大宇李

最近的新闻

教育

Ph.D., University of California, Riverside

课程

• 药物与大脑
• BIOS 3430 Principles of Physiology
• BIOS 4630 Biological Chemistry    

研究兴趣

• Lab: Life Sciences Building 210J

Our main research interest is to understand pathogenic mechanisms underlying neurodegenerative diseases (NDs). 特别是, we are interested in prion-like propagation of pathogenic proteins such as alpha-Synuclein (alpha-Syn) and microtubule associated protein tau (MAPT):

• Cell-to-cell propagation of alpha-Syn: Abundant neuronal protein alpha-Syn is a pathogenic protein to form abnormal protein aggregates, called Lewy body (LB) and causes several NDs including Parkinson's disease (PD) and LB dementia (LBD). Prion-like spreading of alpha-Syn is an exciting new discovery in the progression of NDs. However, there are critical gaps in our understanding of alpha-Syn spreading. We study how alpha-Syn is released, taken up, and thus spreads between neurons. We are particularly interested in alpha-Syn released by neuronal activity as known PD risk factors such as traumatic brain injury (TBI) and sleep deprivation increase neuronal activity and levels of extracellular alpha-Syn. 除了, hyperexcitability and seizures are known to be associated with pathological progression of LBD. Our goal is to study how neuronal subtypes, alpha-Syn突变体, and functional/molecular factors affect pathological transmission of alpha-Syn.
• Mechanisms underlying activity-dependent human tau release: Tau is an intracellular protein but also released to the extracellular fluid. Studies have shown that a prion-like mechanism involving the transfer of hyper-phosphorylated tau between synaptically connected neurons underlies the seeding and spread of tau pathology throughout the brain. 有趣的是, neuronal excitability increases during the early stages of Alzheimer’s Disease (AD) and tau release can be enhanced by the excitability. A better understanding of activity-dependent tau release is a key to uncover mechanisms underlying cell-to-cell propagation of tau and the progression of AD pathology. It is not known the role of phosphorylation in activity-dependent tau release and proteins interacting with tau have yet to be identified for their role in mediating tau release. We have developed a tractable and highly reproducible method of studying activity-dependent tau release in Drosophila primary neuronal culture & 神经肌肉接头, and a human neural progenitor cell line (ReNcell), which form the experimental framework of this study. Optogenetic method has been also used to induce activity-dependent tau release.

其他研究项目:

• Dopamine signaling and Parkinson’s disease: We have studied neurodegenerative and neuroprotective role of dopamine signaling in PD. Dysregulation of dopamine homeostasis causes selective neurodegeneration while activation of D2 receptors is neuroprotective.
• Biogenic amine signaling and olfactory learning: The main goal of this project is to investigate functional role of dopamine and serotonin receptors in synaptic plasticity and olfactory learning. We also study their downstream G-protein signaling mechanisms and the role of DA autoreceptors in modulating excitability and synaptic inputs.

代表的出版物

(Note: * and ** student author(s) from my laboratory: * graduate student, ** undergraduate student)

S. G Ismael *. 辛迪* R.A. 科尔文和D. 李. 2021. Activity-dependent release of phosphorylated human tau from Drosophila neurons in primary culture. Journal of Biological Chemistry 297: 101108.

Ganguly * C. 祁*，J . Bajaj, D .. 李. 2020. Serotonin receptor 5-HT7R in Drosophila mushroom body neurons mediates larval olfactory learning. 科学报告 10: 21267.

J.A. 超视距* * E. 波多尔斯基**和D. 李. 2020. L-DOPA-induced dyskinesia in a genetic Drosophila model of Parkinson’s disease. 经验一般 29(4): 273-284.

气*,年代. 巴尔加* *,S.J. 哦,.J. 李、D. 李. 2017. Optogenetic rescue of locomotor dysfunction and dopaminergic degeneration caused by alpha-Synuclein and EKO Genes. 经验一般 26(2): 97-103.

Wiemerslage*和D. 李. 2016. Quantification of mitochondrial morphology in neurites of dopaminergic neurons using multiple parameters. Journal of Neuroscience Methods 262:56-65.

Wiemerslage *,年代. 伊斯梅尔*和D. 李. 2016. Early alterations of mitochondrial morphology in dopaminergic neurons from Parkinson’s disease-like pathology and time-dependent neuroprotection with D2 receptor activation. 线粒体 30: 138-147.

李. 2015. Global and local missions of cAMP signaling in neural plasticity, learning and memory. 药理学前沿 6:161.

Wiemerslage*和D. 李. 2015. Role of Drosophila calcium channel cacophony in dopaminergic neurodegeneration and neuroprotection. 神经学字母 584:342-346.