C.Y. Daniel Lee, PhD

I have had thorough and extensive training on understanding the molecular and cellular basis of pathogenesis of neurodegenerative diseases in my graduate and postdoctoral studies. I received my MS degree from Dr. Hsi-Yuan Yang’s laboratory at the National Taiwan University, studying the cellular reactions of astrocytes in response to traumatic brain injury. My work demonstrated that astrocytes re-express nestin, a marker for embryonic neuronal/astroglial progenitor cells, and re-enter the cell cycle in response to stab wound injury. I completed my PhD training in Dr. Gary Landreth’s laboratory at Case Western Reserve University, focusing on the role of ApoE and microglia in neuroinflammation and the pathogenesis of Alzheimer’s disease. These studies revealed that ApoE promotes the proteolytic degradation of the β-amyloid (Aβ) protein by microglia. This facilitation is mediated by the cholesterol efflux property of ApoE through regulation of the intracellular trafficking of Aβ in microglia. ApoE also reduced fibrillar Aβ-induced microglial M1 activation. 

After graduating, I joined Dr. X. William Yang’s laboratory at UCLA, to study the pathogenesis of Huntington’s disease (HD) and Alzheimer’s disease (AD). Relevant to the current proposal, I am studying the role of TREM2 in regulating microglial reactivity in vivo using BAC transgenic mouse models of TREM2 crossed with two AD mouse models. We found that elevating TREM2 gene dosage reprograms microglial responses to the amyloid deposition, ameliorating pathological and behavioral deficits. These significant findings were published in Neuron and highlighted in several reviews and news reports. In addition, I also worked on HD related projects on the role of Huntingtin N17 domain in modulating mutant Huntingtin seeding activities, and genomic profiling of Atm genetic reduction in HD mouse models. I am very productive which is evident from over ten peer- reviewed journal publications, including three first author papers and several co-authored papers in AD research (in Neuron and Science). My work is highly recognized and cited in the AD field.

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