lee G. J Vis Exp. 2014 Apr 23;(86). doi: 10.3791/51406. PMID: 24798302
- Dual-SMAD Inhibition/WNT Activation-Based Methods to Induce Neural Crest and Derivatives from Human Pluripotent Stem Cells. Chambers SM, Mica Y, Lee G, Studer L, Tomishima MJ. Methods Mol Biol. 2013 Dec 4. [Epub ahead of print] PMID: 24301074
- Candidate ALS therapeutics motor toward "in vitro clinical trials". Kim YJ, Lee G. Cell Stem Cell. 2013 Jun 6;12(6):633-4. doi: 10.1016/j.stem.2013.05.009. PMID: 23746968
- Modeling neural crest induction, melanocyte specification, and disease-related pigmentation defects in hESCs and patient-specific iPSCs. Mica Y, Lee G, Chambers SM, Tomishima MJ, Studer L. Cell Rep. 2013 Apr 25;3(4):1140-52. doi: 10.1016/j.celrep.2013.03.025. Epub 2013 Apr 11. PMID: 23583175
- Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression. Lee G, Ramirez CN, Kim H, Zeltner N, Liu B, Radu C, Bhinder B, Kim YJ, Choi IY, Mukherjee-Clavin B, Djaballah H, Studer L. Nat Biotechnol. 2012 Dec;30(12):1244-8. doi: 10.1038/nbt.2435. Epub 2012 Nov 25. PMID: 23159879
The Lee Lab
Stem Cell Core Facility