Gabsang Lee Ph.D, DVM
Assistant Professor of Neurology and Neuroscienceglee48@jhmi.edu
Telephone Number: 443-287-8631
Fax Number: 410-614-9568
Institute for Cell Engineering
School of Medicine
Department of Neurology and Neuroscience
733 N. Broadway BRB Suite 753
Baltimore, MD 21205
Disease modeling of peripheral neuropathies with human pluripotent stem cells
The Lee lab focuses on neural crest biology 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. To understand the neural crest specification process, he will use a genetic reporter system in hESCs to isolate neural crest sub-lineages 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 will also use 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-killer.