Dr. David Wang earned his M.D. (1998) and Ph.D. (2001) from Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, where he studied the function of purinergic receptors in the peripheral nerve regeneration. He received his postdoctoral training at the National Institute of Environmental Health Science (NIEHS), studying the role of microglial activation in the pathogenesis of Parkinson’s disease (PD) and inhibition of microglial activation using natural herb derivatives as therapies for PD.
As a Research Associate in the Johns Hopkins University School of Medicine, Dr. Wang further pursued the role of inflammation in neurological disorders by delineating that granzyme B, released from activated T-cells, inhibits neuronal differentiation of neural stem cells and causes neurotoxicity by activating PAR-1 receptor and Notch-1. Dr. Wang joined NINDS in 2011 as the lead scientist in Neural Differentiation Unit, Translational Neuroscience Center, directed by NINDS Clinical Director, Dr. Avindra Nath. In consultation with Dr. Nath, Dr. Wang helps develop 2D and 3D neural differentiation models using iPSCs and induced neural stem cells derived from minimum patient blood samples to study the mechanism of neural development and the pathogenesis of neural disorders, especially on delineating the genetic and epigenetic modifications leading to motor neuron degeneration.
Genetic background, epigenetic modifications and environmental factors all participate in neural degeneration in central nervous system. Retrovirus infection plays a crucial role in human evolution by transmitting genetic information among species. The inheritable incorporation of retrovirus sequences in human genome resulted in human endogenous retrovirus (HERV), which inhibition and reactivation mingles with neuronal development as well as neurodegeneration. Using 2D and 3D neuronal differentiation models, Dr. Wang studies the role of HERV-K in human neural development and in the pathogenesis of human motor neurons and how epigenetic modifications of DNA mediate the function of HERV-K. He is also interested in differentiating the roles of glial, endothelial and neuronal cells in neurodegeneration.
In Neural Differentiation Unit (NDU), they use minimum amount of blood samples from patients to derive induced pluripotent cells (iPSC) and induced neural stem cells (iNSC). 2D and 3D neural organoid cultures are further developed using the induced stem cells. By using these in vitro models, they investigate the genetic and epigenetic mechanisms of neural development as well as the pathogenesis of neurodegenerative disorders such as ALS and PLS. The unit also provides protocols and trainings to other investigators to derive iPSC and iNSC from patient blood sample or fibroblasts, to differentiate cortical and motor neurons from iPSC and iNSC and to develop 3D brain organoids consisting neuronal, glial and endothelial cells.