帝王会所

Education

Ph.D., University of California, Riverside

Courses Taught

• BIOS 2060 Drugs and the Brain
• BIOS 3430 Principles of Physiology
• BIOS 4630 Biological Chemistry    

Research Interests

• Lab: Life Sciences Building 210J

Our main research interest is to understand pathogenic mechanisms underlying neurodegenerative diseases (NDs). In particular, 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. In addition, hyperexcitability and seizures are known to be associated with pathological progression of LBD. Our goal is to study how neuronal subtypes, alpha-Syn mutants, 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. Interestingly, neuronal excitability increases during the early stages of Alzheimer鈥檚 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 & neuromuscular junction, 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.

Other research projects:

• Dopamine signaling and Parkinson鈥檚 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.

Representative Publications

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

S. Ismael*, G. Sindi*, R.A. Colvin and D. Lee. 2021. Activity-dependent release of phosphorylated human tau from Drosophila neurons in primary culture. Journal of Biological Chemistry 297: 101108.

Ganguly*, C. Qi*, J Bajaj and D. Lee. 2020. Serotonin receptor 5-HT7R in Drosophila mushroom body neurons mediates larval olfactory learning. Scientific Reports 10: 21267.

J.A. Blosser**, E. Podolsky** and D. Lee. 2020. L-DOPA-induced dyskinesia in a genetic Drosophila model of Parkinson鈥檚 disease. Exp Neurobiol 29(4): 273-284.

Qi*, S. Varga**, S.J. Oh, C.J. Lee, and D. Lee. 2017. Optogenetic rescue of locomotor dysfunction and dopaminergic degeneration caused by alpha-Synuclein and EKO Genes. Exp Neurobiol 26(2): 97-103.

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

Wiemerslage*, S. Ismael* and D. Lee. 2016. Early alterations of mitochondrial morphology in dopaminergic neurons from Parkinson鈥檚 disease-like pathology and time-dependent neuroprotection with D2 receptor activation. Mitochondrion 30: 138-147.

Lee. 2015. Global and local missions of cAMP signaling in neural plasticity, learning and memory. Frontiers in Pharmacology 6:161.

Wiemerslage* and D. Lee. 2015. Role of Drosophila calcium channel cacophony in dopaminergic neurodegeneration and neuroprotection. Neuroscience Letters 584:342-346.