51ĀŅĀ×

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 Alzheimerā€™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 & 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 Parkinsonā€™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.

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 Parkinsonā€™s 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 Parkinsonā€™s 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.